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Javier Avalos
Howard I. Maibach
Chapter 1
Introduction
Javier Avalos and Howard I. Maibach
Chapter 2
Botanical Heritage of Dermatology
Scott A. Norton
SECTION I PHYTODERMATOSES
Chapter 3
Etiology of Adverse Reactions to Plants
Georges Ducombs
Chapter 4
Diagnosis and Patch Testing of Plant Dermatitis
John C. Mitchell and Howard I. Maibach
Chapter 5
Prevention of Allergic Contact Dermatitis to Plants
Hongbo Zhai and Howard I. Maibach
Chapter 6
Phytophotodermatoses
Christopher Roland Lovell
Chapter 7
Phytochemical Procedures
Jean-Pierre Lepoittevin
Chapter 8
Botanical Photoallergy
Ai-Lean Chew and Howard I. Maibach
Chapter 9
Toxic Anacardiaceae
Jere D. Guin, John H. Beaman, and Harold Baer
Chapter 10
Araliaceae
Bjoern M. Hausen
Chapter 11
Asteraceae
Mario Robles, Jan West, Eloy Rodriguez, and Michael Heinrich
Chapter 12
The Pollen Allergens of the Betulaceae
Heimo Breiteneder, Jun Wen, and Otto Scheiner
Chapter 13
Hydrophyllaceae
Manuel Aregullin and Eloy Rodriguez
Chapter 14
Primulaceae
Lars P. Christensen
Chapter 15
Urticaceae
Javier Avalos
Chapter 16
Agavaceae
J. Juan Segura, C. Calzado Flores, and J. Del Valle Cantu
Chapter 17
Algae
Jose G. Camarasa
Chapter 18
Alstroemeriaceae
Lars P. Christensen, Kell Kristiansen, and Marian Ǿrgaard
Chapter 19
Aristolochiaceae
Luisa Pistelli
Chapter 21
Bromeliaceae
Félix Cordoba Alva, Eduardo Pérez-Campos, and Patricia Magaña
Chapter 22
Lichens
Marius Rademaker
Chapter 23
Verbenaceae
Evy Paulsen and Klaus E. Andersen
Chapter 24
Allergic Hardwoods
Bjoern M. Hausen
Chapter 25
Toxicodendron of the Southern Pacific
Marius Rademaker
Chapter 26
Spices
Matti Hannuksela and Aila Niinimaki
CONTENTS
1.1 Plants
1.2 Beneficial Uses of Plants
1.2.1 Herbal Remedies
1.2.2 New Pharmaceuticals
1.2.3 Cosmetic Products
1.3 Adverse Occurrences
1.3.1 Contact Urticaria
1.3.2 Phytophotodermatitis
1.3.3 Irritant Contact Dermatitis
1.3.4 Allergic Contact Dermititis
1.4 Identification of Active Components
1.5 Summary
1.6 References
1.1 PLANTS
The plant kingdom is a critical component to man’s existence. Plants provide the basic energy
source to sustain life on this planet. Many researchers have devoted their lives to understand better
every aspect of the plant. Their efforts are evident in the thousands of literature reports that have
been published emphasizing the nutritional, medicinal, and detrimental properties of plants. Over
the years, man has adapted to its plant world and the plant in turn has been forced to evolve with
man. As a result, plants have developed intricate metabolic pathways that can generate unique and
biologically active natural products.
The focus of this book is to describe the biological activity of plants, some of their beneficial
uses, and most importantly, understand the types of adverse reactions associated with plant contact
in order to prevent re-exposure. The second chapter of this book accentuates the beneficial properties
of plants. The first section of the book describes the etiology of adverse reaction to plants and
discusses preventive methods of plant dermatitis. Clinical and botanical investigations are depicted
in the second section of the book. The major emphasis of this book, sections 3, 4, and 5, is on the
adverse properties reported with several plant families.
1.3.2 PHYTOPHOTODERMATITIS
Phytophotodermatitis occurs when the skin is exposed to sunlight after contact with an offending
plant; reactions are erythema, pruritus, vesiculation after 1 to 2 days of plant contact, and subsequent
hyperpigmentation. The common culprit plant families are the Apiaceae (Umbelliferae), Rutaceae,
and Moraceae. Some of the common names of the plants involved for the Apiaceae family are
Queen Anne’s lace, cow parsnip, celery, srping parsley, parsnip, and giant Russian hogweed.4 For
Rutaceae, these are the bergamot lime, burning bush, and gas plant. Figs are the culprit in the
family Moraceae. St. John’s Wort (family Hypericaceae) has also been implicated. The most
common phototoxic compounds are the furocoumarins (e.g., psoralen, 8-methoxypsoralen, and
5-methoxypsoralen).
1.5 SUMMARY
The identification of plants and their detrimental constituents is a challenging task. Our hope is to
introduce the reader to the intricacy of plant defenses: the generation of unique, biologically active
secondary metabolites or specialized appendages. In addition, the reader will become acquainted
1.6 REFERENCES
1. Mitchell, J. and Rook, A., Botanical Dermatology: Plants and Plant Products Injurious to the Skin,
Greengrass, Vancouver, BC, 1979.
2. Von Krogh, G. and Maibach, H. I., The contact uriticaria syndrome—an updated review, J. Am. Acad.
Dermatol., 5, 328, 1981.
3. McGovern, T. W. and Barkley, T. M., Botanical dermatology, Int. J. Dermatol., 37, 321, 1998.
4. Johnson, B. E., Phototoxic reactions, in Plants and the Skin, Lovell, C. R., Ed., Blackwell Scientific,
Oxford, 1993, 66.
5. Lovell, C. R., Irritant plants, in Plants and the Skin, Lovell, C. R., Ed., Blackwell Scientific, Oxford,
1993, 42.
6. Dupuis, G. and Benezra, C., Allergic Contact Dermatitis to Simple Chemicals: A Molecular Approach,
Marcel Dekker, NY, 1982.
7. Polak, L., Immunological aspects of contact sensitivity. An experimental study, in Monographs in
Allergy, Vol. 15, S. Karger, Basel, 1980.
CONTENTS
2.1 Introduction
2.2 Natural Products and Ethnobotany
2.3 Literature on Botanical Dermatology
2.4 Plants and the Skin
2.5 Examples of Plants in Dermatologic Therapy
2.6 Examples of Plants in Dermatologic Diagnosis
2.7 Other Natural Products in Dermatology
2.8 The Future of Natural Products in Dermatology
2.9 Herbal Medicines, Botaniceuticals, and Entrepreneurs
2.10 Conservation, Biodiversity, and Preservation of Indigenous Cultures
2.11 References
Along the bank of the river … will grow all kinds of trees [whose] fruit will be used for food and their
leaves for medicine. Ezekiel 47:12
2.1 INTRODUCTION
Dermatologic Botany addresses mainly the harmful or injurious effects of plants upon the skin.
This chapter serves to remind readers of the beneficent role of plants in dermatology (and medicine
in general) throughout history. Many of my patients and colleagues know of my interest in botany
and often ask if I use (or believe in) herbal medicines or medicinal plants. The short answer is,
“Of course, but maybe not as you think.” The full answer, a discourse on the historical and
continuing harmonious relationship between plants and dermatology, constitutes this chapter.
The disciplines of medicine and botany have been closely allied through most of man’s history.
For millennia, healers depended on the helpful properties of plants and were, by necessity, accom-
plished botanists.1,2 For centuries, herbals (manuals of pharmacognosy in which the therapeutic
properties of plants are cataloged) served as the standard treatises of Western medicine. Healers in
both Western and non-Western models of medicine relied—and still rely—on medicinal plants. In
developing nations, approximately 80 percent of the populations are still treated with traditional
medicines made from natural products with little or no processing.3 From 1959 to 1980, medications
derived from vascular plants account for one fourth of all out-patient prescriptions in the United
States.3 Since 1980, roughly one-half of the medications submitted to the FDA were derived from
natural products.4
* The opinions and assertions contained herein are those of the author and not necessarily those of the Department of Defense.
In those days Hezekiah was sick and near death … . Then Isaiah said, “Let them take a lump of figs
and apply it as a poultice on the boil, and he shall recover.” Isaiah 38:21
CONTENTS
3.1 Introduction
3.2 Clinical Aspects
3.2.1 Irritant Contact Dermatitis
3.2.1.1 Mechanical Causes
3.2.1.2 Chemical Causes
3.2.2 Allergic Contact Eczema
3.2.3 Phototoxic Dermatitis
3.2.4 Photoallergic Dermatitis
3.2.5 Contact Urticaria
3.2.6 Erythema-Multiform-Like Eruptions
3.3 Important Plant Species
3.3.1 Alliaceae
3.3.2 Alstromeriaceae
3.3.3 Amaryllidaceae
3.3.3.1 Tulipa gesneriana L
3.3.4 Anacardiaceae
3.3.5 Asteraceae (Compositae)
3.3.5.1 A Panorama of Contact Dermatitis Owing to Compositae
(Asteraceae)
3.3.5.1.1 Ambrosia p.p. or Ragweed
3.3.5.1.2 Anthemis Species
3.3.5.1.3 Arnica p.p. Species
3.3.5.1.4 Artemisia p.p. Species
3.3.5.1.5 Chrysanthemum p.p. Species
3.3.5.1.6 Cichorium p.p. Species
3.3.5.1.7 Cynara p.p. Species
3.3.5.1.8 Dahlia Variabilis (Willd) Desf., Dahlia
3.3.5.1.9 Inula helenium L.
3.3.5.1.10 Lactuca sativa L., Lettuce
3.3.5.1.11 Parthenum hysterophorus
3.3.5.1.12 Saussurea costus
3.3.5.1.13 Miscellanenous Contact Dermatitis Causing Asteraceae
3.3.6 Primulaceae
3.3.7 Ginkgoaceae
3.3.8 Lichens
3.3.9 Liverworts
3.1 INTRODUCTION
It is difficult to evaluate the frequency of phytodermatosis. In Sweden, 1752 patients suffering from
professional dermatosis were systematically tested with vegetal allergens: 8 percent of women and
6 percent of men reacted positive to one or more of them.1 Nevertheless, the investigation did not
enable us to understand the relevance of these positive tests compared with the clinical history of
each patient tested. We can state, nonetheless, that these positive results were irrelevant with regard
to the clinical history of the patients.
Dermatosis of plant origin are attributable to different mechanisms. They may be owing to a
contact irritation or allergic reaction. The simultaneous exposure to sun and plants can lead to a
phototoxic or a photoallergic reaction. These dermatoses occur when there is a direct contact with
the plant, a part of it, or even with an extract (industrial product, pharmaceutical, or cosmetic). The
patients more at risk are florists, farmers, gardeners, foresters, and wood-workers. A simple walk
or leisure activities in the forest (shooting, fishing, many sports) may be risky.
The shape of the plants could in itself explain some of the problems caused by contact. Prickly
and cutting-leafed plants can lacerate the skin and leave wounds and many scratches. Cactus
wounds, for example, may cause secondary infections. The bristles and barbs (trichomes and
glochides) of some plants and their leaves, stems, and seeds often have a pointed and stinging
composition that can provoke papules, prurigo, and urticaria by penetrating the skin. These tri-
chomes may even break down and remain in the skin which creates foreign body granulomes.
Cutaneous plant reactions are mostly of a chemical nature. Acids (acetic, citric, formic, malic, and
oxalic), glucosides, and proteolic enzymes are frequently responsible for the irritation (lemon juice,
onions, hyacinth, and tulip). Urticant reactions and even edematous stomatitis can occur with people
who have handled or chewed by mistake the leaves of Diffenbachia: the crystals of oxalate contained
by the plant can provoke a massive, rapid, and acute irritation, within a few hours, sometimes less.
Chronic irritation occurs with repeated contact with the irritant factor or on skin already affected.
3.3.1 ALLIACEAE
Allium sativum L., garlic, is used in cooking, folk medicine, and pharmaceutical products. The first
dermatitis dates from 1950 by Edelstein concerning dermatitis on the wrist of a meatmincer
operator.5 Garlic is a contact sensitizer, but Bursk does not exclude an irritant potential.6 In Portugal,
garlic is a common cause of pulpitis.7 Bursk6 quoted cross sensitization between garlic and onion,
but Bleumink and Nater8 have since questioned the authenticity of cross-reaction between garlic,
onion, and tulip bulbs, or any other Liliaceae. Papageorgiou et al. have identified the allergen and
tested diallyldisulphide in man and the guinea pig.9
3.3.2 ALSTROEMERIACEAE
This family was formerly classified with the Amaryllidiaceae. Species most frequently involved
include: Alstroemeria aurantica Don (syn. A. aurea) and A. ligtu L.
Alstroemeria hybrids are increasingly popular in the cut-flower trade. Horticulturists and florists
are at risk of both irritant and allergic contact dermatitis. Handling of cut flowers provokes a
dermatitis affecting mainly the fingertips that is similar to tulip fingers. Björker described the case
3.3.3 AMARYLLIDACEAE
Narcissus sp., narcissus, jonquil, daffodil, and so on, native to central Europe, the Mediterranean,
and Asia, are extensively cultivated, especially Narcissus pseudonarcissus L., N. jonquilla L.,
and N. poeticus L. Lily rash owing to the narcissus species is regularly observed in gardeners,
bulb sorters, plant growers, and florists.13 Gude et al. identified in N. pseudonarcissus L. two
fractions capable of inducing hypersensitivity in animals (masonin and homolycorin acted as
elicitors).14
Garden tulips are derived from an unknown hybrid complex. The numerous different forms and
varieties have been obtained by selection and crossing of existing hybrids. Dermatitis among bulb
handlers and florists is an important and common hazard for tulip growers. Irritant and allergic
contact dermatitis occurs. Bulb sorters, packers, and collectors develop a characteristic dermatitis
called tulip fingers: a painful, dry, fissured hyperkeratotic eczema, at first underneath the true margin
of the nails and periungual region.13 Sometimes an irritable dermatitis spreads to the face, hands,
forearms, and genital region. Tulip fingers is common in Holland and in other parts of Europe. The
majority of the allergen is found in the epidermis of the bulb, but contact dermatitis is also possible
from handling cut flowers.
The allergen responsible for tulip dermatitis has been shown to be a glucose derivative tuliposide
A that gives (by enzymatic or acid-catalyzed hydrolysis) tulipalin A, D-methylen-J-butyrolactone).
Tulips contain a second glucoside, tuliposide B. Slob reported that patients sensitive to tulip react
to tuliposide A and tulipalin A but not to tulipalin B.15 However, Barbier and Benezra have shown
that E-hydroxy-D-methylen-J-butyrolactone is sensitizing in guinea pigs and cross-reacts with
unsubstituted tulipalins.16
Patch testing can be performed with the epidermis of the bulb. Hjorth recommended extracts
of the variety Apernoon. Bleumink and Nater reported cross-reaction between onion, garlic, and
tulip bulbs. True cross sensitization does not seem to be proven.17
3.3.4 ANACARDIACEAE
This family includes 600 species in its 60 genera and is probably more the cause of dermatitis than
all of the other plant families combined. Among members of this family, certain ones have an
economic importance as foods, drugs, oils, resins, varnishes, dyes, tans, and so on. Most occur
naturally in the tropical regions; some species occur in the Mediterranean regions, in eastern Asia,
and in America. They are cultivated in botanical gardens, and some even in private gardens.
The taxonomy of Anacardiaceae is difficult and confused. A new classification considers the
species Rhus toxicodendron within a genus Toxicodendron. There are numerous synonyms for each
species.
3.3.6 PRIMULACEAE
This family has a cosmopolitan distribution. It is especially found in north temperate regions.
Primula is the more representative genus.
Primula obconica Hance., goblet-primrose, native to China, is very popular in Europe because
of its beauty, long flowering season and resilience.
Primula sinensis (Lindl) Sabine, Chinese primrose, is distinct from P. obconica Hance. Hjorth
reviewed primula dermatitis in Mitchell and Rook.68 The eyelids, face, neck, fingers, hands, and
arms are most often affected. P. obconica can also provoke conjunctivitis and an erythema-multi-
form-like eruption. The most important allergen is primin, a quinone present in the plant in highest
concentration from April to August.69 For Cairns, it is not certain that primin is the sole allergen.70
Fresh leaves can be used for patch testing. Agrup et al. proposed an extract of stem and leaves
harvested in spring. Synthetic primin is now available commercially.71 It is a powerful allergen
which must be tested at extremely low concentration (0.01 percent pet.) to avoid inducing sensiti-
zation. Fernandez de Corres observed active sensitization in 5 of 20 patients retested several months
later, after using an ether extract for patch testing.72
3.3.7 GINKGOACEAE
Ginkgo biloba L., ginkgo or ginkgo tree, is the sole survivor of the Ginkgoaceae order and can be
considered the world’s oldest living tree. Contact dermatitis from ginkgo tree fruit has been reported
in the area where female ginkgo trees grow. The ginkgo fruit is used in cooking and the children
play “marbles” with the fallen fruit. Lepoitevin et al. reported a study in guinea pigs tested with
anacardic acid and urushiol; no clear cross-reactions were observed.73
Sowers et al. reported a small epidemic of contact dermatitis among the students (35 cases) of
a preparatory school for girls, owing to contact with trampled fruit pods splashed onto the legs.74
Nakamura reported four cases with a history of contact dermatitis from ginkgo.75 Tombe et al.
reported three cases occurring in Strasbourg among Asiatic immigrants.76 Allergic reactions occur
only when the fruit is opened and the pulp extracted. The lesions consist of erythematous papules
and vesicles, with swelling in the more severe cases, affecting the face, forearms, and thighs.
Contact dermatitis can also involve the penis and scrotum.77 Ingestion of ginkgo fruit provokes
stomatitis, cheilitis, and proctitis. Becker and Skipworth recommended patch tests with fruit pulp
in 1 percent in acetone.78 Cross-reaction is possible between ginkgo fruit pulp and poison ivy, and
also between ginkgo and cashew nut.
3.3.8 LICHENS
Lichens as a class belong to the Thallophytes division. Lichens consist of a fungus and an alga in
symbiosis. Lichens are cosmopolitan and grow on walls, roofs, tree trunks, and rocks. Several species
are sensitizing. Champion described immediate allergy (asthma and urticaria) by inhalation or direct
3.3.9 LIVERWORTS
The bryophites division comprises the Hepaticae class and Musci class (mosses). Among Hepaticae,
the order Jungermannilales comprises numerous families including Frullaniaceae.
Frullania dilatata (L.) Dum., Frullania tamarisci (L.) Dum., and F. tamarisci (L.) Dum. ss.
niqualensis, are the most aggressive species. Mitchell et al. listed 12 species in British Columbia:
only one gave a negative patch test.86 Frullania species grow on the trunk and branches of trees
(oak, beech, locust tree, poplar, etc.) and rocks. Suire and Ducombs described the method of
microscopic examination to identify the Frullania species.87
Le Coulant and Lopez first described the role of liverworts in forestry sensitization.88 Contact
dermatitis affects exposed areas of the face, neck, hands, forearms, and genitals. Sometimes
dermatitis can be generalized. Sometimes the eruption seems to be aggravated by sunlight. The
plant contains sesquiterpene lactones, among them (+) frullanolide was identified in F-dilatata (L.)
Dum., and (-) frullanolide in F. tamarisci(L.) Dum.89 Barbier and Benezra demonstrated the
stereospecificity of sensitization to one enantiomer in guinea pigs. Animals sensitized to the (+)
frullanolide do not cross-react to its mirror image (-) frullanolide and vice versa.90 Reactions to
both enantiomers in man can been explained by multiple concomitant sensitizations.91 On the other
hand, cross-reactions have been demonstrated between the sesquiterpene lactones of Laurus nobilis
L. (laurel) and Frullania.92,93
3.3.10 WOODS
3.3.10.1 Native Woods
Most of the literature on dermatosis due to wood gives greater emphasis to the importance of exotic
or foreign woods, with less mention of native woods as causes of allergic contact dermatitis. Weber
reported cutaneous sensitizations among forestry workers.94 Acacia, alder, ash, beech, birch, and
poplar are incriminated. Other trades, such as carpenters, joiners, cabinetmakers, polishers and
finishers, can be involved. It must be always be borne in mind that patients can also be in contact
with lichens or liverworts growing on the bark of trees. The mechanism of dermatitis owing to
wood can be irritant or allergic. Airborne contact dermatitis is possible with pollens borne by the
wind and also in joiners workshops from sawdust. Contact dermatitis begins on the dorsa of the
hands and forearms, eyelids, face, and neck, as well as the genitals. The scalp can be affected in
bald men. If the clothing gives poor protection, fine dust may drift inside and eczema involve the
sweaty areas of the axillae, waistband, groin, ankles, and dorsa of the feet.95 In Europe, two species
are the most often quoted: Piceae and Pinus.
Hublet et al.,110 Oleffe at al.,111 Woods and Calnan,112 Cronin,113 Hausen,114 and Benezra et al.115
list and describe, with numerous references, irritation and allergy provoked by tropical woods. In
this book, Hausen also describes these effects. The skin can be damaged by the mechanical action
of bristles and splinters, by chemical irritation or sensitization, or by combinations of these
processes. Photosensitization has not been proven but may well occur in the Rutaceae and
Flindersiaceae.
The dermatitis resembles an airborne dermatitis and begins on the dorsa of the hands and
forearms, affecting the eyelids, face, and neck, as well as the genitals. Contact dermatitis affects
sawyers, carpenters and joiners, and polishers and finishers exposed to fine dust. Dermatitis from
the solid wood of finished articles is much less common, but prolonged contact with musical
instruments, bracelets, or knife handles made of rosewood can be followed by eczema. An erythema-
multiform-like reaction has also been described. Sawdust exposure can also provoke irritation of
mucous membranes, contact urticaria, nasal irritation, allergic rhinitis, conjunctivitis, systemic
syndromes, and asthma. Certain fine dusts from these woods are also responsible for nasal and
ethmoid cancers, specially in poorly ventilated workshops. Patch tests can be performed with
sawdust or extracts, or allergens when these are available.
3.3.10.2.1 Bignoniaceae
This family comprises wood sensitizing owing to the presence of quinones (lapachone, lapachol,
etc.). Peroba do campos [Paratecoma peroba (Record) Kuhlm.] and Lapacho wood [Tabebuia
avellanedae (Griseb.) Lor.] provoke eczema from contact with sawdust. See Chapter 20 by Binutu
and Cordell on Bignoniaceae.
3.3.10.2.2 Cupressaceae
Sawdust of the western (Canadian) red cedar (Thuya plicata D-Don.) causes respiratory symptoms
and contact dermatitis in wood workers. The red cedar is used for indoor and outdoor furnishings.
Thuya plicata D. Don. contains E-thujaplicin and 7-hydroxy-4-isopropyltropolone, giving pos-
itive patch tests. Reactions were also observed with thymoquinone and methylbenzoquinone.
3.3.10.2.3 Fabaceae (Papilionaceae)
Bowdichia nitida spruce, Sucupira, is used for building frameworks and joints, exterior construc-
tions, and railway sleepers. The bark and roots are used in medical products. Sucupira is known
as a sensitizer (quinones: 2,6-dimethoxybenzoquinone and bowdichione). Cross-reactions are pos-
sible with dalbergiones and also Primula.
Dalbergia latifolia Roxb., Dalbergia melanoxylon Guill. and Perr. African blackwood, and
Indian rosewood are woods that are used for making veneers for dining room and bedroom furniture,
desk accessories, walking sticks, paper knives, bracelets, necklaces, mouthpieces for flutes, and
so on.
3.3.10.2.4 Moraceae
Chlorophora excelsa (Welw) Benth and Hook., iroko (African teak), is used for general building
and railway sleepers. Dermatitis affects the hands, face, and eyelids. Chlorophorin is certainly
allergenic and may be used in petrolatum for patch testing, when available. Moist sawdust may
also be used.
3.4 REFERENCES
1. Fregert, S., Occupational dermatitis in 10-years material, Contact Derm., 1, 96, 1975.
2. Oppenhein, M., Dermatitis bulbeuse striée consecutive aux bains de soleil dans les prés, Ann. Derm.
Syph., 5, 1, 1932.
3. Ippen, H., Photodermatitis bullosa generalisata, Derm. Beruf umwelt, 32, 115, 1984.
4. Pathak, M. A, Daniels, F., and Fitzpatrick, T. B., The presently known distribution of furocoumarins
(psoralens) in plants, J. Invest. Dermatol., 39, 225, 1962.
5. Edelstein, A. J., Dermatitis caused by garlic, Arch. Derm., 61, 111, 1950.
6. Bursk, J. W., Classic aspect of onion and garlic dermatitis in housewives, Ann. Allerg., 12, 592, 1954.
7. Brandâo, F. M., Dermatite de contacto pelo alho, Trab. Soc. Post Dermatol. venereol. Ano, 35, 27, 1977.
8. Bleumink, E. and Nater, J. P., Contact dermatitis due to garlic cross-reactivity between garlic, onion,
and tulip, Arch. Dermatol. Forsch., 274, 117, 1973.
CONTENTS
4.1 Introduction
4.2 Plant Samples
4.3 Identification
4.4 Value of Literature Search
4.5 Lack of a Diagnostic Test for Phytophoto-Toxic (Irritant) Dermatitis:
Plant Test vs. Patient Test
4.5.1 Photopatch Testing
4.5.2 Lack of Significant Patch Test in Suspect Poison Ivy–Oak Dermatitis
4.5.3 Patch Testing to Plants
4.6 Housecall and Garden Walk
4.7 Phytochemical Investigation
4.8 References
4.1 INTRODUCTION
We have often been asked for guidance by colleagues during their investigation of suspected plant
dermatitis, but a partial follow-up suggests that such investigations are not often brought to a
successful conclusion. Why is this so?
A difficulty in the investigation of phytodermatitis is that speed is necessary to achieve a
satisfactory result. In many instances, by the time the clinician is ready to perform testing, the
patient is no longer afflicted and has lost interest. The patient is only too glad to forget the whole
episode leaving the investigator, who is about to make a sparkling, maybe original finding, frustrated.
This experience deters some from further aspirations in botanical study and, consequently, some
interesting observations are not shared.
4.3 IDENTIFICATION
It is essential for meaningful scientific investigation of plant dermatitis that botanical names be
used. A colloquial or common name has no scientific validity and is useless for scientific reports.
Colloquial names for a plant species vary from one country to another and are misleading and
numerous. It is essential to have botanical identification by a taxonomist. A local nurseryman is
not recommended, but somewhere in each community is located a botanist who can provide what
is needed.
The challenge is to find this individual—try a botanical garden or a botanical department at a
college or university. Botanists are as subspecialized as we are, some interested in biochemistry,
plant physiology, and so on. We need the one who can provide a botanical name for a common
weed or garden specimen. This superior person will be glad to help but, when needed, may be off
plant collecting on the Himalayas or in Amazonia. We suggest that more than one authority be sought.
A botanical name permits a scientific literature search, the important next step. Refer to standard
sources such as those by Benezra et al.,1 Hausen,2 Lovell,3 or Mitchell and Rook.4 Is the named
plant reported to cause dermatitis or to contain psoralen? Is the plant a known irritant such as
Euphorbia?
4.8 REFERENCES
1. Benezra, C., Ducombs, G., Sell, Y., and Foussereau, J., Plant Contact Dermatitis, Decker, Toronto,
1985.
2. Hausen, B. M., Allergiepflanzen-Pflanzenallergene: Handbuch und Atlas der allergie-induzierenden
Wild- und Kulturpflanzen, Ecomed Verlagsgesellschaft mbH, Landsberg/München, 1988.
3. Lovell, C., Plants and the Skin, Blackwell, London, 1993.
4. Mitchell, J. C. and Rook, A., Botanical Dermatology, Greengrass, Vancouver, 1979.
5. Kerner, J., Mitchell, J. C., and Maibach, H. I., Irritant contact dermatitis from Agave americana L.,
Arch. Dermatol., 108, 102, 1973.
6. Daniels, F. A., A simple microbiological method for demonstrating phototoxic compounds, J. Invest.
Dermatol., 44, 259, 1965.
7. Marzulli, F. and Maibach, H. I., Dermatotoxicology, 4th ed., Hemisphere Press, Washington, D.C.,
1991.
8. Rougier, O., Goldberg, A., and Maibach, H., In Vitro Skin Toxicology, Lieberg, NY, 1994.
9. Rostenberg, A., Jr., An anecdotal biographical history of poison ivy, Arch. Dermatol., 72, 438, 1955.
10. Matthew 25:1.
CONTENTS
5.1 Introduction
5.2 Plant Dermatitis
5.2.1 Immediate Contact Dermatitis (Urticaria)
5.2.2 Irritant Contact Dermatitis
5.2.3 Phytophotodermatitis (Photoirritation, Phototoxicity)
5.2.4 Allergic Contact Dermatitis
5.3 Prevention
5.3.1 Generic Prophylactics
5.3.2 Role of Hyposensitization
5.3.3 Protective Creams and Ointments
5.4 Conclusions
5.5 References
5.1 INTRODUCTION
Allergic contact dermatitis to plants is a significant problem worldwide. Poison ivy and poison oak
dermatitis, a typical plant allergic contact dermatitis, affects millions yearly.1-5 The severity of plant-
induced contact dermatitis not only depends on the plant’s irritant or allergic potential but also the
degree of exposure and the sensitivity of the individual. Even plants which rarely cause contact
dermatitis may produce severe eruptions in highly allergic patients.6
Avoiding such causative plants may not be practical for persons whose occupation or recre-
ational activities are outdoors, such as forest fire fighters, utility line workers, agricultural workers,
gardeners, outdoor enthusiasts, and so on. Therefore, prevention approaches play a critical role in
reducing the risk of developing allergic contact dermatitis to plants. Numerous articles have been
written on the prevention of allergic contact dermatitis to plants. Prevention by immunologic
modification through oral or parenteral hyposensitization is possible but not widely employed.1,2,6,7
Protective creams (or barrier creams) decrease such dermatitis.3-5,8,9 This chapter highlights the
personal prevention of allergic contact dermatitis to plants and, in particular, emphasizes the results
of recent studies.
5.3 PREVENTION
5.3.1 GENERIC PROPHYLACTICS
The allergic component of the plant is so rapidly absorbed through the skin that highly sensitive
people must remove the antigen within minutes of exposure. Vigorously washing the skin with
water and soap are essential, but an organic solvent might be beneficial if done immediately.2,6,7
Rubber gloves may not protect the individual because the allergens can penetrate the rubber gloves
and produce dermatitis.2,6,7,12 Heavy-duty vinyl and cloth gloves may afford some protection.
Protective clothing limits contact with the allergen but may itself be a source of exposure if items
are not removed and cleaned with care.1,6,7 Wahlberg and Maibach12 summarized this field.
FIGURE 5.3 Plot of mean reaction scores for quaternium-18 bentonite (Q18B) and control sites. (From Marks
et al., J. Am. Acad. Dermatol., 33, 212, 1995. With permission.)
Toxicodendron extract then was placed on the center of each target area and covered with a Finn
Chamber for 4 h. Assessment of Toxicodendron dermatitis was followed on days 1, 2, 3, 4, and 7
after application. The barrier creams Stokogard, Hollister Moisture Barrier, and Hydropel signifi-
cantly reduced the erythema, induration, and global severity of Toxicodendron dermatitis
(Figure 5.2).
Marks et al.5 investigated the effect of 5 percent quaternium-18 bentonite lotion in preventing
experimentally induced poison ivy and poison oak allergic contact dermatitis in 211 susceptible
volunteers. It was a single-blind, paired comparison, randomized, multicenter study. Both forearms
were patch tested with urushiol 1 h after applying the test lotion on one randomly selected forearm.
All test materials were removed 4 h later and the sites interpreted for reaction 2, 5, and 8 days
later. Results shown that the test sites pretreated with quaternium-18 bentonite lotion had absent
or significantly reduced reactions to the urushiol compared with untreated control sites (Figure 5.3).
Zhai et al.9 utilized an in vivo human model to examine the effect of potential protective
materials against two acute primary irritants (SLS and NH4OH plus urea) and one allergen (Rhus).
The putative protective materials and vehicle were applied to both ventral forearms of 10 subjects
in each group according to a randomized code. Test materials were spread over a marked 2.0 cm2
area, massaged in, allowed to dry for 30 min, and reapplied with another 30 min drying period.
The model irritants and allergen were then applied (0.025 ml) to an AL-test® occlusive patch that
in turn, was placed for 24 hours over each of the 8 designated sites. Inflammation was scored
according to a clinical scale 72 h post application. Paraffin wax in cetyl alcohol significantly
(p<0.01) decreased Rhus allergic contact dermatitis (Figure 5.4).
5.5 REFERENCES
1. Epstein, W. L., Occupational poison ivy and oak dermatitis, Dermatol. Clin., 12, 511, 1994.
2. Fisher, A. A., Poison ivy/oak dermatitis. Part I: Prevention—soap and water, topical barriers, hyposen-
sitization, Cutis, 57, 384, 1996.
3. Orchard, S., Fellman, J. H., and Storrs, F. J., Poison ivy/oak dermatitis. Use of polyamine salts of a
linoleic acid dimer for topical prophylaxis, Arch. Dermatol., 122, 783, 1986.
4. Grevelink, S. A., Murrell, D. F., and Olsen, E. A., Effectiveness of various barrier preparations in
preventing and/or ameliorating experimentally produced Toxicodendron dermatitis, J. Am. Acad.
Dermatol., 27, 182, 1992.
5. Marks, J. G., Jr., Fowler, J. F., Jr., Sherertz, E., and Rietschel, R. L., Prevention of poison ivy and
poison oak allergic contact dermatitis by quaternium-18 bentonite, J. Am. Acad. Dermatol., 33, 212,
1995.
6. Guin, J. D., Plant dermatitis, in Practical Contact Dermatitis, Guin, J. D., Ed., McGraw-Hill, New
York, 1995, 497.
7. Juckett, G., Plant dermatitis, Postgrad. Med., 100, 159, 1996.
8. Epstein, W. L., Topical prevention of poison ivy/oak dermatitis, Arch. Dermatol., 125, 499, 1989.
9. Zhai, H., Willard, P., and Maibach, H. I., Evaluating protective materials against irritants and allergens:
an in vivo screening human model, Contact Derm., submitted, 1998.
10. Lahti, A., Nonimmunologic contact urticaria, in Contact Urticaria Syndrome, Amin, S., Lahti, A., and
Maibach, H. I., Eds., CRC Press, Boca Raton, FL, 1997, 5.
11. Amin, S. and Maibach, H. I., Immunologic contact urticaria definition, in Contact Urticaria Syndrome,
Amin, S., Lahti, A., and Maibach, H. I., Eds., CRC Press, Boca Raton, FL, 1997, 11.
12. Wahlberg, J. E. and Maibach, H. I., Prevention of contact dermatitis, in Protective Gloves for Occu-
pational Use, Mellström, G. A., Wahlberg, J. E., and Maibach, H. I., Eds., CRC Press, Boca Raton,
FL, 1994, 7.
CONTENTS
OCH3
O O
psoralen
OCH3
O O O
8-methoxypsoralen
O O O
5-methoxypsoralen
OCH3
O O O
5,6-dimethoxyisopsoralen
H3CO
OCH3
FIGURE 6.3 The major phototoxic psoralens, psoralen, 8-methyoxypsoralen, 5-methoxypsoralen, and
5,6-dimethoxyisopsoralen.
sphondin
O O O
H3CO
O O O
OCH3
Gardeners are clearly at risk, chiefly from rue (Ruta graveolens) and (in the United States)
from the burning bush (Dictamnus albus). Modern power tools such as string trimmers (Figure 6.8)
are used to trim areas of scrub and rank weeks; unfortunately, these tools deliver a buckshot spray17
of plant sap to the skin. The scantily clad operator develops bright red irregular macules and papules
on the anterior chest wall and arms within 12–24 h of exposure, the so-called strimmer dermatitis18
or weed-wacker’s dermatitis.19 The eruption may superficially resemble pityriasis lichenoides,
although its distribution is distinct (Figure 6.9). Histology reveals a dermal capillaritis with a
pericapillary lymphocytic infiltrate.19 Garlands containing fruit capsules of Pelea anisata have
induced bullous phototoxic reactions, particularly when the garlands (lei) are worn for the celebra-
tion of Kamehameha Day in early June in Hawaii.20 Laboratory workers handling psoralen-con-
taining materials may develop bullae following spillage.21 Similarly, operatives harvesting or can-
ning vegetables such as celery and parsnip are at risk of phototoxic reactions.22
The term berlock (breloque) dermatitis (Figure 6.10) was first coined by Rosenthal in 192523
taking its name from the German work berlock, meaning a charm or trinket (breloque in French).
The pendant-like streaks of hyperpigmentation10 occur on the neck, face, arms, or trunk in areas
of light exposure and were subsequently attributed to psoralens in bergamot oil that was derived
from the rind of Citrus bergamia fruit. Many cases were described subsequently, although it has
become much rarer since the introduction of artificial bergamot oil.24 In a recent Italian survey,
bergamot oil is still implicated in patients with photodermatitis.25 It has been used as a suntanning
agent for many years. Phototoxicity has followed its use in aromatherapy26,27 and the use of lemon
oil in a sauna room.28 Both oils are rich in 5-methoxypsoralen.
Patients receiving PUVA therapy either ingest psoralens or apply them topically before exposure
to UVA. Toxic reactions occur due to overdosage with psoralen or UVA or accidental exposure to
additional UVA, for example, from a sunbed or natural sun. Topical application of psoralens is
more likely to induce phototoxic reactions.29 Second degree skin burns have been reported in two
women who received PUVA.30
Ingestion of plant material is an important cause of phototoxic reactions in animals. Several
naturally occurring molecules, such as icterogenic and rehmannic acid, induce cholestasis prevent-
ing the excretion of phylloerythrin, a porphyrin metabolite of chlorophyll.31 Other plant pigments,
including hypericin, are direct causes of photosensitivity.32 Similarly, phototoxicity has been
reported in five Japanese who ingested a preparation containing the alga Chlorella as a natural
health food! The photosensitiser appears to be a chlorophyll derivative, pheophorbide A.33 Recent
case reports confirm that ingestion of vegetables rich in psoralens is capable of inducing phototox-
icity in individuals who subsequently lie under UVA sunbeds.34-36 Sunbed exposure can also induce
phototoxic reactions in individuals who handle vegetables such as parsnips.37
TABLE 6.2
Phototoxicity: ‘At Risk’ Activities
Gardening – brushing against plants, e.g, rue, Dictamnus
– harvesting vegetables, e.g., parsnip or fruits, e.g., figs
– using string trimmers
Rambling/jogging/rolling in the hay
Play – making pea shooters, fighting with vegetables
Swimming
Canning or processing vegetables
Medication – use of rue as insect repellent
– PUVA toxicity
Cosmetic – tan promoters
– breloque/berlock reactions from cosmetics
– wearing lei/garlands of Pelea anisata
Ingestion – chlorella
– psoralen-rich foods
FIGURE 6.9 String trimmer dermatitis; lesions are restricted to areas of light exposure and contact with plant
sap (typically, the back is spared).
Rutaceae Dictamnus albus Burning bush, gas plant Mediterranean; a popular border plant in
(continued) United States (Reference 16)
Pelea anisata Mokihana Hawaii (Reference 20)
Phlebalium argenteum Blister plant Western Australia, cultivated in California
Ruta graveolens Rue Mediterranean, cultivated herb; important
cause of phototoxicity (Reference 42)
Ruta chalepensis
Ruta corsica Endemic to Corsica, Sardinia (Reference 43)
Algae Chlorella spp Ingestion in Japan (Reference 33)
planted in play areas or near pools or sun terraces. The use of string trimmers and other power
tools should be avoided at midday and operatives should be clothed and wear gloves. Sunscreens,
which protect against UVA as well as UVB may help to protect plant handlers when protective
clothing and gloves are impracticable.47
FIGURE 6.13 Heracleum mantegazzianum naturalized on river banks at Charmouth, South Dorset.
FIGURE 6.15 Dictamnus albus, growing wild in the Pindus Mountains, Greece.
FIGURE 6.17 Phototoxic reaction after handling figs; the reaction spares the area protected by a ring (courtesy
of Dr. John Cook).
Jean-Pierre Lepoittevin
CONTENTS
7.1 Introduction
7.1.1 Testing with Plants
7.1.2 Identifying the Allergen
7.2 Preparation of Plant Extracts
7.2.1 Solid–Liquid Extraction
7.2.2 Liquid–Liquid Extraction
7.3 Isolation and Purification of the Allergen
7.3.1 Thin Layer Chromatography (TLC)
7.3.2 Liquid Chromatography (LC)
7.3.3 Gas Chromatography (GC)
7.3.4 High Performance Liquid Chromatography (HPLC)
7.4 Identification of the Chemical Structure of the Allergen
7.4.1 Mass Spectrometry (MS)
7.4.2 Spectroscopic Techniques
7.4.3 Infrared (IR)
7.4.4 Ultraviolet—Visible (UV)
7.4.5 Nuclear Magnetic Resonance (NMR)
7.4.6 Determination of the Structure
7.5 Conclusion
7.6 References
7.1 INTRODUCTION
Because of the multitude of substances they contain, plants are responsible for many types of
dermatosis or phytodermatosis.1 This study is rendered difficult by the very large number of plant
species, with more than 300,000 identified and classified at the present time. In addition, the plant’s
chemical composition can be highly variable and depends, to a great extent, on the site and climate.
Phytodermatoses are, therefore, often regional phenomena highly dependent on the patient’s occu-
pation. The very high geographic mobility of people and goods makes the problem even more
complex owing to the presence in our environment of plants or objects of plant origin originating
in the four quarters of the globe.
Following each stage of purification, the different fractions must be tested on the patient (or
on previously sensitized animals) in order to follow the biological activity through the purification
process. This especially cumbersome assay method is a further major hindrance to the identification
of plant allergens.
various substances can be detected directly (colored substances), under UV light (UV absorbing
materials) or by staining using specific or nonspecific chemical reagents. Each substance is char-
acterized by its frontal retention defined as:
This value is characteristic of a given product in a given solvent. Thin layer chromatography
is a highly sensitive method that can be applied to very small amount of material. It is, therefore,
of great analytical use for the qualitative analysis of a mixture of products or to check the purity
of a compound.
The main stationary phases used are silica, alumina, and cellulose. It is also possible to use
phases chemically modified for particular needs; for example, to analyze highly lipophilic products,
it is possible to use stationary phases of silica to which have been bonded to lipophilic 18 carbon
chains (reverse-phase C-18).
The chief mobile phases, in order of increasing polarity, are the hydrocarbons (hexane and
pentane), ethyl ether, ethyl acetate, and methanol.
stationary phase, but the solvent must be circulated at high pressure to compensate for the loss of
charge. This is currently the most powerful chromatographic method for separation and analysis.
A very large variety of stationary phases (direct or reverse) can be used and partition or ion-exchange
chromatography performed.
into a magnetic field, the ionized molecules deviate from their trajectory to an extent depending
on their mass/charge ratio. Knowing the charge of the molecule, it is then possible to calculate the
molecular weight with great precision.
Mass spectrometry also provides other information. During electronic bombardment, the trans-
ferred energy is usually sufficient to cause fragmentation of the molecules. Splitting does not occur
randomly and certain ions are preferentially formed. Analysis of the mass of these fragments yields
valuable information about the structure of the molecule.
The infrared radiation is absorbed and converted into rotational and vibrational energy. The
absorption frequencies depend on the relative masses of the atoms, the binding force constants, and
the geometry of the atoms. Each molecule, therefore, gives absorption bands characteristic of its
constituent bonds. The absorption bands are particularly strong and characteristic when they involve
atoms of different types and/or multiple bonds. It is, therefore, a very good method for detecting
the presence of single or multiple C–O bonds, such as alcohols, ketones, aldehydes, esters, amides,
or acids, and also C–N bonds (single or multiple) and certain multiple-bonded forms of carbon.
The chemical shift value makes it possible to obtain valuable information regarding the direct
environment of each atom studied.
When the magnetic moments tend to align themselves with the external magnetic field, they
produce between themselves interactions called spin–spin coupling. This effect is transmitted to
neighboring nuclei by the bonding electrons and results in signal multiplicity which depends on
the number of neighbors, with the distance between two bands depending on the dihedral angle
between the neighbors. This information, even if it complicates the reading of the spectrum, is very
important because it makes it possible to piece together how the different atoms are connected and
to have an idea of their respective orientations.
By means of certain NMR manipulations, it is also possible to demonstrate interactions across
the space between the atoms. This information makes it possible to build up the three-dimensional
structure of the molecule.
• Mass spectrometry gives the molecular weight and certain information regarding the
molecule fragments. It is, thus, possible to have access to certain known and identifiable
fragments.
7.5 CONCLUSION
The identification of a natural allergen is never a simple routine operation but requires the use of
sophisticated methods generally involving several months of work.
7.6 REFERENCES
1. Benezra, C., Ducombs, G., Sell, Y., and Foussereau, J., Plant Contact Dermatitis, Mosby, St. Louis,
1985.
2. Bloch, B. and Steiner-Wourlisch, A., Die willkürliche Erzeugung der Primel über Empfindlichkeit
beim Menschen und ihre Bedeutung für das Idiosynkrasieproblem, Arch. Derm. Syph. (Berlin), 152,
283, 1926.
3. Tomb, R., Patch testing with frullania during a 10-year period: hazards and complications, Contact
Derm., 26, 220, 1992.
4. Gäfvert, E. and Karlberg, A.-T. Isolation and identification of contact allergens, in Allergic Contact
Dermatitis: The Molecular Basis, Lepoittevin, J.-P., et al., Eds., Springer, Berlin, 1997, 43.
CONTENTS
8.3.2 CHEMICALS
Recommended screening batteries of photoallergenic chemicals are available. These differ from
country to country, and may be modified according to the patient’s history. When botanical pho-
toallergy is suspected, the patient should bring in all suspected plants with which there has been
contact. Portions of the plant, for example, the stem, leaf, root, and petal may be gently crushed
and applied under tape for photopatch testing. For some plants, the specific photoallergen may be
available commercially for patch testing. Irritant plants, for example, psoralens-containing plants
should not be photopatch tested because a photoirritant reaction can be predicted.
8.3.3 VEHICLES
Each chemical or portion of the plant to be tested should be incorporated into a suitable vehicle,
for example, petrolatum, in aluminum chambers.15 When a suspected case is negative with petro-
latum as the vehicle, consider alternative solvents such as ethanol.
8.3.4 CONCENTRATION
A concentration of 1 percent was previously thought to be ideal. However, photoallergenic com-
pounds are frequently phototoxic as well, therefore, in photopatch testing the potential allergen is
diluted to a level where phototoxic reactions are not seen.
8.3.5 TAPE
The sites must be quickly and rigorously covered with opaque material to prevent stray radiation.
Water-resistant tape, such as Scanpor, is frequently used.
8.7 CONCLUSION
Although photomaximization tests have shown that plants are potentially potent photosensitizers,
this does not translate well in practice—few well-documented cases of photosensitizing plants exist.
Insufficient controls and variations in photopatch testing procedures, materials, recording, and
interpretation of results hinder identification of true photosensitizers. Standardization of the pro-
cedure and, in particular, incorporating normal controls when appropriate, may lead to more plants
being identified as photosensitizers in the future.
CONTENTS
9.1 Introduction
9.2 Toxic Anacardiaceae (Anacardium)
9.2.1 Overview
9.2.2 Description
9.2.3 Clinical
9.2.4 Chemistry
9.3 Buchanania
9.3.1 Overview
9.3.2 Description
9.3.3 Clinical
9.4 Campnosperma
9.4.1 Description
9.4.2 Clinical
9.4.3 Chemistry
9.5 Comocladia
9.5.1 Overview
9.5.2 Description
9.5.3 Clinical
9.5.4 Chemistry
9.6 Drimycarpus
9.6.1 Overview
9.6.2 Description
9.6.3 Clinical
9.7 Gluta
9.7.1 Overview
9.7.2 Description
9.7.3 Clinical
9.7.4 Chemistry
9.8 Holigarna
9.8.1 Overview
9.8.2 Description
9.8.3 Clinical
9.9 Lithraea
9.9.1 Overview
9.9.2 Clinical
9.9.3 Chemistry
9.2.2 DESCRIPTION
The cashew is a small tree, sometimes shrub-like, with a trunk rarely exceeding 6 in. in diameter
and a height of 12–24 feet. It has a dense, irregular crown. The bark is light gray-brown, smooth
to lightly fissured. There is a whitish to reddish-brown inner bark that contains the milky latex.
The twigs are yellowish-green and fuzzy when newly formed. The simple, leathery, elliptic leaves
9.2.3 CLINICAL
Although the cashew plant contains phenols producing allergic contact dermatitis, their concentra-
tion in the nutshell is such that, if undiluted, they induce an immediate vesicant action.3,4 Indeed,
oil oozing from damaged nutshells has been used in Africa to produce ritual scarification and keloid
formation,5 and it has been employed medically for the removal of warts.6
Chronic irritant dermatoses of the palmar surface of the hand are produced in unprotected
agricultural workers.7 The fumes from roasting nuts during processing are very irritating. In a
processing plant in India, (ostensibly irritant) blackish crusting was noted in almost all of the
workers examined, but allergic reactions were much less common.8
Dock workers unloading unprocessed nuts have experienced contact dermatitis. Because the
phenols oxidize in air to produce a shiny black varnish, at one time vanilla beans were coated with
cashew nutshell oil to increase their attractiveness leading to the so-called vanilla bean dermatitis
in dock workers and food handlers.5 Workers in a cashew-nutshell oil processing plant may
experience allergic contact dermatitis, but after continuing to work they seem to develop hardening
so that they are less sensitive or even patch-test negative. Only 2 of 19 workers tested in one study
reacted,9 and persons allergic to poison ivy may see a diminution of the level of sensitivity.10
Eating cashew nut butter contaminated with cashew nutshell-oil caused acute contact dermatitis
involving the perianal area,11 and systemic contact dermatitis involving the flexures and buttocks
has been reported from eating cashew nuts.12 A pesto sauce containing cashew nuts contaminated
by cashew nutshell oil caused systemic contact dermatitis with flexural accentuation, usually 1 to
3 d after ingestion.13
An unusual source of cashew nut dermatitis in children was imported toys made with unroasted
nuts.14 Similarly, adults may be affected from native-crafted jewelry or from party favors, such as
novelty swizzle sticks.15 The recent interest in unprocessed foods in health food stores has resulted
in reports of generalized dermal eruptions in poison ivy sensitized patients who consume large
quantities of raw cashew nuts.16,17 Although most attention is given to dermatitis caused by the
nutshell liquid, the latex also is present in vesicant concentrations in the tree bark.3,5
9.2.4 CHEMISTRY
During World War II, cashew nutshell phenols were used to form resins with electrical insulating
properties for military equipment. Considerable effort was expended on studying the cause and
nature of the dermatitis because of the strategic importance of these resins. Keil and Dawson4
demonstrated cross sensitivity between the cashew and poison ivy. These investigators determined
the nature of the sensitizing phenols and conducted some of the earliest structure-activity rela-
tionship studies in contact dermatitis. They established the importance of the ring position of the
alkyl side chain, its degree of unsaturation, its chain length, and the necessity of the free phenolic
group. They also investigated the relative sensitizing potency of the various phenolic cashew
components.
9.3 BUCHANANIA
9.3.1 OVERVIEW
Buchanania is likely a benign genus because it is common, but reports of toxicity are not common.
Beaman, in 1986, examined the genus in Sabah and found no reactions and no black spots in the
plant press.20 The genus, named for the Scottish botanist, F. Buchanan-Hamilton (1762–1829),
includes about 25 species of trees. These are largely distributed in tropical Asia, Australia, and the
South Pacific.21
9.3.2 DESCRIPTION
The taxon has simple leaves and the bisexual 5-merous flowers, with 5 petals and 10 stamens. The
presence of four to six free carpels rather than the single carpel or compound pistil (as found in
all but one other genus of Anacardiaceae) is the most distinctive feature of the genus.
9.3.3 CLINICAL
There is a report by Altschul,22 of a herbarium specimen of Buchanania lucida Bi. (B. arborescens)
collected in Sabah by Leandro that was labeled juice itchy and was called rengas. This suggests
some question about the potential for toxicity and, therefore, a need for further study.
9.4 CAMPNOSPERMA
The name for Campnosperma comes from Greek and means bent seed. The genus comprises about
10 species of trees of tropical America, Madagascar, and Asia.21,23 An oil from some species of
Campnosperma has been used to prevent parasitosis.20 Timber of C. auriculatum is used for making
canoes, and the exudate from the wood is called terentang-oji. The genus seems to have no English
common name, but one of the more commonly applied vernacular names in Malaysia and Indonesia
is terentang. Campnmosperma has also been reported in Africa (Madagascar).24
9.4.1 DESCRIPTION
Campnosperma has simple leaves, mostly unisexual flowers, stamens twice the number of the
petals, a 1-loculed ovary, and only one stigma and style.20 Campnosperma aurnculaturn (B 1.)
Hook.f. can be found in coastal peat swamps, as well as on well-drained soils up to 1600 m
(5200 ft).20
9.4.2 CLINICAL
This genus is not often reported to be allergenic, but Ding Hou21 mentioned that C. auriculatum
induced “a bad attack of irritation similar to that of rengas,” and Corner25 and Burgess26 have also
implicated the sap in causing allergy in some persons.
9.5 COMOCLADIA
9.5.1 OVERVIEW
This genus essentially is confined to the Caribbean islands, although there are four species along
the southwestern coast of Mexico, one of which extends into Guatemala. None is present in the
United States or South America. There are perhaps 20 species in all, but the genus is in need of
taxonomic revision. A number of published species may represent immature forms or local variants.
Only one species will be described and only a few selected species will be discussed.
9.5.2 DESCRIPTION
Comocladia glabra is representative of this genus. It grows as a small tree to about 20 ft tall at
sea level. At higher elevations, it becomes more shrub-like, and it is vine-like on cliff faces. The
characteristic of this genus is that the leaflets of the pinnately compound leaves have spine-tipped
dentate margins. (This characteristic is particularly pronounced in C. dodonaea.) The plant contains
a whitish latex that turns black on exposure to air. The minute red flowers are borne on a panicle.
The fruit is a small drupe bearing a single seed.
9.5.3 CLINICAL
The latex turns black on exposure to air and a drop leaves a black spot on the skin28 (similar black
spots on the skin are a rare consequence of poison ivy exposure).29 An early and detailed description
of the course of Comociadia dermatitis is given by Pardo-Castello.30 Comocladia dentata (Figure
9.1), known to the populace on Grand Cayman as maiden plum, is avoided by the local population
because of its reputation as a toxic plant.
9.5.4 CHEMISTRY
The chemistry of the sensitizing phenols from this genus has not been explored. Their concentration
in the latex is sufficiently great that it has been used in medicine for the removal of warts and
corns.28,31
9.6 DRIMYCARPUS
9.6.1 OVERVIEW
Drimycarpus (from Greek, pungent fruit) is an unfamiliar genus of trees of southern Asia. It was
long considered to have only a single species, Drimycarpus racemosus (Roxb.) Hook.f. ex March.,
but a second species was added by Ding Hou in 1978 by the transfer of Drimycarpus luridus
Hook.!. Ding Hou, formerly included in both Semecarpus and Swintonia.
9.6.2 DESCRIPTION
Leaves of Drimycarpus are simple, with a distinct marginal nerve.20 Flowers are mostly unisexual
and are especially distinctive and have an inferior ovary (which is quite distinctive). There is a
single style with three stigmas. In the field, these plants look very much like Mangifera, Mel-
anochyla, and Semecarpus.21
9.6.3 CLINICAL
Beaman states that he had “seen no explicit statement about allergenic properties of Drirnycarpus;
however, as a member of the tribe Semecarpeae, it must be suspected”20 as all of the other three
genera in the tribe are allergenic, especially Semecarpus. In addition, the common names are also
somewhat incriminating.
9.7 GLUTA
9.7.1 OVERVIEW
The name Gluta comes from the Latin word for glue. This genus comprises about 30 species of
trees or sometimes large shrubs found throughout most of Southeast Asia. The capacity of this
genus to cause dermatitis is well established.
9.7.2 DESCRIPTION
Ding Hou21 combined the genus Melanorrhoea, a name much used in the literature on Southeast
Asian Anacardiaceae, with Gluta, because the known variations between the taxons does not allow
clear separation. Gluta has simple leaves and bisexual flowers. It also has a calyptriform calyx and,
frequently, numerous stamens, absence of a disk, and a single stigma and style. There is considerable
variation in flower structure, however, which makes it difficult to make sharp distinctions of the
genus. Some species of Gluta are found in peat swamps and along rivers where they may be a
dominant vegetation. Individual trees also are found widely throughout much of the lowland tropical
forest in Borneo.
9.7.3 CLINICAL
Beaman20 describes a collection of Gluta wallichii (Hook.!.) Ding Hou in lowland primary forest
of the Malaysian state of Sabah. His party used a rope thrown over a limb to secure fruiting material,
and all four in the party developed a severe dermatitis despite attempted precautions. He also woke
up one morning on an expedition there to find black sap on the bunk where he had slept. His guides
had made a bed with poles of rengas for use as a bed on the rocky terrain. This was probably a
species of Gluta. The resultant dermatitis appeared within 15–20 h of contact and the sleeping bags
have black spots from these poles to this day.20 He describes a worker who had used a chain saw
to cut down a tree and had developed severe contact dermatitis over most of his upper body, probably
also from Gluta. A similar example was given by Gimlette.34
Dermatitis may be seen in Southeast Asia from gathering firewood as well as producing and
wearing lacquerware.32
Beaman20 also describes a vindictive poison made by mixing sap of Gluta with setae of the
bristleworm and crystals from the decayed fruit of Raphidophora giganteum (Araceae). This poison
is administered by smearing it on the clothes or sleeping mat of the victim.34 Where Gluta occurs,
it is commonly called rengas (or renghas), but many other vernacular names are also used, especially
jitong.34 According to Burgess,26 the name rengas is used for many trees in the Anacardiaceae that
have a black sap, sometimes wrongly. However, the black varnish is an excellent screen to use for
the allergenic species.35
This genus has also been known to be transmitted to persons wading in water as discussed in
Upwich and cited by Senear.36
9.7.4 CHEMISTRY
The fruit sap of Gluta renghas L. reportedly contains the monoethenoid alkyl catechol, glutareng-
hol.37 G. usitata contains thitsol, 4-heptadec(en)ylcatechol (MW 344).32
9.8 HOLIGARNA
9.8.1 OVERVIEW
Holigarna (from hulgeri, a local Deccan name) comprises approximately eight species of trees,
found in India, Thailand, and Vietnam, but the range does not extend as far as Malaysia.38-40
9.8.2 DESCRIPTION
Holigarna has simple, evergreen leaves that are distinctive because the petiole has 1–2 pairs of
deciduous spur-like appendages. The flowers are unisexual, with valvate petals, inferior ovary, and
three styles and stigmas.20
9.8.3 CLINICAL
Holigarna arnottiana Hook. f. ostensibly contains an acrid black juice7 in quantity that appears at
sites of plant injury. Because not all exposed break out, it is thought to be an allergic reaction.37,38
Both the fruit and the bark are said to have been used (with caution) medicinally.20
9.9.2 CLINICAL
The genus was first reported to be medically important in 1877, when a facial dermatitis was caused
by introduction of litre leaves into the oral cavity to alleviate toothache.41 In experimental exposure
of 10 volunteers who rubbed leaves of the plant on their arms, only 5 developed reactions on the
rubbed site. One was accompanied by an enormous swelling of the face.42 The resultant skin lesions
reportedly are delayed, are usually vesicular or bullous, and are often accompanied by swelling of
the skin of exposed sites.42
9.9.3 CHEMISTRY
The chemistry of Lithraea is said to be somewhat similar to poison ivy comprising 3-penta and 3-
heptadec(en)ylcatechols.44 Guinea pigs sensitized to L. molleoides were also reactive to T. radi-
cans,45 and persons known to be allergic to litre are also sensitive to poison oak urushiol,44 and T.
striatum46 on patch testing.
9.9.5 CLINICAL
The first medical report on litre dates from 1877. It states that facial dermatitis was caused by the
introduction of litre leaves into the oral cavity to alleviate toothache. Reyes42 experimented with
10 volunteers who agreed to rub litre leaves on their arms. Only five had delayed skin reactions
9.10 LOXOPTERIGIUM
9.10.1 OVERVIEW
Loxopterigium sogotii is popularly called picatón, meaning that it itches and suggesting that it has
allergenic properties. There are a few voucher specimens of L. sagotii Hook., collected in eastern
Venezuela, available at the National Herbarium in Caracas. L. sagotii also has been found in British
Guiana150 and Suriname.51 L. lorentzii has the common name of mal de quebracho.37
9.10.2 CLINICAL
The juices of picatón have been called an irritant to the skin.52
9.11 MANGIFERA
9.11.1 OVERVIEW
North Americans often tend to think of Mangifera (from the vernacular, mango, and Latin, to bear)
as including a single species, Mangifera indica L. (mango). However, Mangifera is a large genus
of trees comprising about 35 species widely distributed throughout Southeast Asia. It is perhaps
most diverse in the region of the Malay Peninsula, Sumatra, and Borneo. The mango has been
cultivated in India for over 4000 years and is said to have over 1000 cultivars.20
The mango, a native of Asia, has become a popular fruit tree in tropical America. It was
introduced into the West Indies in 1742, but it was brought into Mexico and Brazil in the late
seventeenth century.2 It is also cultivated in southern Florida and, on a smaller scale, in Texas and
southern California. However, mango is planted everywhere in both Central America and the
Caribbean, and it has, naturally, escaped from cultivation. This plant is somewhat cold-sensitive,
so it tends not to thrive at altitudes greater than 4000 ft.2 Although the trees are not generally
common, Mangifera is sometimes used for lumber, going under the Malay common name
machang.20 Mango fruit can be eaten raw or dried and made into jams, jellies, pickles, and
chutneys.21
9.11.3 CLINICAL
Mango is not thought of as being toxic because it is eaten in much of the world. However, allergy
to this plant is well known.53-56 However, reports of reactions to this plant are less common from
tropical regions where consumption is commonplace. This has prompted some to postulate that
consumption of mango early in infancy and thereafter may cause a form of tolerance. The sensitizing
principle is contained in lactiferous ducts within the stem attached to the fruit.2 Patch tests are
positive to sap, leaf, stem, and fruit skin.57 If the fruit is picked, about 1 ml of latex may spill onto
the skin of the fruit. This oxidizes to a shiny varnish. However, the fruit, when peeled, may be
eaten safely by persons who might otherwise be allergic. When the fruit is eaten whole without
removal of the skin, the most common pattern, a circumoral dermatitis and cheilitis, may also be
seen. Stomatitis is less common.2,55 Some agricultural workers develop a more widespread hand-
transfer dermatitis of the face, neck, and genitals.2 Persons allergic to poison ivy or poison oak
tend to be cross sensitive to the mango.2
Mango dermatitis may be less common in those who grew up eating mango. In a study in
Hawaii, the natives of the Islands comprised only 12 percent of the patient population with mango
dermatitis, but they represented 72.5 percent of those with phytophotodermatitis.58 This has been
attributed to their first exposure being oral rather than cutaneous.58
Burgess26 included sap from the bark, smoke from bonfires of Mangifera leaves, and raindrops
from tree crowns among sources of exposure. He notes that timber cutters are reluctant to cut the
trees because of their irritant sap.
While most reactions to this genus are to Mangifera indica, other members of the genus
reportedly can also cause dermatitis. These include M. lagenifera, M. caesia, M. foetida, M.
kemanga, and M. odorata.37
9.11.4 CHEMISTRY
The major component of mango latex is 5-2(Z)-heptadec(en)yl] resorcinol.59 The toxic principle is
mainly in the fruit rind, but it can also be found in other parts of the tree. Allergenic species include
Mangifera caesia Jack, M. foetida Lour., M. lagenifera Griff., and M. odorata Griff.20
9.12 MAURIA
9.12.1 OVERVIEW
Hurtado et al.60 reported the toxic properties of Mauria puberula in 1982, but according to Lampe,2
M. puberula may be only a variant of M. heterophylla. There are, perhaps, 10–20 species in the
genus Mauria, mostly in Venezuela and Peru. According to Blackwell and Dodson61 Mauria glauca
J.D. Sm. and M. birnngo Tulasne are synonymous with M. heterophylla H.B.K., so this may be
9.12.2 DESCRIPTION
Mauria heterophylla is a small tree some 12–25 ft high, located in the humid upland forests of
Central America, Peru, and Colombia.2,41 Its pinnately compound leaves have 5–7 leaflets. The
white or yellow flowers and the fruit (a drupe) are small and borne in panicles. Hurtado equates
this taxon to M. simplicifolia, and separates it from M. puberula saying that it is a less well-known
species found not only in Venezuela but extending into Colombia and Peru and it is also toxic.41
9.12.3 CLINICAL
Dermatologic reactions to only a few of the South American species, have been described in the
medical literature.60 Mauria puberula is quite similar to M. heterophylla and may be only a variety.2
The only references to such a response for M. heterophylla are in a botanic monograph and on
herbarium sheets, the first of which (as M. glauca) states, “poisonous to some persons, producing
dermatitis and fever.”64 The herbarium annotations read (as M. biringo in Panama), “ ‘Siguella’ is
claimed to be poisonous by the natives;” (as M. heterophylla in Peru) “Produces skin eruptions in
some persons.”22
M. jaramubi, a new Colombian species, called tatacoa (a name meaning poisonous animal) is
also toxic, causing lesions similar to those produced by exposure to T. striatum.41
9.12.4 CHEMISTRY
No chemical studies have been conducted on this genus; however, it was shown that the South
American species, M. puberula, produces dermatitis in 3-pentadecylcatechol-sensitized guinea pigs
and in patients previously sensitized to other genera of Anacardiaceae.41,60
9.13 MELANOCHYLA
9.13.1 OVERVIEW
Melanochyla (from Greek, black sap) is a somewhat unfamiliar genus comprising 17 species of
trees in the Malay Peninsula, Borneo, Sumatra, and Java. Trees of this genus are found almost
exclusively at low levels of primary forests in either swamps or uplands.
9.13.2 DESCRIPTION
This genus has simple leaves, usually papillose beneath. Flowers are mostly unisexual, with the
petals villous or woolly inside. The filaments also are villous. The ovary is deeply set in the
hypanthium, 1-loculed, with a single style and three stigmas.21
9.13.3 CLINICAL
Most species are commonly called rengas, probably because the natives do not distinguish Mel-
anochyla from Gluta and Semecarpus. The economic value of Melanochyla is little mentioned
except for its use as timber. However, it is not usually cut for timber because of the irritant sap.26
9.14 METOPIUM
9.14.1 OVERVIEW
There are three species of Metopium found from subtropical Florida, through the Caribbean, to the
Netherlands Antilles, and to the mainland of Central America including southern Mexico, Belize,
and Guatemala. Metopium toxiferum, which is the only species of Metopium found in the continental
United States, grows in the southern tip of Florida. Where it is protected from fire, it may reach
40 ft in height.
9.14.2 DESCRIPTION
All three species are trees, differing in leaflet shape and in the structure of the flower and bud. The
odd-pinnate compound leaves may have three to seven leaflets, but usually have five. Leaflets are
3–4 in. long, leathery, and somewhat shiny on the upper surface. With time, the leaf tends to develop
black spots at the sites of mechanical or insect injury. Natives often recognize the tree from its
thin, reddish bark, that flakes to exude a clear, sticky resin that blackens with exposure. The long-
stalked panicles of flowers, seen only on new growth have five minute, yellowish-green petals and
are relatively inconspicuous. The fruit, tan or orange at maturity, is a small drupe, about 1/2 in.
long, containing a single seed.2
9.14.3 CLINICAL
Each of the species is associated with dermatitis65-67 from the sensitizing catechols in exterior parts
of the tree. The wood68 and pollen69 are not toxic.
9.14.4 CHEMISTRY
Chemical analysis of Metopium toxiferum shows mostly C-15 catechols similar to that of poison
ivy. The content is about equally divided between the C-8 monoene and the C-11 diene with a
small quantity of saturated 3-pentadecylcatechol. There are perhaps 5 percent with unsaturated
heptadec(en)yl sidechains and a trace (less than 0.2 percent) with nonyl substituted catechols.70
The sensitizing catechols70 are similar to those of poison ivy, but this plant is quite toxic in all
exterior parts of the tree, producing strong black spots on specimens collected and causing dermatitis
in persons who normally do not react to poison ivy.
9.15 NOTHOPEGIA
9.15.1 OVERVIEW
Nothopegia (from Greek, a false Pegia, another genus of Anacardiaceae) is a genus comprising
about six species of shrubs and trees found in India and Ceylon. The plants occur in semi-evergreen
or deciduous forests.40 They are not on record to be economically important. A common name in
Sri Lanka (Ceylon) is bala.23
9.15.2 DESCRIPTION
Leaves are simple and flowers are usually unisexual (but sometimes bisexual) and are 4-merous,
with a single style and a barely 3-lobed stigma.20
9.16 PARISHIA
9.16.1 OVERVIEW
Parishia (for C. S. P. Parish, 1822–1897, an English botanist) comprises five species of deciduous
trees that are distributed from Burma and Thailand to the Malay Peninsula, Borneo, and the
Philippines.
9.16.2 DESCRIPTION
Leaves are pinnately compound and deciduous. The flowers are 4-merous, unisexual, and the 4-
lobed calyx is much enlarged in fruit, forming wings. The ovary is 1-loculed, the style 3-parted,
and the drupe densely pubescent.
9.16.3 CLINICAL
Mitchell and Rook37 attribute a report of dermatitis from Parishia wood to Senear,36 but Beaman
could find no mention of the genus in that paper.20 It is possible that there was confusion of Parishia
maingayi Hook. f. with Melanorrhoea maingayi Hook. f. (equivalent to Gluta wallichii) that was
mentioned by Senear. Burgess26 considered the sap to be nonpoisonous. Although the common name
rengas susu has been applied to P. maingayi, many common names have been used for this and the
other species.21,26 It seems that the allergenic properties of Parishia remain to be demonstrated.
9.17 PENTASPADON
9.17.1 OVERVIEW
Pentaspadon comes from the Greek, five and eunuch, to indicate the five sterile stamens. The genus
comprises six species of large deciduous trees found in the region of Thailand and Vietnam to the
Malay Peninsula, Sumatra, Borneo, the Moluccas, New Guinea, and the Solomon Islands. A black
resin from the tree has been used to treat parasitic itches, but the severity of the skin irritation of
the skin limits that.20
9.17.2 DESCRIPTION
Leaves are compound, and flowers are bisexual, 5-merous, and usually with 5 stami nodes in
addition to the 5 stamens. There is a single style and stigma (which is sometimes slightly 2-lobed),
and a 1-loculed ovary.
9.18 PSEUDOSMODINGIUM
9.18.1 OVERVIEW
Pseudosmodingium comprises five species, but some are not well defined.71-73 All are restricted to
Mexico. The gummy exudate from the trunk is said to be acrid37 and to have a carrion odor.2
9.18.3 CLINICAL
These plants produce a poison ivy-like dermatitis.71-73
9.18.4 CHEMISTRY
The chemistry of the plant is not well-known.
9.19 RHUS
9.19.1 OVERVIEW
We have previously stated many reasons that Rhus is separate from Toxicodendron. Mitchell and
Rook37 list several species of Rhus as causing dermatitis, but the problem may be one of nomen-
clature because several of the taxons mentioned are known to be misclassified as Rhus in those
reports. For example, Rhus juglandifolia and R. striata are Toxicodendron striata, R. metopium is
Metopium toxiferum, and R. punjabensis was mistaken for Toxicodendron wallichii.74 There is one
report of R. typhina, staghorn sumac, possibly causing dermatitis. If this plant ever causes a problem,
we have never seen it. The plant produces a negative black spot test, and no specimen of Rhus that
we have collected has caused black spots on the paper. Therefore, any allergic reaction would have
to be to a component other than a substituted catechol or resorcinol. In short, true Rhus is a benign
genus.
9.20 SCHINUS
9.20.1 OVERVIEW
Schinus comprises some 28 species, mostly indigenous to South America, with some that range
into Mexico. Perhaps the best known for its problems is the Brazilian pepper-tree, Schinus
terebinthifolius, which since it was introduced into Florida, has become something of a pest. In
Florida, it is known as Florida holly where it has escaped cultivation and become a part of the
flora. The worst part is that it has seemingly resisted all efforts at eradication. The plant is said to
be controlled where the land reverts to swampland, but the economics of the area do not allow
that methodology.
9.20.2 DESCRIPTION
Schinus terebinthifolius is a small tree reaching some 25–30 ft.2 Leaves are compound odd pinnate
with five, seven, or nine leaflets often toothed and attached directly to a winged rachis. The injured
specimen when collected has a peppery-turpentine odor.2
9.20.3 CLINICAL
Dermatologists in Florida generally consider this plant to cross-react with poison ivy,75 although
this remains to be proven. The latex from bark and crushed berries is said to cause allergic contact
dermatitis,6 and has been called the most common cause of allergic contact dermatitis in South
Florida.75 It was also the cause of the pink peppercorn caper, when its use as a seasoning was
followed by outbreaks of diarrhea and perianal dermatitis.
9.20.4 CHEMISTRY
Schinus terebinthifolius contains a number of terpenes, but the sensitizing fraction is said to be a
3-pentadec-8-enyl phenol,203 also known as cardanol and present in cashew. Unfortunately, the
chemical study cited used only the fruit and other chemists who have attempted isolation of the
toxic fraction have found inconsistent data. Dr. Jerry McLaughlin at Purdue University isolated a
nonadecyl phenolic from one specimen from the Florida Keys (collected by George Avery) and
could not duplicate this with subsequent collections (also collected by Avery) later the same year.
Brian Lawrence also told one of us (Guin) that he had also experienced problems in consistently
isolating a toxic principle from this plant.
9.21 SEMECARPUS
9.21.1 OVERVIEW
Semecarpus comprises many species, all of which are probably allergenic.20 One is illustrated in
Figure 9.2. The best known example is Dhobi-mark dermatitis as reported by Livingood and
FitzHugh (see below). Many of these species are found in a limited geographic area and to this
day all species may not be well known. The name for the genus, Semecarpus, comes from Greek,
referring to the juice of the fruit used for marking cloth. The taxon includes some 60 species ranging
from India to Ceylon, Burma, Thailand, Indochina, Taiwan, Australia, Micronesia, the Solomon
Islands, New Caledonia, and Fiji.20
9.21.2 DESCRIPTION
The individual species may be trees, treelets, or shrubs. The genus has simple leaves that are often
papillose on the lower surface. The leaves vary greatly in size, as may be seen in Semecarpus
borneensis Merr. with relatively small leaves, and the Semecarpus sp. shown in Figure 9.2 with
very large leaves. The latter plants are treelets with a rosette of leaves near the summit of a slender
9.21.3 CLINICAL
Semecarpus anacardium, the Indian marking-nut tree, is also called Dhobi’s nut. The bhilawa oil
from the ripe pericarp is used in a mixture with lime water or lum25 or the green nut76 as an ink
to mark laundry. S. orientale also induced dermatitis in a laboratory worker cutting the fruit.77
Mitchell and Rook37 give numerous examples of contact dermatitis caused by clothing marked with
this substance, and they provide a list of other species of Semecarpus that cause contact dermatitis.
Apparently, there are two patterns in those using the nut for a laundry mark and two other patterns
in those wearing the marked clothing.
The persons making the laundry marking ink typically break out on the hands or face but may
break out on the legs if the nut is crushed in a mortar and pestle held between the knees.37 A
different pattern is seen in those wearing clothing marked with the plant extract. In 1943, Livingood
and FitzHugh evaluated an epidemic of contact dermatitis in military personnel of the 20th General
Hospital in the China Burma India Theater. Of the population exposed, 11 of 55 officers and 41
of 344 (enlisted) men developed contact dermatitis. The eruption was seen directly under the marked
spot on the individual’s clothing and in some of the more sensitive, eczema was found elsewhere.
The eruption responded promptly after contaminated clothing was avoided with the worst cases
sometimes taking two weeks. Re-exposure caused a return of the eruption. Some of the natives
believed that the rash occurred only in some because the tree had a like or dislike for certain
individuals.
Livingood and FitzHugh’s description76 of the marking procedure is somewhat different from
that of Mitchell and Rook. They saw the natives stick the (green) nut with a pin that was then
contaminated with a dark fluid that could be used to mark clothing. Patch tests to the ripe nut were
negative in 8 of 41 allergic subjects, but all of the 8 reacted to an extract of the green nut that was
said to have stronger allergenic properties.76 The marks were indelible, not removed by washing,
boiling, solvents, or sun exposure. Livingood and FitzHugh felt that there was some evidence that
repeated washing tended to diminish the allergic effect, but they recommended that the marks be
removed (excised) from the clothing of those affected.
Despite the numerous species of Semecarpus, relatively few commercial uses are recorded for
the genus, perhaps because it is such a potent contact allergen. The hypocarp of S. anacardium is
edible after roasting,25 and that of S. cassuvium is also said to be edible.21 The very young, white
(before chlorophyll is formed) leaves are said to be eaten raw,21 and the sap of this species is also
used as a black dye. The juice of the fruit wall is sometimes used as a treatment for ringworm and
has been called a cure for a rather heroic nature.78
9.21.4 CHEMISTRY
The allergenic chemical of Semecarpus anacardium L.f., called bhilawanol by some authors, is
reported by Loev79 as a mixture of cis and trans isomers of urushenol. Mitchell and Rook say that
S. heterophylla contains renghol, a pentadec(en)yl catechol with one unsaturated bond in the side
chain. It is unlikely that examination of multiple clones will reveal only one chemical because this
would be unusual for the more modern studies of the various Anacardiaceae. S. australiensis
contains a principle similar to poison ivy.80 Mitchell and Rook list S. vernicifera (used to make
Formosa lacquer) and S. travancorica among species containing Laccol, a catechol with a dienoic
3-heptadec(en)yl substitution.
9.22.2 DESCRIPTION
The plant can be seen growing as a shrub, a tree up to 20 ft tall or as a climbing vine.81 The leaves
are trifoliate81 or ternate. The plant, similar to many of the Anacardiaceae, may demonstrate brilliant
autumnal colors for which it has been planted.
9.22.3 CLINICAL
The clinical dermatitis is caused by contact with sap from the injured plant, much like poison ivy,
and the presentation of the rash is similar. Contact may occur in private gardens or less typically
in public parks and playgrounds.81 This species cross reacts in much the same way as (western)
poison oak, which it mimics in its chemistry.81
9.22.4 CHEMISTRY
The toxic material, which tends to contain heptadec(en)yl catechols as mono- or diolefins, is carried
in resin canals,84 similar to T. radicans.
9.23 SPONDIAS
9.23.1 OVERVIEW
Spondias (Greek name for plum) comprises 10 species found in the Indo-Malesian and American
tropics.21 Three species of Spondias are Malesian, while two others are American. Spondias mombin
L. and S. purpurea L. are cultivated widely in the Asiatic tropics. S. mombin is cultivated as a shade
tree, but its fruits are inedible. S. purpurea, however, is grown for the fruit (which is said to taste
like plums in turpentine).25
9.23.2 DESCRIPTION
The pinnate compound leaves have leaflets with a distinct vein running near the margin. The four
or five petals are valvate. Usually there are 10 stamens. The ovary can be from 5- to 1-loculed,
and there are from one to five styles.
9.23.3 CLINICAL
Spondias is generally considered an unlikely source of dermatologic problems.20 However, Mitchell
and Rook37 quote Woods and Calnan who had a sawyer with contact dermatitis and a strong positive
patch test to the sawdust of S. mombin. The bark of S. pinnata has been said to be an irritant.38
9.24.2 DESCRIPTION
The simple leaves have a marginal nerve, and the lower leaf surface of some species is distinctly papillate.
A distinctive feature of the genus is that the five petals are persistent and become much enlarged with
fruit. Beaman20 describes their functioning like helicopter blades to disperse the fruit, a situation similar
to that in some species of Gluta. The ovary is 1-loculed and there is a single style and stigma.
9.24.3 CLINICAL
Although Burgess26 considered the sap of the genus to be nonpoisonous, members of the genus have
black sap and their common name is rengas, suggesting that they may possess allergenic properties.
Foxworthy85 listed Swintonia along with Gluta, Holigarna, Melanorrhea, and Semecarpus as
the principle poisonous woods of Indo-Malaysia. Beaman points out, however, that some species
that were formerly included in Swintonia have been transferred to Gluta, however, so the status of
Swintonia as an allergen remains uncertain.
9.25.1 DESCRIPTION
Members of this taxon are shrubs to large trees with evergreen leaves. Leaves are alternate, pinnately
compound usually petiolulate, with approximately 5–9 leaflets, and secondary veins are joined
together in a series of marginal loops. The inflorescence is axillary or terminal, paniculate. Flowers
are pedicellate or sessile, cream colored to yellow or greenish yellow, 5-merous, petals imbricate,
usually with 10 stamens inserted below the intrastaminal disk; ovary densely pubescent, 1–3 locular.
The fruit is a fleshy drupe, reddish purple or black, and edible when ripe, stone without an
operculum. In tropical America seven or eight species are distributed from Mexico southward
through Central America and northern South America to Bolivia and Paraguay.88
9.25.2 CLINICAL
Exudate from this species is said on botanical records to be caustic and to cause dermatitis,41 and
freshly crushed leaves have been used as a vesicant.89 Dr. Tom Wendt, who has collected the
Mexican taxons, climbed them and eaten the fruit without ill effect. However, some of the local
people have complained of some burning of the mouth (personal communication from Tom Wendt,
Ph.D., Curator of Herbarium, University of Texas, Austin, TX).
9.26 TOXICODENDRON
9.26.1 OVERVIEW
Although the genus Toxicodendron is not considered by all taxonomists to be distinct from Rhus, the
evidence reviewed by Gillis74 strongly supports separation of these genera. Toxicodendron includes
about 30 species widely distributed in Asia and America in temperate areas and tropical mountains.
9.26.2 DESCRIPTION
Toxicodendron is a genus of small trees, shrubs, and vines with compound leaves except for T.
borneense (Stapf) Gillis with simple leaves. The flowers are unisexual and 5-merous, with five
sepals (or calyx lobes), five petals, and five stamens. The ovary is 1-loculed with a short style and
three stigmas. Toxicodendron has 15 species in China,90 and probably 8 species in the Malay
Archipelago. Only T. succedanea (L.) Moldenke (Figure 9.3) occurs in both areas. There are only
six species in the western hemisphere, so the diversity of poison ivy relatives is considerably greater
in the Old World. The chemistry of the allergenic compounds in Toxicodendron varies with the
taxon and is covered under the specific species.
Leaves of Toxicodendron species that have three leaflets per leaf are said to be ternate, while
those with more than three leaflets are odd pinnate. Toxicodendrons usually do not develop flowers
and fruit for three or more years, and until they do, one cannot separate male from female plants.
Flowering and fruiting structures arise between the leaf and the twig, so they are said to arise in
the axillary position (Figure 9.4). The petiole, which supports the three leaflets, is enlarged toward
its origin (Figures 9.4 and 9.5), and there is a groove on the distal surface through which the
flowering and fruiting structures arise (Figure 9.5). In North America, this feature can be observed
even during winter months when no leaves are present because the leaf scar left at the season’s
end is U- or V-shaped (Figure 9.5). The (terminal) flowering and fruiting structures of Rhus arise
at the end of the branch. Both Rhus and Toxicodendron are dioecious, that is, there are both male
and female plants. The male flowers (Figure 9.6) tend to have prominent stamens and are more
fragrant than female flowers (Figure 9.7). This often attracts bees and other insects during the
flowering season.
Individual fruits (Figure 9.4) are drupes. These are borne in panicles (Figures 9.4 to 9.7). The
female flowers when pollinated develop into fruits that are green during the growing season
(Figure 9.4) and become off-white in the fall of the year. The off-white exocarp often peels away
during winter exposing a chalk-white mesocarp with black lines (Figure 9.5) representing toxic
oleoresin within secretory canals within the mesocarp. The lines are oriented like longitudinal
divisions on a globe (Figure 9.5). The fruits found on mature female plants are helpful in winter
recognition, often allowing identification of small specimens of T. rydbergii that protrude above
the snow. Fruit, when heavy, tends to be pendant. This is especially true of T. diversilobum.
Another distinguishing feature is the tendency for Rhus to have hairs on the surface that are
glandular. Toxicodendron may or may not have hair (tricomes) on the surface, but in either case
the tricomes present do not contain glands. The tricomes in Rhus tend to be glandular. Pollen grains
of Toxicodendron are smaller, usually less than 32 mm in length. Toxicodendron also demonstrates
brown root hairs.
The sap of Toxicodendron tends to darken in the air, and one may see black spots that resemble
black enamel paint in areas of previous injury. This can often be helpful in field recognition. In
Malaysia and the Caribbean where even more toxic plants are found, the black stains on the trunk
of trees is often used to identify rengas and poisonwood (Metopium). Self-melanization of alk(en)yl
catechols is also the basis for the black-spots test, used to confirm the identification of toxic
Anacardiaceae in the field.
FIGURE 9.7 Female flowers of T. radicans ssp. negundo. (From Clinics in Dermatology, 1986, with
permission.)
a nonclimbing small shrub found from southwestern Texas to the northern tier of the United States
and Canada north of the 44th parallel and west of the region that has 29 or more inches of annual
rainfall.74
Western poison oak, T. diversilobum (Figure 9.9), unlike its eastern counterpart, grows in many
types of soils provided water is present in adequate quantity. The fruit on female plants is the largest
of the domestic toxicodendrons, and because of its weight, tends to be pendant. T. diversilobum,
or western poison oak, can be found from Baja California in Mexico to the lower latitudes of British
Colombia (Figures 9.10 a, b). It is mostly contained by the Rocky Mountains, but some local
dermatologists have found it in the mountainous regions of Nevada. This species, which is much
larger than eastern poison oak, has one of the widest ranges and the most varied soil type of any
California shrub.74 This species is commonly seen as a shrub, but it may develop aerial rootlets and
climb. Hair may be seen on the fruit as well as the bark of the branch.74,91
The fruit, a drupe that is largest among domestic toxicodendrons74 (up to 7.5 mm), is pendant74,91
and similar to ripe cherries. Lobes on leaflets are rounded but seem to be less stiff than those of
T. toxicarium. The shape of the leaflets, like T. toxicarium, has been likened to leaves of white oak,
but it is perhaps closer to those of live oak (Quercus agrifolia).92
T. toxicarium (Figure 9.11), eastern poison oak, is a small shrub found in sandy soil of poor
nutritional and low calcium content and, in the ridge and valley areas over sandstone outcroppings.
The range is shown in Figure 9.12. It tends to grow slowly so that plants less than 1 ft tall can
sometimes be seen producing flowers and fruit. Eastern poison oak, unlike T. radicans and T.
diversilobum (western poison oak), does not produce aerial rootlets and does not climb trees. It is
commonly seen in a savannah woodland (less than 50 years old) together with scrub oak trees such
as turkey oak, and pine, sassafras and bunch grasses. Gillis considered the habitat to be so distinctive
that it could be recognized from a moving automobile. Poison ivy and poison oak prefer different
soils, but in the southeastern United States they are still sometimes found rather close to each other.
They do not tend to hybridize because they do not flower at the same time, but this can be done
artificially and putative hybrids are occasionally seen in the field.
In locations where poison ivy [T. radicans ssp. radicans (Figures 9.13 to 9.15)] and poison
oak [T. toxicarium (Figures 9.11 and 9.12)] are both found, there are several characteristics that
can be used to distinguish them. Poison oak has hair (pubescence) on the leaves, petioles and fruit,
while T. radicans ssp. radicans tends to have tufts of hair in leaf axils (Figure 9.15). T. radicans
ssp. radicans tends to form aerial rootlets, while T. toxicarium does not. The morphology of leaflets
tends to depend somewhat on the maturity of the plant.
The archetype leaflets of poison oak resemble those of white oak (Quercus alba) so closely
that an experienced botanist has to be careful to look before grasping what seems to be a white
oak sapling in the woods, but leaf morphology of T. toxicarium is so variable that it is often
unreliable as a recognition feature.93 Lobes on leaflets are rounded, but leaflet morphology of eastern
poison oak is greatly variable with some clones essentially unlobed and many intermediate grada-
tions.93 The leaves on T. toxicarium arise fairly close together from the stem of the plant so the
foliage is said to be pseudoverticillate.
Plant chemistry is also somewhat different. The toxic principle in poison ivy comprises mostly
pentadec(en)yl catechols, while the oleoresin of poison oak contains mostly heptadec(en)yl catechols.
Toxicodendron radicans ssp. negundo (Figure 9.16), the dominant taxon of poison ivy in the
midwestern United States, is so named because its leaves can greatly resemble those of boxelder
(Acer negundo).74,91,97 Leaflets and fruit lack pubescence except some along veins on the leaflet
undersurface, but petioles show this.74 The lateral leaflets often have single lobes laterally that
resemble the thumbs of mittens with the palms upward.94,97 The range of this taxon (Figure 9.17)
overlaps many other U.S. subspecies (exceptions are T. radicans ssp. eximium and divaricatum),74,98
and hybridization is likely where there is geographic overlap.74
Toxicodendron radicans ssp. pubens (Figure 9.18), a plant of the fertile soil of the Delta region of
the Mississippi River and its tributaries, has glabrous fruit but broad, densely pubescent leaflets
with a dentate margin and prominent veins.74,91 The terminal leaflet is quite wide, often wider than
it is long. The foliage has a dull appearance caused by the dense pubescence.91 While the subspecies
archetype is found near the Mississippi River (Figure 9.19), this subspecies tends to contribute its
characteristics to putative hybrids in overlap areas.
Toxicodendron radicans ssp. verrucosum (Figure 9.20) grows in the limey soil74,91 southward from
the Arbuckle Mountains of Oklahoma along the Edwards Plateau of Oklahoma and Texas
(Figure 9.21).74 While some have confused this plant with poison oak because of the deeply lobed
leaflets, it is very different. T. radicans ssp. verrucosurn does not have pubescence on fruit and
leaflets. It is found in high-calcium (as opposed to low-calcium) soil, it develops aerial rootlets, it
is a large plant when mature, and it tends to produce sharply pointed lobes on its leaflets—all
different from poison oak.74,91
Toxicodendron radicans ssp. eximium (Figure 9.22) is a rare plant found in Big Bend National Park
and sometimes in tributaries of the Rio Grande River (Figure 9.23). It has unusual foliage with
lobing of the leaflets so deep and rounded that one might not suspect its toxic nature. Both the
leaves (Figure 9.24) and fruit have a soft, pubescent surface.74,91 The individual leaflets have a
deeply lobed configuration (Figures 9.22 and 9.24) that has been compared with that of a club on
playing cards.74
Because of the lobing and pubescence, some might try to classify this as a form of poison oak.
However, its large size, its range, its inclination to climb with aerial rootlets, its lack of a pseudover-
ticillate leaf pattern, and its rocky (higher calcium) habitat, all help to distinguish it from (eastern)
poison oak.74 While it has been reported rarely in other locations, it can be found regularly in Oak
Canyon in the Chisos Mountains of Big Bend National Park.74,91 There a small stream provides
adequate moisture in what is otherwise a largely desert terrain.
FIGURE 9.25 T. radicans ssp. divaricatum. (From: Guin, J.D., Beaman, J.H., Gillis, W.T., Recognizing the
toxicodendrons, J. Am. Acad. Dermatol., 4, 99–114, 1981. With permission.).
Toxicodendron radicans ssp. divaricatum (Figure 9.25) is primarily a Mexican taxon. Its range is
in Mexico along the western slope of the Rocky Mountains (Figure 9.26), but to the north it extends
into the mountains of southern Arizona.74,91 Its leaflets tend to be long and narrow, but they are
somewhat variable in the field. Leaflets may be either lobed or unlobed, the fruit is glabrous, and
the leaves are usually glabrous.74,91 Although both this subspecies and T. rydbergii are found in the
mountains of Arizona, this taxon does not extend to the mountains of northern Arizona where
T. rydbergii is found.74,91
Toxicodendron radicans ssp. orientale is distributed in Japan and the Kurile Islands and Sakhalin
in Russia (Figure 9.27). The plant grows in dense forests in Japan as part of the natural flora rather
than appearing in a weedy form after the ecology is disturbed as we see with American forms of
poison ivy.74 However, where a disturbance occurs, the plant becomes more abundant.
This subspecies is distinguished by its leaflets bearing tufts of hair in vein axils similar to T.
radicans ssp. radicans, but in T. radicans ssp. orientale the color is light colored to red brown.
Leaflets are entire but widest at or above the middle (obovate). The blade of the terminal leaflet is
1.2–1.7 times as long as it is broad and is 5–20 cm long and 3–12 cm wide. The base is cuneate.
Petioles are 1.5–11 cm long and petiolules are 0.5–3 cm long. The fruits are a flattened drupe,
5–6.5 mm broad, and the surface is papillose to short hairy.74 The northern form, said by some to
be nonclimbing, was regarded by Gillis to be the same except it had been too inadequately collected
to separate on this basis.74
This subspecies of T. radicans is indigenous to China and Taiwan (Figure 9.28), but some have
considered it to be the same subspecies as T. radicans ssp. orientale. However, Gillis separated it
because of the hispid nature of the fruit and the leaf measurements, both of which are somewhat
different. One might also argue that its montane nature is a bit different, as this subspecies grows
at elevations of 1150–3400 m, while T. radicans ssp. orientale is found at elevations as low as sea
level and as high as 1800 m. Only the two ssp. indigenous to Mexico which are found as high as
2500 and 2800 meters, are close to T. radicans ssp. hispidum.74
This subspecies also has the widest part of the leaflet at or above the middle (obovate). It is
attenuated at the base and is nearly twice as long as it is broad. Tufts of hair in vein axils are
hyaline to red brown. The fruit is a flattened drupe that is obliquely deltoid, some 5–6.5 mm wide.
The fruit surface is hispid with hairs almost 1 mm in length.74
Toxicodendron radicans ssp. barkleyi (Figure 9.29) is a Mexican taxon of T. radicans found in
eastern Mexico and Guatemala (Figure 9.30). It grows in very high calcium soil, with a calcium
content sometimes as high as 5700 ppm,74 and at elevations ranging from moderate to 2800 m,
second only to T. radicans ssp. hispidum.
The plant is either a shrub or climbing vine with aerial rootlets. Leaflets are entire or subentire
or with occasional notches. Leaflets are ovate to elliptic or elliptic-lanceolate. The upper leaf surface
is glabrate to velutinous, while the lower leaf surface is strigose, tomentose, or deeply pilose. The
terminal leaflet is 3–14 cm long and 1–10 cm broad. The petiole is 2–12 cm long and the terminal
petiolule is 0.5–5 cm long. Fruits are glabrous or puberulent and about 3–5 mm broad. The stem
of the growing season is pilose to wooly.74
an angle, like rabbit ears. Flowers and fruit are borne in the axillary position and leaf scars are U-
or V-shaped similar to that seen with poison ivy. The glabrous fruit is green when unripe and off-
white at maturity similar to that seen with poison ivy.91
Although T. vernix has traditionally been considered Rhus, it is certainly Toxicodendron.
Because the genera Rhus and Toxicodendron are closely related, it is not surprising that the two
are often confused. Plants with odd-pinnate leaves to be distinguished from poison sumac include
Rhus copallina (winged sumac), that unlike T. vernix has a winged rachis and terminal fruits that
are red or almost purple.98 R. typhina or staghorn sumac has 9–27 leaflets, pubescent branches,
serrated leaflets, and red, terminal fruit91; and R. glabra, which has 11–31 leaflets with serrated
borders, and red, terminal fruit.91 Certain benign sumacs in Rhus, for example, R. trilobata and R.
aromatica have leaves with three leaflets similar to poison oak. Distinguishing features include
short or absent petiolules, terminal fruiting structures, and reddish fruit.
FIGURE 9.34 Branches of T. rydbergii showing above the snow resemble the tines of a fork as seen during
winter in the Indiana Dunes region.
but not excessively, drained.74 Eastern poison oak prefers sandy soil of poor nutritional quality,74
and western poison oak is especially common in canyons where the shrub can find water. Poison
sumac is more likely to be in standing water in peat bogs and swamps, while most benign sumacs
grow in dryer soils. Unlike poison ivy and poison oak that are more common in disturbed sites,
poison sumac seems more abundant in remote, undisturbed locations, and it rapidly disappears
when the area is drained.
Winter recognition is more difficult, but it is still important because the nonleaf parts of these
plants can still induce dermatitis.99
The transition between the Caribbean and North American continent is abrupt with relatively
little overlap in plant taxons. Exceptions are the location of T. radicans in both Florida and the
extreme northwestern Bahamas and poisonwood (Metopium toxiferum) in the freeze-free zone of
the tip of Florida and the Keys as well as the Caribbean.
Mexico is another matter because that nation has two subspecies of T. radicans whose range
extends a very short distance into the southern counties of Texas and Arizona, while a third is self-
contained. Western poison oak, T. diversilobum, is predominantly found in the United States west
of the Rocky Mountains, but it extends for a very short distance into both British Columbia to the
north and Baja California in Mexico to the south.
Toxicodendron striatum (Figure 9.35) is a montane shrub or small tree, usually found at about 3000
ft. It is common in the Cobán region of Guatemala and south of Cartago in Costa Rica.2 Of the
reactive Anacardiaceae that are found in Central America, the montane Toxicodendron striatum is
the only Toxicodendron.
Leaves are pinnately compound with 11–15 leaflets, with those newly formed a bright red,
giving the tree a distinctive and recognizable appearance. The flowers borne in panicles are small
and white and the fruit is a small white drupe with a single seed.2
Certain species, particularly T. vernicifluum (Stokes) Barkley, have great economic importance as
sources of lacquer. This species is generally known in English as the Chinese lacquer tree, in
Japanese as urushi, and in Chinese as qi su.100 The lacquer exudate is initially milky but darkens
and thickens on exposure. It can be kept for long periods by storage in closed containers. Lacquer
has been used in China since before the beginning of the Christian era and reached its highest
development there during the Ming dynasty (1368–1644 A.D.). In Japan, the first records go back
to the fourth century. The art there reached its height during the seventeenth century. The process
of lacquering a piece may require several years, and the application of 300–400 coats.101
Although there are indigenous subspecies of poison ivy (T. radicans) in China and Japan,
Toxicodendron dermatitis is recognized as an industrial disease. Usually, it is confined to workmen
who gather the fresh sap or apply it, but there are occasional reports of dermatitis from handling
lacquered articles. One of the more dramatic cases is discussed by Ames102 concerning Japanese
damascene purchased in Kyoto that caused dermatitis in a number of steamship passengers. T.
succedanea (L.) Moldenke is a common source of dermatitis in New Zealand.103 This species also
has been used as a lacquer source in Indochina.78 In Japan, the wax from the fruit mesocarp, is
used much like beeswax. This has also been a component of varnishes, floor waxes, wax varnishes,
ointments, and furniture polish.104 The Bornean species with simple leaves, T. borneese is one of
the rarest toxicodendrons. When Gillis74 wrote his classic treatise on the genus, it had been reported
from only two localities in Sabah, but now is known also from Sarawak and Kalimantan.21 Beaman
tells that while one of their assistants was pressing a collection that had not previously been
recognized as this species, she broke out rather severely on the thighs where she had held the
specimens on her lap. Another member of the party who had been insensitive previously to such
allergy, used the end of a cut stem to mark his arm. The black stain was still present after almost
2 weeks and a distinct erythema resulted.20
9.28.12.2 Chemistry
In 1922, Majima105 isolated the sensitizing component of the Japanese lac tree and found it to be
a pentadecylcatechol, a compound with a benzene ring with hydroxyl substitutions in positions 1
and 2 and a side chain of 15 carbons in length containing varying numbers of double bonds. The
specific structures were extensively investigated by Charles Dawson and co-workers and others
who found that the Anacardiaceae contained plants with resorcinol (meta-dihydroxybenzene) sen-
sitizers as well as catechol (ortho-dihydroxybenzene) sensitizers. In fact, all dihydric benzenes are
potential sensitizers. Because most sensitizers in woods are quinones, it has been theorized that
the alk(en)yl catechols are converted to quinones, but this is not possible in the case of the
resorcinols. Furthermore, hydroquinones have not been found in the Anacardiaceae.106,107
These sensitizers are dihydroxy benzenes with long-chain alk(en)yl groups, and the most potent
sensitizers have unsaturated alkyl side chains. These side chains vary in length: 15 carbons for
poison sumac, poison ivy,70,108,109 poison wood,70 and cashew-nutshell liquid,110,111 17 carbons in
poison oak,108,112,113 Indochina lacquer, and Burmese lacquer.114
Poison ivy, with predominantly pentadec(en)yl catechols also may contain small quantities of
heptadec(en)yl (17-carbon side chains) catechols, and those (such as poison oak) with predomi-
nantly heptadec(en)yl catechols may have small quantities of pentadec(en)yl catechols (15-carbon
side chains).70
The alk(en)yl side chains have varying numbers of double bonds (from 0 to 3)106 and the
quantitative composition may vary somewhat with the geographic area of the collection70 or the
portion of the plant collected.115,116 Several authors have summarized some of the sensitizers found
NOTE:
The Anacardiaceae were covered in Plant Dermatitis, an issue of Clinics in Dermatology, Vol. 4,
edited by Drs. Guin and Beaman, in which we all contributed. We have updated the material and
cited the appropriate sources including many opinions of the sources. In that publication, the
Anacardiaceae of the Caribbean and Central America were written by Kenneth Lampe, Ph.D. of
South America; Inez Hurtado, Ph.D. of Africa; and David Whiting, M.D.; hyposensitization was
covered by Sue Watson, Ph.D. and several other authors included mention of the Anacardiaceae.
We are also grateful to Dr. Richard Kalish’s helpful suggestions on the clarity and accuracy of one
section in the book.
9.34 REFERENCES
1. Tyman, J. H. P., Cultivation, processing and utilisation of the cashew, Chem. Ind., 2, 59, 1980.
2. Lampe, K. F., Dermatitis-producing Anacardiaceae of the Caribbean area, Clin. Dermatol., 4, 171,
1986.
3. Bedi, B., Cashew nut dermatitis (report of two cases), Indian J. Dermatol., 16, 63, 1971.
4. Keil, H. Wasserman, D. and Dawson, C. R., The relation of hypersensitiveness to poison ivy and to
the pure ingredients in cashew nut shell liquid and related substances, Indust Med., 14, 825, 1945.
5. Watt, J. M., Medicinal and Poisonous Plants of Southern and Eastern Africa, E. & S. Livingstone,
Edinburgh, 1962, 43.
6. Tulipan, L., Dermatitis, Ind. Med., 5, 626, 1936.
7. Behl, P. N., Captain, R. M., Bedi, B. M. S., et al., Skin-Irritant and Sensitizing Plants Found in India,
Behl, Bombay, 1966, 28.
8. Srinivas, C. R., and Pasricha, J. S., Dermatological problems of workers employed in cashew nut
factories [letter; comment], Contact Derm., 22, 192, 1990.
9. Diogenes, M. J., de Morais, S. M., and Carvalho, F. F., Contact dermatitis among cashew nut workers,
Contact Derm., 35, 114, 1996.
10. Reginella, R. F., Fairfield, J. C., and Marks, J. G., Jr.,. Hyposensitization to poison ivy after working
in a cashew nut shell oil processing factory [see comments], Contact Derm., 20, 274, 1989.
11. Rosen, T. and Fordice, D.B., Cashew nut dermatitis, South. Med. J., 87, 543, 1994.
12. Marks, J. G., Jr., DeMelfi, T., McCarthy, M. A., Witte, E. J., Castagnoli, N., Epstein, W. L., and Aber,
R. C.,. Dermatitis from cashew nuts, J. Am. Acad. Dermatol., 10, 627, 1984.
13. Hamilton, T. K. and Zug, K. A., Systemic contact dermatitis to raw cashew nuts in a pesto sauce, Am.
J. Contact Derm., 9, 51, 1998.
14. Orris, L., Cashew-nut dermatitis, NY J. Med., 58, 2799, 1959.
15. Morton, J. F., The cashew’s brighter future, Econ. Bot., 15, 57, 1961.
CONTENTS
10.1 Introduction
10.2 Aralia
10.2.1 Aralia spinosa L.
10.3 Brassaia actinophylla ENDL.
10.4 Dendropanax
10.5 Fatsia
10.5.1 Fatshedera lizei (COCHET) GUILLAUMIN
10.6 Hedera
10.6.1 Hedera helix L.
10.7 Oplopanax
10.8 Panax
10.9 Polyscias
10.10 Schefflera
10.10.1 Schefflera arboricola HAYATA
10.10.2 Schefflera heptapleurum
10.11 Tetrapanax
10.12 References
10.1 INTRODUCTION
The plant family of Araliaceae comprises about 1325 species in 47 genera. Many of the species
grow in the Mediterranean area while others are widely cultivated as ornamental pot plants or held
in horticulture. Some Araliaceae species are equipped with secretory canals (oily glands) and
produce an aromatic smell when crushed.1 In their classification a subdivision into Schefflereae,
Aralieae and Mackinlayeae has been proposed. Typical characteristic of this family is the occurrence
of polyacetylenes (polyines).2 One of these polyacetylenes is the sensitizing falcarinol, that has
been found up to this time in the following species:
10.2 ARALIA
The genus Aralia comprises more than 36 species in North America, East Asia, and Malaysia.
10.4 DENDROPANAX
The genus Dendropanax comprises 60 species and is found in East Asia, the Malaysian peninsula,
and Central and South America. The common name for Dendropanax trifidus MAKINO (syn.
Gilibertia trifida MAKINO) is Kakuremino (Japan).
Only one species grows in Japan where it is cultivated in gardens and sometimes used in flower
arrangements.
The plant grows to 5 m in height and contains dendropanaxide, friedelin, epifriedelinol,
b-amyrin, and a glucoside.17 The cis-9,17-octadecadiene-12,14-diyne-1,16-diol was isolated and
identified as an antifungal constituent by Kawazu et al. in 1973.18 Contact dermatitis of the hands,
arms, cheeks, neck, and chin has been observed in Japan in people pruning and arranging the leaves
and branches of the plant.19-23
The main sensitizer was shown to be cis-9,17-octadecadiene-12,14-diyne-1,16-diol, a com-
pound structurally related to falcarinol (only one additional CH2OH-group) (Figure 10.1a). The
safe test concentration is 0.05 percent. The polyacetylene is a strong sensitizer as 4 out of 18
controls were actively sensitized during the investigation. Patch tests with the leaves produced
irritant reactions in 5 out of 18 individuals. Positive responses to ethanol extracts of Fatsia japonica
and cross reactions to urushiol were observed as well.23
10.5 FATSIA
The genus comprises three species and is native to Japan and South Korea. The common name for
Fatsia japonica (THUNB. ex MURR., DECNE et PLANCH.) (syn. Aralia japonica THUNB. ex
MURR.) is Japanese Fatsia. Fatsia is a popular indoor pot plant in Europe.
The leaves contain arolein, hederaguin, quercetin, idaeine, and b-profastin.1 Cases of allergic
contact dermatitis have not been described, however Oka obtained positive patch tests with the
leaves.23 A flare-up reaction developed in two controls who had been actively sensitized by a
Dendropanax trifidus extract when they were tested with the leaves of Fatsia japonica. Falcarinol
has not been detected so far, but the occurrence of a near related constituent is suspected.4
10.6 HEDERA
The genus Hedera comprises approximately 4 to 11 species. There are conflicting opinions regarding
its botanical nomenclature. Approximately one to three species are native to the temperate region;
In Great Britain, the second species is known as Canary Island ivy. The Americans named it
Algerian ivy to distinguish it from poison ivy of the Anacardiaceae family. Green Hedera was used
as poet’s crown and wreath of Bacchus, to whom the plant was dedicated.
The common name for Hedera helix L. subsp. helix is common ivy.
Common ivy contains up to 10 percent of saponins and is, therefore, used for washing. The
cooked leaves are used together with soda for washing clothes, too. French soaps as well as French
creams used for massages and for removing “disadvantageous curves” in females contain ivy
extracts. Occasionally the extract serves as a rubefacient.
The leaves contain the saponins a- and b-hederin, some coumarins, the alkaloid emetin, vitamin
E, and provitamin A as well as some hydrocarbon acids like chlorogenic, fumaric and coumaric
acid.1 Irritant and allergic contact dermatitis have been described since 1899. A list of all cases
with references described between 1899 and 1985 is given by Hausen et al. (135 cases, 31
references).5 More recently, 13 further cases were reported.24-26
The stalks, leaves, and roots contain falcarinol and didehydrofalcarinol (Figure 10.1b and 10.1c)
that have been shown to be the irritants and sensitizers in common ivy.5 Sensitization was achieved
experimentally by three different methods in guinea pigs.5 The safe test concentration of falcarinol
is 0.03 percent. As the leaves are broken during pruning, irritant contact dermatitis often occurs
because the leaves commonly contain more than 1 percent of the sensitizer. Didehydrofalcarinol
is a weaker irritant and sensitizer and, therefore, may be tested at 1 percent in petrolatum.
Falcarinol is chemically very active. It functions as an alkylating agent and can easily react
with amino or other protein groups and, thereby, facilitate covalent binding to the surface markers
of immuno-competent cells.
Falcarinol and didehydrofalcarinol also occur in the Apiaceae (syn. Umbelliferae) family.
10.7 OPLOPANAX
The genus Oplopanax comprises three species native to North America and Japan. The common
name for Oplopanax horridus (SM.) MIQ. (syn. Echinopax horridus SM ex J. G. COOPER) is
devil’s club. Contact with the prickles or a tincture of the leaves produces painful wounds, swelling,
itching, and blisters.27,28
10.8 PANAX
The genus Panax comprises six species. Panax ginseng is native to Korea, North China and parts
of the former Soviet Union.8 The common names for Panax ginseng C. A. MEYER are Chinese
ginseng and Asiatic ginseng.
Because wild ginseng is rare, today most of the material used as a remedy is cultivated in
China, Japan, Korea, Canada, and the United States. Ginseng contains the polyacetylenes
10.9 POLYSCIAS
The genus Polyscias (formally Nothopanax) comprises 150 species. Most of them are native to the
Pacific regions, for example, New Zealand, the Pacific islands (Hawaii), and Australia, but many
of them are also cultivated elsewhere in the world. The common name for Polyscias balfouriana
BAILEY (syn. Aralia balfouriana hort. SANDER) is Balfour polyscias and the common name for
Polyscias guilfoylei (BULL) L. H. BAILEY is Guilfoyle polyscias. Skin irritation has been men-
tioned by Morton35 and Arnold36.
10.10 SCHEFFLERA
The genus Schefflera comprises about 650 species in tropical and subtropical areas. Several members
are grown all over the world in nurseries as ornamental pot plants.
The common name for Schefflera arboricola HAYATA is Schefflera. Schefflera arboricola is native
to Taiwan, but grows abundantly in plant nurseries throughout Europe.
A case of eczema of the hands and forearms was described by Hammershøy in 1981.15 The
female nursery worker had handled Schefflera species only for two weeks when she developed the
skin lesions.
Patch tests were positive with the leaves and stems as well as with a short ether extract
(1 percent). All ten controls remained negative. The nursery worker also reacted to Brassaia
actinophylla, but not to Schefflera kyoto and Schefflera heptapleurum. The same patient was tested
again five years later, this time with falcarinol that had been isolated meanwhile by two chemists
from the ether extract of the leaves and stems.6,37 She reacted “strongly positive” to the constituent
but remained “negative” to the tests with the chemically near related polyacetylenes falcarindiol,
falcarinone, and dehydrofalcarinone.9
The common name for Schefflera heptapleurum (syn. Schefflera kwangsiensis) is umbrella tree.
A case of an acute vesico-bullous eruption on the back of the hands, arms, and neck was
observed by Calnan in 1981, in a man working with the umbrella tree in his garden.38 A test with
the leaf was positive at the 96-hour-reading.
Other Schefflera species of Australia are said to cause eruptions of the skin, too.39
10.12 REFERENCES
1. Karrer, W., Konstitution und Vorkommen der organischen Pflanzenstoffe, Birkhäuser Verlag, Basel,
1976.
2. Bohlmann, F., Burkhardt, and T., Zdero, C., Naturally occurring acetylenes, Academic Press, London,
New York, 1973.
3. Bohlmann, F., Niedballa, U., and Rode, K. M., Über neue Polyine mit C17-Kette, Chem. Ber., 99,
3552, 1966.
4. Boll, P. M. and Hansen, L., On the presence of falcarinol in Araliaceae, Phytochem., 26, 2955, 1987.
5. Hausen, B. M., Bröhan, J., König, W. A., Faasch, H., Hahn, H., and Bruhn, G., Allergic and irritant
contact dermatitis from falcarinol and didehydrofalcarinol in common ivy (Hedera helix L.), Contact
Derm., 17, 1, 1987.
6. Hansen, L. and Boll, P. M., The polyacetylenic falcarinol as the major allergen in Schefflera arboricola,
Phytochem., 25, 529, 1986.
7. Takahashi, M., Isoi, K., Kimura, Y., and Yoshikura, M., Studies on the components of Panax ginseng
II. On the etheral extract of ginseng radix alba, J. Pharm. Soc. Japan, 84, 752, 1964.
8. Shim, S. C. and Koh, H. Y., Polyacetylenes from Panax ginseng roots, Bull. Korean Chem. Soc., 4,
183, 1983.
9. Hansen, L., Hammershøy, O., and Boll, P. M., Allergic contact dermatitis from falcarinol isolated
from Schefflera arboricola, Contact Derm., 14, 91, 1986.
10. Hardin, J. W. and Arena, J. M., Human Poisoning from Native and Cultivated Plants, Duke University
Press, Durham, NC, 1974.
11. White, J. C., Dermatitis Venenata, Cupples & Hurd, Boston, 1887.
12. Muenscher, W. C., Poisonous Plants of the United States, Macmillan, New York, 1951.
13. Reynard, G. B. and Norton, J. B. S., Poisonous plants of Maryland in relation to livestock, Maryland
Agric. Exp. Stat. Tech. Bull., A10, 1942.
14. Kanngiesser, I., Phytonosen, Gartenflora, 59, 395, 1910.
15. Hammershøy, O., Allergic contact dermatitis from Schefflera, Contact Derm., 7, 57, 1981.
16. Mitchell, J. C., Allergic contact dermatitis from Hedera helix and Brassaia actinophylla, Contact
Derm., 7, 158, 1981.
17. Sakakibara, J., Kaiya, T., Taniguchi, K., and Yasue, M., Studies on the constituents of Gilibertia trifida
MAKINO, Nagoya-shiritsu Daigaku Yakugaku Kenkyo Nempo, 24, 27, 1976.
18. Kawazu, K., Noguchi, H., Fujishita, K., and Iwasa, J., Two new antifungal compounds from Dendro-
panax trifidus MAKINO, Tetrahedron Lett., 33, 3131, 1973.
19. Iwashige, T. and Kaneko, O., A case of contact dermatitis due to Dendropanax trifidus, Japan J.
Derm., 85, 489, 1975.
CONTENTS
11.1 Introduction
11.2 Ethnobotany of the Asteraceae
11.3 Asteraceae in Mexico, Historical and Modern Uses
11.4 Toxicity and Pharmacological Properties of the Major Classes of Sesquiterpene
Lactones from Asteraceae
11.4.1 The Sesquiterpene Lactones
11.4.2 Allergic Contact Dermatitis
11.4.3 Neurotoxicity
11.5 Medicinal Activities Reported from the Asteraceae Containing Sesquiterpene Lactones
11.5.1 Antitumor Activity
11.5.2 Anti-Ulcer Activity
11.5.3 Cardiotonic Activity
11.5.4 Antimigraine Activity
11.6 Summaries of Various Genera
11.6.1 Achillea
11.6.1.1 Achillea millefolium L.
11.6.1.2 Achillea nana L. (Achillea ageratifolia)
11.6.1.3 Achillea fragantissima
11.6.1.4 Ambrosia
11.6.2 Artemisia
11.6.2.1 Artemisia ludoviciana Nutt
11.6.2.2 Artemisia abrotanum
11.6.2.3 Artemisia herba-alba
11.6.2.4 Artemisia verlotorum
11.6.2.5 Artemisia monosperma
11.6.2.6 Artemisia tridentata
11.6.3 Cichorium intybusm
11.6.4 Elephantopus
11.6.4.1 Elephantopus spicatus
11.6.4.1.1 Ethnobotany
11.6.4.1.2 Pharmacology/Toxicology
11.6.5 Helenium
11.6.5.1 Ethnobotany
11.6.5.2 Helenium quadridentatum
11.6.5.2.1 Chemistry and Pharmacology
11.1 INTRODUCTION
The Asteraceae family, also known as the sunflower family, includes about 25,000 species. Plants in
this family include weeds (e.g., dandelions), ornamentals (e.g., sunflowers), and vegetables (e.g., lettuce,
chicory, and artichokes).1,2 Many plants of the Asteraceae are used for medicinal purposes throughout
the world. Unfortunately about 180 species are known to cause allergic contact dermatitis worldwide.3
There are about 380 genera with 3000 species currently (1994) recognized in this family in
Mexico. The principal reason for focusing a major review on Mexican Asteraceae (Compositae)
is their enormous importance in the popular medicine of Mexicans and persons with Mexican
ancestry and also to highlight their potential as contact dermatitis causing plants. Allergic contact
dermatitis is defined as inflamation and irritation of the skin owing to contact with an irritating
substance. Members of this botanical family include wormwood (Estafiate, Artemisia ludoviciana
ssp. mexicana), zoapatle (Montanoa tomentosa) and Mexican arnica (Heterotheca inuloides) and
are frequently sought by people who have health problems for which they do not want to consult
a doctor or a health center. For these reasons, it is important to the public health of these peoples
that the medical community have a summary of the pharmacological effects and potential to cause
contact dermatitis.
Although thousands of scientific articles have been published on natural products, each plant
has several hundred different natural products. The great majority of which have not been studied
for their contact dermatitis causing properties. Many of the plants used in folk remedies are
potentially hazardous and have chemical constituents that can elicit allergic contact dermatitis (e.g.,
Parthenium hysterophorus) or liver damage (e.g., pyrrolizidine alkaloids.)4
The review is limited to genera native to Mexico that are known to have contact dermatitis
properties and is divided into two major parts:
1. An initial description of the major types of chemical compounds and their major phar-
macological effects
2. Nine summaries of existing information about plant genera most widely used in popular
medicine of modern and historic Mexico
SQLs also form adducts with amino acids and proteins containing sulfhydral (SH) groups such
as cysteine.12,16 Previous investigators have reported an in vitro depletion of GSH by SQLs using
several tumor cell lines.23 Some SQLs also have demonstrated the capacity to deplete the levels of
GSH in vivo in different tissues.23 This fact is very important when considering the mechanism of
the action of sesquiterpene lactones.
11.4.3 NEUROTOXICITY
Several plant toxins have been associated with neurodegenerative changes in both the brain and
spinal cord. Until recently, no sesquiterpene lactones have been directly associated with neurolog-
ical disorders. However, in 1954, a specific neurological disease of horses commonly known as
chewing disease, was experimentally linked to the ingestion of large amounts of Centaurea repens,
a member of the Asteraceae with large quantities of SQL.23 Neuropathological examination of the
brain from the intoxicated horse revealed bilateral necrosis of the anterior globus pallidus and zona
reticulata of the substantia nigra. To pursue the hypothesis that SQL might produce neurotoxic
effects, Stevens and Riopelle24 conducted an in vitro neurotoxicity study. The growth of the neurites
was noted in the presence of the different SQL from Centaurea repens and the 50 percent toxic
dose (TD50) was estimated. On a molar basis, repin was 3 to 4 times more toxic than its C-17
isomer subluteolide and 4 to 10 times more toxic than acroptilin and the other SQL tested. In 1991,
Hostettmann and Hamburger25 studied the neurotoxic effects of SQL from yellow star thistle
(Centaurea solstitialis). Hostettmann and Hamburger25 reported that solstitialin cynaropicrin exhib-
ited toxicity to cultured rat fetal brain cells in a concentration-dependent manner and suggested
that these compounds could cause neurodegenerative disorders. In the laboratory, Robles et al.26,27
and flatulence. It was to be applied locally for scabies and itching of the face mixed with acuahuitl,
ehecapatli (not identified).46 During the twentieth century, it has been used as bitter tonic for nervous
disorders (nerves), hemorrhage, and for colic of the stomach and hypochondria. For an infusion
against hemorrhage, 20 g of the leaves and flowers are used. A decoction of 10 g per l of water
serves to cleanse wounds.47,48 It is a common weed in North America and known to cause strimmer
dermatitis.49
The methanolic extract was found to exhibit activity against mouse P-388 Leukemia cells in
vivo. Bioassay directed fractionation led to the isolation of three new sesquiterpenoids, achimilic
acids A, B, and C.50 Figure 11.1 has the chemical structure of these compounds. BDF1 male
mice at 6 weeks of age were inoculated intraperitoneally (i.p.) with 106 P-388 cells. Test
compounds were also injected i.p. as a single injection on the day following the tumor inoculation.
Antitumor activity was evaluated by the increase in life span (ILS) compared to that of the control
animals. The results showed that at 5 mg/kg dose, all 3 test compounds increased the life span
(ILS percent) The test compound results showed A to be 34 percent, B to be 39 percent and C
to be 35 percent). Doses of 20 mg/kg lost their effectiveness and doses of 50 mg/kg proved toxic
to the treated mice.
11.6.1.4 Ambrosia
Ambrosia is also known as ragweed and can cause contact dermatitis throughout the growing
season.53,54 Warshaw reported in 1996 that American male farmers, 40 to 65 years of age, are more
at risk than their female counterparts.95 They claimed a 20:1 male to female ratio. Different types
of SQLs are thought to ellicit contact dermatitis present in the Ambrosia species.54
11.6.2 ARTEMISIA
The genus Artemisia contains more than 200 species that have been reported from many parts
of the world and has been selected for remedies by cultures throughout the world for medicinal
properties. The reported active constituents of the genus include all the types of common natural
products of the Asteraceae: sesquiterpene lactones, polyacetylenes, flavonoids, essential oils
(monoterpenes), diterpenes, triterpenes, and coumarins. We have included aspects of recent
studies conducted with extracts of the genus to give an indication of the range of biologically
active compounds that could be found in the Mexican species if an exhaustive study were to be
conducted. (One particular compound from A. annua, artemisinin, with antimalarial properties
is not discussed because it appears to be restricted to Chinese species.) The sensitizing SQL are
ludovicins A, B, C.1
Four flavonols isolated from Artemisia abrotanum have been reported to possess spasmolytic
activity. These flavonols show a dose-dependent relaxing effect on the carbacholine-induced con-
traction of the guinea pig trachea.63
The EC50 values are as follows:
Artemisia herba-alba It is widely used for the treatment of diabetes mellitus. The compound alloxan
is used to produce a hypoglycemic state in experimental animals. Rabbits were fed daily plant
aqueous extract (0.39 g/kg) for 2 to 4 weeks.64 Similar experiments were conducted using male
adult Wistar rats (250 to 300 g).65 The results were similar for both rats and rabbits:
The extract of the aerial parts of the plant seems to have minimal adverse effect with a high
LD50 value. The LD50 graded doses of the aqueous extract were administered intraperitoneally to
mice (n=6, albino mice, 25 to 30 g). The LD50 value was observed at 4.49 g/kg body weight which
represents 20.54 g of the crude, powdered aerial parts material/l kg body weight.65
The relaxant effects of 7-O-methyleriodictyol, a flavone isolated from the aerial parts of Artemisia
monosperma, on various isolated smooth muscle preparations are shown next.
Also, the inhibition of contraction induced by known compounds such as acetylcholine and
oxytocin are consistent with the use of this plant in the treatment of certain gastrointestinal disorders.67
7-methoxy-5,3¢,4¢-trihydroxy-flavanone
This plant is frequently used as an anthelmintic, antiseptic, and analgesic. It is also known as
Chamiso hediondo (stinking sagebrush). Many of the compounds identified in this species have
notable pharmacologic activities, particularly the monoterpenes, sesquiterpene lactones, coumarins,
and flavonoids.
Sesquiterpene lactones include santonin, a potent anthelmintic used to treat ascaridiasis and
oxyuriasis. It acts on the ganglion cells of the worm to induce paralysis, so that the parasite can
be eliminated via the feces.71 Another SQL with anthelmintic properties is artemisin.
Several monoterpenes found in Artemisia tridentata have CNS-stimulatory effects (including
camphor, cineole, and thujone). Thujone, even when consumed in small doses, can cause convul-
sions and death owing to its psychomimetic effects.68
Cichorium intybusm is a weed that grows throughout the world that is commonly known as chicory.68
The roots are used to brew a coffee substitute and are also roasted to caramelize sugars that are
used with coffee drinks. The leaves are used in salads and are known as endive. The major allergens
are lactucin and lactopicrin, also found in lettuce (Lactuca sativa).1,69 In addition, lactucin and
lactopicrin have been reported to have neurotoxic properties.70,71
11.6.4 ELEPHANTOPUS
Elephantopus has approximately 12 species of herbaceous perennials in North and South America.
SQL and other biologically active compounds have been reported from this genus.
Elephantopus spicatus is the synonym for Pseudelephantopus spicatus C.F. Baker, Vernonieae.
11.6.4.1.1 Ethnobotany
The leaves are used for the treatment of cough and headache.11 Applied topically, they are employed
as an antipyretic, for the treatment of erysipelas, skin infections, and measles. A preparation made
from the roots is taken as a remedy for colic. The whole plant helps against diarrhea.9 It is one of
the most popular cough remedies of middle America.49
11.6.4.1.2 Pharmacology/toxicology
Elephantopus scaber has been used as a traditional remedy to cause dieresis, antipyresis, and to
eliminate bladder stones. This genus has been reported to contain the hydroxylated germacranolides,
molephantin and molephantinin, that also possess cytotoxic and antitumor properties.72,73 This plant
also contains phantomin and its cis-epoxide that have been reported to exhibit potent inhibitory
actions on Ehrlich ascites carcinoma and on Walker 256 carcinosarcoma cells.72,73
Pharmacological experiments on the plant extract were conducted by Poli et al.74 Oral admin-
istration (30, 60, 100, 300, and 600 mg/kg) and intraperitoneal injection (3, 10, and 30 mg/kg)
failed to modify the reaction time in the hot-plate test.
Intraperitoneal injection (300 and 600 mg/kg) in adult male Wistar rats significantly reduced
brewer’s yeast induced hyperthermia 1, 2, and 3 h after administration of both extracts. However,
oral administration of both extracts (300 and 600 mg/kg) failed to reduce edema induced by
carrageenan in the rat hind paw at 1, 2, and 4 h following exposure.
In addition, the aqueous (300 and 600 mg/kg, p.o.) extract significantly decreased intestinal
transit in mice. The ethanolic extract, up to 6 g/kg, did not produce significant modifications in the
behavior of mice. Intraperitoneal (i.p.) injection of both aqueous (0.03 to 3 g/kg) and alcoholic
(0.1 to 3 g/kg) extracts induced writhing, loss of muscle tone, ataxia, prostration, and death. The
estimated LD50 in adult male Swiss Webster mice was greater than 2 g/kg i.p. and after oral
administration was greater than 6 g/kg. These acute toxicity experiments reveal a low toxicity for
the plant extract.75
11.6.5 HELENIUM
Helenium is a genus with about 40 species of annual and perennial herbs. A large number of SQL
with pseudoguainolide and germacranolide skeletons have been reported from this genus, many of
the SQL being very toxic.
11.6.5.1 Ethnobotany
Helenium mexicanum (synonym for Gomphrena decumbens, fide B. Ortiz de M., Heliantheae)/
Sneezeweed (engl.)/Ueuei itzontecon (nahuatl)—This plant is taken orally if a person is very sick,
the stomach hurts, the heart seems faint, the temples throb, the nerves quiver, or in case of fever
or for pus in the genital organ.44
Amo9 lists the following uses for fever, catarrh, as a diuretic and an insecticidal and for testicular
inflammations. Martinez47 mentions the plant is used to provoke sneezing, as a diuretic, and against
colic and fever.
Structure of Helenalin
11.6.7 MONTANOA
Montanoa is a small genus of large shrubs in Mexico. Montanoa has a variety of natural products,
the most important being diterpenes.
11.6.8 PARTHENIUM
Parthenium is a small genus of approximately 16 species of shrubs, herbaceous perennials, and
annuals. A wide variety of biologically active SQL are found in the genus.
11.6.8.1.1 Ethnobotany
It is one of the Asteraceae that is used medicinally by a large number of indigenous and mestizo
groups of Mexico. Villada84 lists the plant as a remedy for malaria, for neuralgia, and as a vermifuge.
It is employed by the Mixe Indians in the form of baths to cure fever and body pain,85 and by the
Huastec to treat sores, muscular aches, epilepsy, and fever11,48 for similar uses from other areas.
11.6.8.1.2 Phytochemistry
The species is rich in sesquiterpene lactones with parthenin as the main compound. Parthenin and
ambrosin are known to be the major allergens for contact dermatitis.87
11.6.8.1.3 Pharmacology
Parthenin, the main sesquiterpene lactone of P. hysterophorus, was shown to possess in vitro and
in vivo (hepatic amoebiasis in hamsters) amoebicidal activity. The MIC50 in vitro is 10 to 12 mg/ml,
a value that is comparable to that of metronidazole. However, in vivo parthenin (ED50 40 mg/kg)
was less effective than metronidazole. Also, the compound was shown to be quite toxic.86
11.6.8.1.4 Toxicology
In hamsters, a 40 mg/kg dose proved toxic to 2 out of 7 animals. The LD50 and MLD doses in
mice were established as 450 and 600 mg/kg, respectively.86 The plant has now become a pantropical
pest and a strong elicitor of allergic contact dermatitis.88
Known as the dandelion, Taraxacum officionale derived its name from the French “dent de lion,”
because of its immature seeds and notched leaves resembling lion’s teeth.1,69,87 The allergen is a
sesquiterpene lactone linked to glucose via an ester linkage known as taraxinic acid (1-O-b-
glucopyronoside).
11.6.10 TITHONIA
Tithonia is a small genus of less than 10 species in Mexico and Arizona that has been delimited
variously. Tithonia includes both large herbs and shrubs.
11.6.10.1.1 Ethnobotany
It is one of the most frequently seen plants in gardens of the tropical areas of Mexico and seems
to be an important, but ethnobotanically little known medicinal plant in these regions. With the
Lowland Mixe, it is used orally against malaria and other forms of fever, and used topically to treat
11.7 CONCLUSION
In this review, aspects of recent reports of the pharmacology and toxicology and allergic contact
dermatitis of plant extracts and recently identified chemicals from the plant family Asteraceae used
by Mexicans and Mexican Americans/Chicanos are discussed. The number of plant species in this
family in Mexico and the Southwest is numbered in the thousands, and each species undoubtedly
contains hundreds of untested compounds with biological activity. It is impossible at this point to
list all of these activities; instead, the main emphasis has been placed on reviewing the most widely
used herbal remedies to give medical practitioners some idea of the possible physiological effects
of the herbal remedies used by their patients. In turn, this will raise a warning flag whenever
potential hazardous risks of contact dermatitis are present. Contact dermatitis classically involves
men older than 40 years with a history of outdoor activities. Interestingly, women and children are
less frequently sensitized.
Usually, a single small area of the exposed body is involved for some time. Then, a more
widespread eruption takes place that involves unexposed areas of the body. The dermatitis reaction
usually disappears in the winter. Flowers and leaves are usually more potent sensitizers than stems.93
The prevalence of SQL-induced allergic contact dermatitis is not known, but it has been reported
in Europe, Latin America, India, Japan, and Australia. It is a worldwide problem. Avoidance of
SQL containing plants is the best effective treatment but, of course, that is not practical especially
when these same plants are used for medicinal purposes. While no widespread studies of oral
hyposensitization have been reported, several small studies have reported success using patch test
reactions. A protocol developed by Storrs employs the combination of PUVA therapy and oral
prednisone.1
It is important to note that many of the natural products of the Asteraceae have the capacity to
form adducts with glutathione. This reaction will in turn stimulate or inhibit the p-450 mediated
metabolism of xenobiotics, and is relevant particularly to medical practitioners because these effects
may profoundly change the physiological effects of the drugs they are prescribing for their
patients.93,94
11.8 ACKNOWLEDGMENTS
We wish to acknowledge Dr. Ortiz de Monrtellano for his contributions and sharing of the ethno-
botany data presented in this review.
CONTENTS
12.0 Abstract
12.1 Introduction
12.2 Betula
12.2.1 Molecular and Immunological Characterization of Bet v 1,
the Major Birch Pollen Allergen
12.2.1.1 Bet v 1-Specific T-Cells: Epitope Mapping and T-Cell
Receptor Characterization
12.2.1.2 Comparison of Immunological Properties of rBet v 1
and nBet v 1
12.2.1.3 Animal Models for the Study of Birch Pollen Allergy
12.2.1.4 Models for Specific Immunotherapy of Birch Pollen Allergy
12.2.2 Bet v 2, Birch Pollen Profilin
12.2.3 Bet v 3, a Novel Calcium-Binding Protein
12.2.4 Bet v 4, a Two EF-Hand Calcium-Binding Protein
12.3 Carpinus
12.3.1 Car b 1, the Major Hornbeam Pollen Allergen
12.4 Corylus
12.4.1 Cor a 1, the Major Hazel Pollen Allergen
12.5 Alnus
12.5.1 Aln g 1, the Major Alder Polen Allergen
12.6 Conclusions
12.7 Acknowledgments
12.8 References
12.0 ABSTRACT
The early flowering trees of the Betulaceae produce large amounts of wind-spread pollen that
represent an important source of inhalant allergens during spring time. These pollen allergens are
capable of inducing IgE-mediated symptoms in susceptible atopic individuals. The major birch
pollen allergen Bet v 1 is by far the best studied allergen at both the molecular and immunological
levels. It was the first pollen allergen whose cDNA sequence was determined. The T-cell epitopes
of Bet v 1 have been mapped, several models for specific immunotherapy have been suggested,
and its crystal structure has been elucidated. Based on sequence similarities Bet v 1 has been placed
among the pathogenesis-related protein family 10 whose members have been described in both
dicots and monocots. A phylogenetic tree has been constructed based on betv1 homologous genes.
The major pollen allergens of alder, hazel and hornbeam, Aln g 1, Cor a 1, and Car b 1, respectively,
showed similar molecular and immunological characteristics to Bet v 1. The strong interest of
molecular allergology in pollen proteins has also fostered progress in plant molecular biology. Bet
v 2 has been identified as the first plant profilin and two distinct calcium-binding proteins from
birch pollen, Bet v 3 and Bet v 4, were discovered.
12.1 INTRODUCTION
Species of the Betulaceae, or the birch family, are trees and shrubs commonly found throughout
the northern hemisphere. They have numerous small and inconspicuous unisexual flowers, with a
highly reduced perianth (Figure 12.1). The male flowers aggregate into an inflorescence known as
a catkin or an ament. The female flowers form a catkin or a small head. All the betulaceous species
are monoecious and pollinated by wind. They produce copious quantities of pollen that cause hay
fever allergies.1-4 Many betulaceous species bloom in the early spring before the appearance of
leaves that facilitates wind pollination and increases the quantities of their airborne pollen.
12.2 BETULA
Betula (common name: birch) is composed of approximately 40 species. The taxonomy of the
genus is controversial owing to common interspecific hybridization and introgression,24-26 resulting
in a high level of morphological variability. The chromosome numbers vary substantially among
species with 2n = 28, 56, 70, 84, and 112.6
Species of Betula are trees or shrubs with white to dark brown barks. Winter buds are sessile
with several imbricate and smooth scales. Leaves are variously shaped, mostly ovate to deltoid,
with serrate to doubly serrate margins and 6–14 lateral veins. Staminate catkins are drooping and
mostly terminal on branches, solitary or two to five in a racemose cluster. Pistillate catkins are
erect, axillary in position, solitary, and cylindric to ovoid in shape. The catkins consist of numerous
flowers, three per scale, and lacking sepals and petals. Staminate flowers have two to three stamens,
and the pistillate flowers have a two to three carpellate pistil, with the stigma one to three lobed.
Scales of the infructescences are three lobed and the shape of the scales differs among species.
Fruits are small samaras with two lateral membranaceous wings. Birches show many morphological
similarities with alders, differing mostly in their infructescences. Birches have three lobed and
deciduous scales (vs. five lobed and persistent in alders), and three (vs. two) fruits per scale.
Furthermore, the winter buds of birches are sessile (vs. stipitate or subsessile).
The cloning and high level expression in E. coli and purification of Bet v 1 and related tree pollen
isoallergens formed the base for a great variety of immunological studies.48,49 IgE production by
B-cells requires the help of allergen specific T-cells. These T-cells are activated by highly immu-
nogenic peptide fragments of the allergens which are presented by antigen processing cells in the
the context of MHC class II molecules. T-cell clones (TCCs) established from the peripheral blood
of birch pollen allergic donors were used to map the T-cell epitopes of Bet v 1 by the use of
overlapping synthetic peptides. Seven different T-cell epitopes were defined that were distributed
over the whole molecule.50 It was clearly demonstrated that single allergic individuals display
several distinct T-cell specificities and that some of these represent immunodominant epitopes.51
Epitope specificities of TCCs from nonatopics were identical to those found in allergic individuals.
In allergic individuals, however, the activation of allergen-specific TCCs led to a higher ratio of
produced IL-4 vs. IFN-g that is responsible for IgE production.52 T-cell receptor (TCR) a- and
b-chain sequences of Bet v 1-reactive human CD4+ TCCs specific for a C-terminal minimal epitope
showed a striking heterogeneity in length and amino acid composition in their third complemen-
tarity determining regions (CDR3s).53 Nevertheless, all TCCs showed an arginine residue in the
N-terminal region of their TCR b-chain CDR3 loops. TCR a- and b-chain sequences of human
CD4+ TCCs specific for three additional immunodominant Bet v 1 epitopes showed that each
antigenic peptide derived from Bet v 1 was capable of selecting different characteristics in the
responding TCR repertoire.54 Allergen-specific TCCs can persist for years, evidence for which
could be monitored in blood, but also in the target organ of the allergic disorder for up to four
years.55
rBet v 1 has proved to be equivalent to natural Bet v 1 (nBet v 1) in a number of applications. rBet
v 1 produced in E. coli allowed accurate in vivo and in vitro diagnosis of more than 95 percent of
birch pollen allergic patients. No false positive results were obtained in in vitro assay systems such
as ELISA or Western blot, or by skin testing such as skin-prick or intradermal testing.56 In addition,
rBet v 1 also produced postive skin test reactions in patients with allergies to apples, cherries, or
hazelnuts that demonstrated its immunological relationship to food allergens.57 rBet v 1 was equally
potent as nBetv 1 to induce nasal reactions in birch pollen allergic patients with rhinitis and bronchial
reactions in patients with asthma.58
12.4 CORYLUS
Corylus (common name: hazel) consists of approximately 13 species widely distributed in the
northern hemisphere, with about 7 species in eastern Asia, 1 in western Asia, 1 in the Himalayas,
2 in Europe, and 2 to 3 species in North America. The taxonomy of Corylus, especially those from
eastern Asia, is still controversial. Chromosome numbers are reported to be 2n = 22 and 28.6,88
Furlow88 discussed the possibility of the diploid counts as 28 being erroneous.
Species of Corylus are shrubs or trees with grayish brown bark. Winter buds are sessile with
several smooth and imbricate scales. Leaves are borne on long and short shoots, mostly broadly
ovate to sometimes ovate with often cordate bases and doubly serrate margins. Leaf surfaces are
usually pubescent or bear glandular hairs, especially on the petiole. Staminate inflorescences are
solitary or in a racemose cluster. Pistillate inflorescences are highly reduced and composed of one
to several flowers. Staminate flowers are three per scale with four stamens. Pistillate flowers are
enclosed within a bud at anthesis with only the styles exposed. The fruit is the largest nut of the
birch family and usually enclosed or partially enclosed by an involucre.
Recognized are three sections: section Corylus, section Tuboavellana, and section Acan-
thochlamnys.17,89,90 Section Corylus includes species with a short involucre of two bracts, such as
12.5 ALNUS
Alnus (common name: alder) has about 25 species that occur primarily in the northern hemisphere
and extend into northern Africa in the Old World, and into Central America and the Andes in the
New World. Recognized are three subgenera: subgenus Alnus, subgenus Alnobetula, and subgenus
Clethropsis. Chromosome numbers are 2n = 14, 28, 42, and 56, with x = 7.6,88
Species of Alnus are trees or shrubs with light gray to dark brown barks. Winter buds are
stipitate to subsessile with two to several scales or naked. Leaves are borne on short and long
shoots, ovate, obovate, to elliptic in shape, and irregularly serrate, doubly serrate, or dentate at the
margin. Staminate catkins aggregate into a racemose cluster of three to five. Pistillate catkins are
solitary or in a cluster of two to many. Staminate flowers are three per scale, usually with four
stamens. Pistillate flowers are two per scale. Infructescences are cylindric in shape with five lobed,
thickened, and persistent scales. Fruits are small samaras with two lateral wings.
Species of subgenus Alnus have stipitate winter buds covered by two valvate scales. Their
inflorescences are several in a racemose cluster and developed during the growing season prior to
anthesis. Subgenus Alnobetula has subsessile winter buds with several imbricate scales. The inflo-
rescences are formed the season before anthesis. Subgenus Clethropsis is mostly Asiatic with one
North American species, A. maritima. This subgenus is characterized by its naked buds, blooming
in the fall, and solitary pistillate inflorescences in leaf axils. Copious pollen is produced by the
alder species in the early spring (subgenus Alnus), spring (subgenus Alnobetula), or late in the
summer (subgenus Clethropsis).
12.6 CONCLUSIONS
The detailed study of the major birch pollen allergen Bet v 1, in particular, shows how the interest
in pollen allergens has made progress possible in plant molecular biology. Molecular allergology
has speeded the research of one pollen protein that led to its production as a recombinant protein
and its crystallization.37,44,48,49 Although the function of Bet v 1 is still under discussion, it was
classified as a pathogenesis-related protein belonging to a new class of intracellular PR-proteins.34,41
A subclass of betv1 genes was discovered in birch cell suspension cultures cultivated with bacterial
and fungal pathogens.39 Betv1-homologous sequences, described from a wide variety of species
and genera, were used to construct phylogenetic trees giving another example of how medicine
and botany can interrelate.19 The discovery of several different naturally occurring Bet v 1 isoforms
and their different immunological properties led to a synthetic molecule harboring characteristics
of different isoforms.40,64,65 This designer allergen will form the basis for a clinical study of a new
concept for specific immunotherapy.65 The interest in the second birch pollen allergen, Bet v 2,
fostered the discovery of the first plant profilin that in term, ignited the interest in profilins and
their functions in other plants such as tobacco, corn, and tomato.66,73,75,80 Pure recombinant allergens
are not only excellent tools for diagnosis, study, and immunotherapy of type I allergic diseases,
but they can also be used to study the protein’s function in plants. rBet v 4 introduced into pollen
tubes was able to stop cytoplasmic streaming in its vicinity.82 These studies are examples of how
molecular medicine and plant molecular biology and taxonomy can produce results of mutual
interest and of importance to the advancement of science in both disciplines.
12.7 ACKNOWLEDGMENTS
This study was supported by the Austrian Science Foundation (S06707) to Scheiner and the National
Science Foundation (DEB-9726830) to Wen. We thank Dr. Zhi-duan Chen for permission to use
his pollen photographs and Chris Way for making botanical illustrations.
12.8 REFERENCES
1. Chamberlain, C., Hayfever in the Pacific Northwest, Ann. Otol. Rhinol. Laryngol. 36, 1083, 1927.
2. Lewis, W. H. and Elvin-Lewis, P. F., Medical Botany, Plants Affecting Man’s Health, John Wiley &
Sons, New York, 1977.
3. Lewis, W. H., Vinay, P., and Zenger, V. E., Airborne and Allergenic Pollen of North America, Johns
Hopkins University Press, Baltimore, MD, 1983.
CONTENTS
13.1 Introduction
13.2 Phytochemistry, Chemotaxonomy, and Pharmacology of the Hydrophyllaceae
13.3 Allergenic Chemistry of the Hydrophyllaceae
13.3.1 Phacelia
13.3.2 Wigandia
13.3.3 Turricula
13.3.4 Nama
13.4 Acknowledgments
13.5 References
13.1 INTRODUCTION
The family Hydrophyllaceae is comprised of 250 species in 18 genera with cosmopolitan or subcos-
mopolitan distribution except in Australia. The family is especially found in arid zones of southwestern
North America. Hydrophyllacae are normally herbs or shrubs with glandular hairs and trichomes on
the leaves that are usually rough and odoriferous. There are anecdotal accounts of some species of
the Hydrophyllaceae causing blisters, irritations, and, in some cases, severe dermatitis.
Molecular data1 suggests that the Hydrophyllaceae, with the exception of the genus Hydrolea,
form a monophyletic group nested with the woody tropical Boraginaceae. These phylogenetic
considerations also suggest that within the Hydrophyllaceae, there is a division between the woody
clade that includes Wigandia, Eriodictyon, and Turricula and a large herbaceous clade containing
Nemophila, Phacelia, and other smaller genera.
Some aspects of the secondary chemistry of the Hydrophyllaceae have been proposed to be of
utility in delineating some phylogenetic relationships. The distinct flavonoid chemistry (19–26,
Figure 13.4) of Nama rothrockii and N. lobbii suggests that these species are closer allied to
Eriodictyon than either one is to Nama.8
FIGURE 13.4 Flavonoid chemistry useful in the phylogeny of the genus Nama.
FIGURE 13.7 A sesquiterpene and two flavonoids isolated from Wigandia kunthii.
have been noted to produce dermatitis: Phacelia brachyloba, P. campanularia, P. minor, P. pedi-
cellata,14 P. crenulata, P. grandiflora,14,15 P. parryi, P. viscida,15 and P. infundibuliformia.16 However,
some species of Phacelia were found not to elicit the allergic response.14
The chemistry associated with the allergic response caused by Phacelia has been studied
extensively in the species that occur in the North American southwest. Phacelia campanularia,
(Figure 13.8) an annual of the California Mojave Desert, contains the novel farnesylhydroquinone
derivatives, the phacelioids 43, 44, and 45, and 46 in minor amounts.17,18 These compounds were
tested on the shaved skin of guinea pigs sensitized with the crude extract of P. campanularia; of
these compounds, 45 and 46 were recognized as the most active eliciting a response with as little
as 0.002 mmol. Compounds 43 and 44 are active to a smaller extent, probably owing to their facile
polimerization.
The glandular trichomes of P. pedicellata contained two major phenolic compounds 47 and
48. Compound 47 is the principal dermatotoxin18; it acts as an irritant in unsensitized animals at
concentrations of 0.55 mmol and causes an allergic reaction in sensitized animals at a concentration
of 0.061 mmol. Compound 48 is irritating at 1.5 mmol but does not elicit allergic reactions.
Phacelia crenulata, commonly known as desert heliotrope is responsible for most of the
dermatitits caused by Phacelia. It occurrs in the arid southwest of North America (California,
Arizona, Utah, and Nevada), and during spring, people walking among the blooms develop der-
matitis on the ankles and legs. P. crenulata var. funerea J. Voos ex Munz is characterized by a floral
stem of bluish-purple flowers that coil into a fiddleneck. The oily glandular secretions contain a
major constituent, geranylhydroquinone 49.17,19
Geranylhydroquinone (Figure 13.9) is a powerful allergen. It sensitized 19 of 21 human test
subjects at a nonirritating concentration of 0.5 percent. At 4.0 percent concentration, it produced
FIGURE 13.10 Geranylgeranylhydroquinone, the major allergen in the trichome secretions of Phacelia
minor.
bullous reactions. There are some similarities between geranylhydroquinone and the poison oak
and poison ivy pentadecylcatechols and heptadecylcatechols urushiols respectively; but comparative
patch testing in urushiol-sensitive individuals with geranylhydroquinone shows that there is no
cross-reactivity between the two allergens. Dried leaves of P. crenulata do not elicit an allergic
response due to the chemical unstability of geranylhydroquinone, decomposing readily to a dark
nonreactive compound in the presence of air.
Phacelia minor (Harv.) Thell., common to the coastal mountains of southern California, is
similar to P. crenulata but differs in flower morphology being urn-shaped in P. minor with more
round leaves. Similar to P. crenulata, the oily secretions from the glandular trichomes of P. minor
contain a major allergenic principle that has been elucidated to be geranylgeranylhydroquinone 50
(Figure 13.10). A minor constituent in P. minor is 1-oxofarnesylhydroquinone 46.17,19,20 Studies
with guinea pigs show that 50 is a potent sensitizer and is cross reactive with geranylhydroquinone.
A dose of 0.01 mmol of 50 produces an erythema on at least 1/2 of the animals sensitized to 50 or
46. A dose of 0.02 mmol of 46 elicited a reaction in at least 1/2 of the treated animals. In nonsensitized
animals, a dose of 0.08 mmol and 1.5 mmol of 50 and 46, respectively, is needed to cause an irritation.
Another allergenic species of Phacelia is P. parryi that occurs also in the coastal mountains
and foothills of southern California extending south into Baja California, Mexico. The major contact
allergen present in the trichomes is geranylgeranyhydroquinone 50 and a minor constituent is the
hydroquinone 46.17,20
Endemic to the northern part of Baja California, Mexico, Phacelia ixodes Kellog is cited in
the anecdotal literature as a toxic species to the skin. This species is notably densely covered with
glandular trichomes containing a complex mixture of phenolic compounds (Figure 13.11). The
major compound isolated from these glandular trichomes was geranylhydroquinone 49. The second
most abundant constituent is a new phenolic compound, 3-geranyl-2,5-dihydrophenyl acetate 51.
Also, a major constituent was geranylbenzoquinone 52, an oxidation product of geranylhydro-
quinone. In amounts equal to 52 was 2-geranyl-6-hydroxy-4-methoxyphenyl acetate 53. The minor
constituents found were 2-geranyl-4-hydroxyphenyl acetate 54 and 6-hydroxy-2-methyl-(4-methyl-
3-pentenyl)-chromene 55, the latter compound had been isolated previously from the tropical tree
Cordia alliodora (Boraginaceae) and named cordiachromen A.21 One distinct feature of P. ixodes
is that the glandular trichome exudate is not typically transparent and colorless, but yellow and
opaque. This is owing to the presence of a flavone that was identified as 6,7-dimethoxyapigenin
56 and found previously in the Labiateae and as a glycoside in the Asteraceae and Scrophulariaceae.
Compound 53, like 49, mentioned earlier, is an irritant and an allergen, but 51 is only an irritant.
Compounds 54 and 55 have not been tested for allergenic properties but at 2 mmol do not cause
an irritation.
Several species of Phacelia have been screened for the presence of hydroquinones and it has
been reported that P. viscida contains geranylhydroquinone 49, while P. distans, P. cicutaria, P.
fremontii, and P. minutiflora do not.18 The former species has been reported to be allergenic and
cross reactive, but P. distans apparently does not cross react with other species of Phacelia.
13.3.2 WIGANDIA
Another genus that has been associated with dermatitic reactions in the Hydrophyllaceae is the
genus Wigandia. There are five species in tropical America. These are shrubs and trees used in
subtropical garderning. Wigandia caracasana var. macrophylla is used as an ornamental in the
southwest. There are several varieties, some with stinging hairs, painful to the touch; others lack
them. There is only one published report of allergies caused by this plant, but there are several
personal communications with accounts of contact dermatitis.22,23 One case stands out about a group
of students that developed dermatitis on the hands and arms after exposure to a planted stand of
Wigandia in a botany class.24
Wigandia caracasana leaves and stems are covered with stalked glandular trichomes that exude
oil droplets. Several irritants and dermatitis elicitors have been isolated from these glandular
exudates, and some are unusual compounds.24 From the plant, five major chemicals were isolated
and their dermatitic potential evaluated (Figure 13.12). The most potent irritant and contact allergen
in Wigandia is 2,3-dimethoxygeranylbenzoquinone (quinone A) 57. It is one of the most potent
contact allergens in the Hydrophyllaceae and as active as pentadecylcatechol found in poison ivy.
A second quinone was isolated, 2-hydroxy-3-methoxygeranylbenzoquinone (quinone B) 58 and,
surprisingly, the absence of the methoxy group from carbon-2 practically deactivates the compound.
Thus, quinone B is neither an irritant or an allergenic. Another allergenic compound isolated from
W. caracasana, and previously isolated from W. kunthii, is wigandol 59.12 Wigandol is both an
irritant and an allergenic, but it is 10 times less active than quinone A. Methyl wigandol 60, also
isolated from W. caracasana as the major constituent of the trichome exudate, is not an allergenic.
Farnesylhydroquinone 61, also in the exudate and previously reported in W. kunthii, is as potent
as quinone A.
13.3.3 TURRICULA
The genus Turricula is monophyletic with T. parryi being the only species occurring in the North
American southwest and used as a cultivated ornamental, and there is only one report on its
allergenic properties causing severe dermatittis to many persons,25 but there are anecdotal accounts
from field botanists as to the hazards of this plant.26 Stems and leaves are densely covered with
glandular hairs that secrete oils that contain a complex mixture of phenolic compounds,26 the
analysis of these glandular secretions yielded as a major constituent a yellow oil, turriculoic acid-
A, that can be separated into two stereoisomers 62a and 62b. The second most abundant constituent
is a yellow oil, turriculoic acid-B, that is a mixture in a ratio of 2:1 of the E and Z stereoisomers
63a and 63b. The other constituents in decreasing order of relative amount are, turriculoic acid-C
64, turriculoic acid-D 65, the alcohols turriculol-E 66 and turriculol-F 67, and the prenylated benzoic
acid 3-farnesyl-p-hydroxybenzoic acid 68 (Figure 13.13).
Compounds 62-68 were tested on guinea pigs for their potential to elicit allergic contact
dermatitis. None of the compounds tested were irritant to nonsensitized animals at the highest dose
tested of 0.5 mg, and only compound 64, elicited allergic skin erythemas in sensitized animals. A
dose of 0.15 mg (0.5 mmol) is required to give a response in 5 out of 10 animals treated. This
shows that compound 64 is not a particularly strong allergenic hydroquinone when compared with
some of the hydroquinones from the Phacelia species. However, it is clear that the allergenic
properties of Wigandia are related to these compounds.
13.3.4 NAMA
Of the remaining 15 genera in the family, only 1 other genus has been reported to contain at least
a species that causes blisters upon contact, the genus Nama,14 of which there are 45 species
distributed in the southwest of North America, and tropical America and 1 species in Hawaii. The
reported species with blistering properties is Nama hispidum var. spathulatum, and occurs in the
North American southwest and northern Mexico. There are no other reports on the allergenic activity
of any Nama species. Several species of Nama have been collected and investigated for the chemistry
and insecticidal properties, including N. hispidum, and their handling has not resulted in injury to
the skin.
In summary, the chemistry associated with the irritations and contact dermatitis that plants in
the family Hydrophyllaceae cause in humans and animal models is a series of prenylated hydro-
quinones, the phacelioids, with similar structural features to those of the pentadecyl and heptadecyl
catechols in poison ivy and poison oak (Toxicodendron sp., Anacardiaceae). These hydroquinones
appear to be unique to this family and have only been reported in a variety of marine organisms
that include seaweeds, sponges, and urochordates.
The chemical similarities of the phacelioids with the urushiol constituents have led researchers
to propose that both types of compounds possess similar modes of action and act upon the immune
system in an analogous manner. A hypothetical mechanism of action has been proposed, and it
assumes that the phacelioids undergo oxidation to yield the corresponding benzoquinones that act
13.4 ACKNOWLEDGMENTS
We wish to acknowledge the extensive collaboration with Dr. William Epstein (UCSF) in all aspects
of the clinical testing of natural allergens, and the contributors of Dr. Gary Reynolds (UCI) to the
knowledge of the chemical nature of irritants and allergens in plants. We also thank the National
Institutes of Health (NIAID) for Financial Support.
13.5 REFERENCES
1. Ferguson, D. M., Phylogenetic analysis of Hydrophyllaceae and a preliminary study of biogeographic
patterns and life history evolution, Am. J. Bot., 83, Suppl. 6, 155, 1996.
2. Caceres, A., Figueroa, L., Taracena, A. M., and Samayoa, B., Plants used in Guatemala for the
treatment of respiratory diseases 2. Evaluation of activity of 16 plants against Gram-positive bacteria.
J. Ethnopharmacol. 29(1), 77, 1993.
3. INN (Instituto Indigenista Nacional), Aspectos de la medicina popular en el area rural de Guatemala,
Guatemala Indíg. 6, 1, 1971.
4. Horner, P. and Scora, R., Leaf hydrocarbons of Phacelia species (Hydrophyllaceae), Phytochemistry,
22(11), 2489, 1983.
5. Roitman, J. and Wollenweber, E., b,b-dimethacrylophenones and a chromanone from Nama hispidum
and Nama johnstonii, Phytochemistry, 33(4), 936, 1993.
6. Arriaga-Giner, F. J., Wollenweber, E., Schober, I., and Yatskievych, G., Three new benzoic acid
derivatives from the glandular excretion of Eriodyction sessilifolium Hydrophyllaceae. J. Biosci., 43(5-
6), 337, 1988.
7. Liu, Y. L., Ho, D. K., Cassady, J. M., Cook, V. M., and Baird, W. M., Isolation of a potential cancer
chemopreventive agents from Eriodictyon californicum, J.Nat. Prod., 55(3), 357, 1992.
8. Bacon, J. D., Fang, N., and Mabry, T. J., Systematics of Nama (Hydrophyllaceae): flavonoids and
phyletic position of sect. Arachnoidea and sect. Cinerascentia, Plant Syst. Evol., 151, 223, 1986.
9. Bacon, J. D., Hannan, G. L., Fang, N., and Mabry, T. J., Chemosystematics of the Hydrophyllaceae
flavonoids of three species of Eriodyction, Biochem. Syst. Ecol., 14(6), 591, 1986b.
10. Binder, B. F., Bowers, W. S., and Evans, P. H., Insect anti-juvenile hormone and juvenile hormone
activity from plants in the genus Nama, Experientia, 47(2), 199, 1991.
11. Binder, B. F., Trichomes of Nama (Hydrophyllaceae) that produce insect-active compounds, Alosi,
14(1), 35, 1995.
12. Gomez, F., Quijano, L., Calderon, J. S., and Rios, T., Terpenoids isolated from Wigandia kunthii,
Phytochemistry, 19(10), 2202, 1980.
13. Cruden, R. W., Information on chemistry and pollination biology relevant to the systematics of
Nemophila menziesii (Hydrophyllaceae), Madroño, 21(8), 505, 1972.
14. Munz, P. A., Dermatitis produced by Phacelia (Hydrophyllaceae). Science, 76, 194, 1932.
15. Berry, C. Z., Shapiro, S. I., and Dahlen R. F., Dermatitis venenata from Phacelia crenulata, Archs.
Derm. (Chicago), 85, 737, 1962.
16. Mitchell, J. and Rook A., Botanical Dermatology, Greengras Ltd., Vancouver, BC, 1979, 352.
17. Reynolds, G. W. and Rodriguez, E., Geranylhydroquinone: a contact allergen from trichomes of
Phacelia crenulata, Phytochemistry, 18(9), 1567, 1979.
18. Reynolds, G. W. and Rodriguez, E., Dermatotoxic phenolics from glandular trichomes of Phacelia
campanularia and P. pedicellata, Phytochemistry, 25(7), 1617, 1986.
19. Reynolds, G., Epstein, W., Terry, D., and Rodriguez, E., A potent contact allergen of Phacelia
(Hydrophyllaceae), Contact Derm., 6, 272, 1980.
CONTENTS
14.1 Introduction
14.1.1 Botany and Classification
14.1.2 Primula
14.1.2.1 Primula obconica Hance
14.2 Chemistry
14.2.1 Flavonoids and Free Flavonoid Aglycones
14.2.2 Quinones and Phenols
14.2.3 Saponins and Other Triterpenes.
14.3 Clinical Effects
14.3.1 Allergenic Principles
14.3.2 Contact Dermatitis to Primulaceae Plants
14.3.2.1 Primula Dermatitis (Primula obconica Hance)
14.3.2.2 Dermatitis from Other Primulaceae Species
14.3.3 Patch Testing
14.4 References
14.1 INTRODUCTION
The Primulaceae (Primrose family) is a family of perennial or annual herbs, including a number
of popular garden ornamentals, such as primulas and cyclamens. Approximately 1000 species,
distributed among 23 genera, constitute this family of dicotyledons. The family is cosmopolitan in
distribution but with most members found in the north temperate zone.1-5
Many species in this family have medicinal properties and have been used frequently in
herbal medicine. Anagallis arvensis (scarlet pimpernel), a weed of worldwide distribution known
to be poisonous if taken internally, is, for example, used as a direutic or pyretic in Europe, as a
remedy for bites by snakes and mad dogs, and has been shown to possess antiviral properties.6-8
Lysimachia vulgaris, also known as yellow loosestripe, is used in herbal medicine as an astringent
and stypic but has also reputed uses as a febrifuge or fever reducing agent.4,9 Some species of
the Primulaceae are also known for their allergenic properties and especially, Primula obconica
(poison primrose) and a few other primulas are frequent producers of allergic contact dermatitis
(see Section 14.3.2).
Economically, the Primulaceae is mainly of ornamental importance and many species from
different genera are in cultivation; however, Primula and Cyclamen species constitute the major
part of cultivated ornamentals.4,5,10 Many Primula species are cultivated for their attractive flowers
either as house pot plants (e.g., P. · kewensis, P. malacoides, and P. obconica), in rock gardens
14.1.2 PRIMULA
Primula is an important garden genus in terms of the number of varieties grown and the income
generated by the horticultural industry.5,10 Primula is also among the largest and most widespread
of all plant genera.5 According to Richards,5 the genus Primula consists of approximately 425
species that are primarily distributed in the north temperate regions. By far, the greatest concen-
tration of species is found in the great mountain chain of the Himalaya and western China. According
to Richards,5 the genus is systematically divided into 37 sections, of which, 24 sections are endemic
to the Sinohimalaya. In the eastern Sinohimalaya, between 90 and 100°E and 25 to 30°N, encom-
passing Sichuan, Yunnan, Upper Burma, Assam, and southeast Tibet, about half of all Primula
species (225 species) are to be found. In the adjacent central Himalaya, an additional 63 species
are recorded and in the western Himalaya about 29 species are found. All together, temperate Asia
accounts for approximately 80 percent of all Primula species. In contrast, Europe only has 33
species, classified into 4 sections, and North America has 20 species classified into 5 sections.
Primula is not present in Australia and in southern and central Africa and only one species has
been found in South America.
Primulas are herbaceous perennials or, in a few cases, biennials or annuals. Many species
produce farinose (meal) on leaves, stems, and/or inflorescences. Typically they have a basal rosette
of leaves, with or without petioles. The lamina may be simple or lobed and the margins entire or
toothed. Flowers are solitary, in umbells, or in superimposed whorls. Flower colors range from
white through cream to yellow and orange, from pale pink to deep red, and from purple, violet-
purple, to blue. The flowers have a tubular, funnel-, or bell-shaped, five-parted, persistent calyx
and a corolla with a slender cylindrical- or funnel-shaped tube and five spreading or, less often,
more or less erect lobes (petals) often emarginated at the apex. There are five stamens with short
filaments and one style. The relative lengths of stamens and style differ in individual plants
(heterostylous). The fruits are capsules.
Many species and horticultural varieties of Primula are today grown in gardens worldwide and
some are very popular as pot plants. Primulas were already popular in Europe in the eighteenth
and nineteenth centuries. The cultivated primulas at that time were complex hybrids of European
species such as P. vulgaris Hudson (common primrose), P. veris L. (cowslip), and P. elatior (L.)
Hill (oxlip), today known as P. · polyanthus or hybrids of the common primrose and the bear’s
ear (P. auricula L.) known as the garden Auriculas.5,10 At the same time, the Chinese and Japanese
cultivated their own horticultural varieties of P. sinensis Sabine ex Lindley (syn. P. praenitens Ker-
Gawl.) and P. sieboldii Morren. However, it was the European who introduced and started to breed
the Asian species P. obconica Hance and P. malacoides Franchet (fairy primrose) that turned out
to be very popular twentieth century house plants. Unfortunately, these are also among the most
allergenic ones and, especially, P. obconica has been and still is responsible for numbers of severe
cases of allergic contact dermatitis (see Section 14.3.2.1).
Primula obconica Hance was introduced by Charles Maries from Ichang, west Hubei in 1879 to
Messrs. Veitch (London) and, in 1880, the first description of the plant was published by Hance
who gave it the present name.11,12
Primula obconica is a very popular plant for heated glasshouses, and is by far the most
successful primula as a house plant, primarily because it is remarkably tolerant to modern central
heating; that is not the case for most primulas.5,10 P. obconica is relatively short-lived, needing
replacement from seeds. However, if the plants are repotted after flowering they may last for several
years, although they rarely flower well in subsequent years. In tropical and Mediterranean climates,
P. obconica is sometimes used for decorative bedding schemes, but it is less popular than P.
malacoides or P. sinensis because the latter species are faster regarding the development of flowers,
for example. P. obconica is also very successful in window boxes and hanging baskets.5,10
There exist several horticultural varieties of P. obconica. The varieties identified as P. obconica
Grandiflora-Group and P. obconica Gigantea-Group (Figure 14.1) have larger flowers in clearer
and more diverse colors than the naturally occurring species. P. obconica Grandiflora is a direct
desendant of the species P. obconica, whereas P. obconica Gigantea is a hybrid between P. obconica
and the nonallergenic P. megaseifolia Boiss. & Bal.10,12 The first horticultural varieties of P. obconica
Grandiflora and P. obconica Gigantea that were bred in the beginning of the twentieth century were
very allergenic. Since then there have been many attempts to breed new nonallergenic P. obconica
varieties12-15 (see also Section 14.3.2.1). In 1990, new strains were introduced with the names
Freedom and Beauty, and claimed to lack the allergen primin5 and, more recently, a new P. obconica
strain named Libre was introduced to the market and should also be nonallergenic.15
Primula obconica is widespread in the Chinese provinces of Yunnan and Sichuan, and occa-
sionally found in the provinces of Hubei, Kweichow, Kwangtung, and southeast Tibet. The species
occurs on limestone, sandstone, and clay-slate up to 3200 m. P. obconica is very variable in size,
leaf-shape, hairiness, flower color, and form. Furthermore, it is difficult to delimit the species
because P. obconica tends to form a morphological continuum with several other species, for
example, P. barbicalyx Wright, P. sinolisteri Balf.f., and P. parva Balf.f.5 Owing to the variability
of P. obconica, at least three varieties within P. obconica have been recognized with, perhaps, more
species being included in P. obconica.5 However, the cultivars of P. obconica are invariable and
according to Richards5 many of the existing horticultural variants were perhaps among the seedlings
of Charles Maries’ initial introduction of the plant.
14.2 CHEMISTRY
From the many phytochemical investigations carried out so far on species belonging to Primulaceae,
it appears that triterpenoids, flavonoids, and other phenolics are widely distributed in the family.
Mono-, di-, and oligosaccharides that primarily function as storage products, are accumulated both
in roots and aerial parts of most species in the Primulaceae.16-20 For example, the sugars are
hamamelose, hamamelitol, and clusianose and are widely distributed in the genera Primula, And-
rosace, and Soldanella.17-20 Alkaloids so far have not been isolated from Primulaceae. This is not
surprising, considering the fact that alkaloids only seem to be sporadically present in related families
such as Plumbaginaceae and Myrsinaceae.21
Corideae
Coris hispanica Lange 25(G), 27(G) 47
C. monspeliensis L. 24, 25(G), 27(G) 47, 158
Cyclamineae
Cyclamen africanum Boiss. & Reut.b 25(G), 27(G), 38 46
C. balearicum Willk. 27(G) 46
C. cilicium Boiss. & Heldr. 38 46
C. coum Mill. 27(G), 38 46
C. cyprium Ky. 38 46
C. graecum Link 25(G), 27(G), 29(G), 38 46, 47
C. libanoticum Hildebr. 27(G), 38 46
C. neapolitanum Ten. (= C. hederifolium Aiton)c 25(G), 27(G), 38 46
C. persicum Mill. 25(G), 27(G), 29(G), 37, 38 46, 159
C. pseudibericum Hildebr. 27(G), 38 46
C. purpurascens Mill. (syn. C. europaeum L.)c 25(G), 27(G), 38 46
C. repandum Sibth. & Smith 27(G), 38 46
C. rohlfsianum Asch. 38 46
Lysimachieae
Anagallis arvensis L. 25(A,G), 27(A,G), 33, 38 47, 159, 160
A. arvensis L. f. coerulea 23(A,G), 27(G), 38 161
A. linifolia L. (syn. A. monelli (L.))c 25(G), 27(G) 47
A. rubricaulis Bojer ex Duby 27(G) 162
Asterolinum stellatum Hoffm. & Link (syn. A. linum- 25(G), 27(G) 47
stellatum (L.) Duby)c
Centunculus minimus L. (syn. Anagallis minima (L.) 25(G), 27(G) 47
Krause)c
Glaux maritima L. 27(G) 47
Lysimachia atropurpurea L.b 25(G), 27(G) 47
L. christinae Hance var. typica Knuth 24, 25(G), 28(G) 163
L. cuspidata Blume 27(G) 47
L. ephemera L. 25(G), 27(G), 29(G), 35, 37 159
L. fortunei Maxim. 25(G)–27(G) 164
L. japonica Thunb. 25(A,G), 27(A,G) 63, 64
L. clethroides Duby 25(G), 27(G) 63
L. nummularia L. 25(G), 27(G)–29(G), 34, 35, 37 47, 165, 166
L. mauritiana Lam. 25(G), 27(G) 167
L. punctata L. 27(G), 29(G), 35, 37 159, 168
L. stricta Soland. 25(G), 27(G) 47
L. thyrsiflora L. (syn. Naumburgia thyrsiflora (L.) 25(G), 27(G) 47
Reichenb.)c
L. vulgaris L. 25(G), 27(G), 29(G), 35, 37 47, 159, 169-
171
L. vulgaris L. var. davurica (Ledeb.) R. Knuth 25(G)–28(G) 171
Steironema ciliatum L. (Rafin.) 25(G), 27(G), 29(G), 35, 37d 47, 159
S. heterophyllum Rafin. 27(G)d 47
S. radicans A. Gray 25(G), 27(G) 47
Trientalis americana Pursl. 25(G), 27(G) 47
T. europaea L. 25(G), 27(G) 47
Primuleae
Androsace lactea L. 25(G), 27(G) 47
A. lanuginosa Wall. 27(G), 35 47
A. obtusifolia All. 25(G), 27(G) 47
A. sarmentosa Wall. 25(G), 27(G), 35 47
A. sempervivoides Jacquem. 27(G), 35 47
A. villosa L. 25(G), 27(G) 47
Cortusa matthioli L. 1, 15(G), 25(G), 27(G), 38 16, 23, 47
Dionysia archibaldii Wendelbob 40 27
D. aretioides (Lehm.) Boiss. 1, 15(G), 25(G), 27(G), 32(G) 27, 47
D. bornmuelleri (Pax) Clay 1, 15(G), 25(G), 27(G), 32(G) 27
D. bryoides BoisS. 15(G), 40 27, 47
D. curviflora Bunge 40 27
D. diapensiifolia Boiss. 1, 15(G), 25(G), 27(G) 16, 23, 47
D. microphylla Wendelbo 1, 15(G), 25(G), 27(G), 40 27
D. paradoxa Wendelbo 15(G), 25(G), 27(G), 32(G) 27
D. revoluta Boiss. 1, 15(G), 25(G), 27(G) 16, 23, 47
D. tapetodes Bunge 1 16, 23
D. teucrioides Davis & Wendelbo 1, 15(G), 27(G) 27
Dodecatheon meadia L. 15(G), 25(G), 27(G), 38 47
D. cusickii Greene 15(G), 25(G), 27(G) 47
D. clevelandi Greene 15(G), 27(G) 47
Douglasia vitaliana B. & H. 27(G), 32(G) 47
Hottonia palustris L. 25(G), 27(G), 35 47, 159
Primula algida Adamsb 1 16, 23
P. alpicola (Smith) Stapf 1, 2, 5, 6, 10, 11, 15(A,G), 25(G), 30, 47
27(G), 30(G), 32(G), 40
P. americana Rydb. (= P. incana M. E. Jones)c 1 16, 23
P. anisodora Balf.f. & Forrest (= P. wilsonii Dunn)c 25(G), 27(G), 40 47
P. aurantiaca Smith & Forrest 15(G), 27(G), 35 47
P. aureata Fletcher 1, 15(G), 27(G) 27
P. auricula L. 1, 2, 5, 6, 10, 15(A,G), 25(G), 29(G), 16, 23–25,
38 30, 47
P. beesiana Forreste 1, 2, 5, 6, 9, 12, 14, 15(A,G), 25(G), 16, 24, 25, 30,
27(G), 38, 40 34, 35, 47
P. boothii Craib 15(G), 25(G), 40 47
P. boveana Decne. ex Duby (syn. P. involucrata Sweet)c 1, 15(G), 25(G), 27(G) 27
P. bulleyana Forreste 1–3, 5, 6, 9, 12, 14, 15(A,G), 18, 16, 24, 25, 30,
27(G), 38, 40 33–35, 47
P. burmanica Balf.f. & Ward 1, 15(G), 25(G), 27(G), 38, 40 16, 24, 25, 47
P. capitata Hook.f. (syn. P. mooreana Balf.f. & Smith)c 1–3, 5, 6, 15(A,G), 25(G), 27(G), 29, 16, 23–25,
40 30, 33, 47
P. capitellata Boiss. 1 16, 23
P. cawdoriana Ward 15(G), 25(G), 27(G), 40 47
P. chungensis Balf.f. & Ward 1, 15(G), 27(G), 35 16, 24, 25, 47
P. chionantha Balf.f. & Forrestf 10, 15(G), 25(G), 27(G) 27, 47
P. clarkei Watt 15(G), 25(G), 39 47
P. cockburniana Hemsl. (syn. P. operculata R. Knuth)c 15(G), 27(G), 35 47
genus.47
c Synonyms are given in parentheses and are in accordance with those recorded by Richards 5 and/or in Flora Europaea.212
e Primula beesiana and P. bulleyana are similar in structure and are sometimes treated as one species. Richards 5 classify
them as subspecies.
f Richards5 treats Primula chionantha and P. sinopurpurea more or less as one species.
g The authority for the species investigated is not given in the reference(s).
luteolin (23). These compounds have so far not been isolated from other species within Primulaceae,
although the aglycones have been isolated from Primula veris L. (Table 14.1).
The tissue flavonoids in the tribe Cyclamineae are based on the well-known flavonols
kaempferol (25) and quercetin (27) that also seem to be the case for the tribes Samoleae and
Corideae, although a di-C-glucoflavone (24, vicenin-2) has been isolated from the latter tribe. C-
Glycosylflavonoids are widely distributed in the plant kingdom43 but have only been detected in
Coris monspeliensis L., Lysimachia christinae Hance var. typica Knuth (24), and two Steironema
species (structures of C-glucoflavones not determined) within Primulaceae (Table 14.1). The fla-
vonol glycosides in the tribe Lysimachieae, in addition to kaempferol and quercetin, also are based
on myricetin (29) and sometimes also on isorhamnetin (26) and syringetin (28) (Table 14.1).
Members of Cyclamineae, Corideae, Lysimachieae, and Samoleae are, in general, not characterized
by farinose coating and they seem not to produce low oxygenated flavones (Table 14.1).
The genus Primula also shows a rich variation in anthocyanins (flower pigments). The antho-
cyanin hirsutin (hirsutidin (40) 3,5-diglucoside) is the most common anthocyanin found in Primula
and it also occur regularly in Dionysia (Table 14.1). Anthocyanins based on the anthocyanidins
cyanidin (35), delphinidin (37), and malvidin (38) are also common pigments in Primula and
especially cyanidin and delphinidin appear to be widely distributed in the subtribe Primuleae. More
rare in Primuleae are the anthocyanins based on pelargonidin (33), peonidin (34), petunidin (36),
and rosinidin (39) (Table 14.1 and Figure 14.2). The tribe Cyclamineae is characterized by antho-
cyanins exclusively based on malvidin, whereas in the tribe Lysimachieae, pigments based on
malvidin, cyanidin, and delphinidin are regularly found (Table 14.1). From the tribe Samoleae,
anthocyanins based on cyanidin and delphinidin have been isolated, whereas the small tribe
Corideae so far has not been investigated for anthocyanins. The anthocyanins found in Primulaceae
are widely distributed in the plant kingdom except for those based on rosinidin.44,45
Leucoanthocyanins, which are widely distributed in nature, also are shown to be present
throughout the Primulaceae, although the genus Soldanella do not seem to contain these compounds
(Table 14.1). Nearly all leucoanthocyanins present in Primulaceae yield cyanidin or delphinidin
upon acid treatment, indicating that the majority of leucoanthocyanins are based on the flavan-3,4-
diols leucocyanidin and leucodelphinidin.46,47
did not identify the glycoside part. However, previous investigations of the roots of P. vulgaris have
shown that 54 and 55 are present as the glycosides primulaverin and primverin, respectively, both
having the disaccharide primeverose (6-O-b-D-xylopyranosyl-D-glucose) linked in the 2-position.49
Primulaverin and primverin have also been isolated from P. elatior (L.) Hill, P. X kewensis Hort.,
and P. veris L. (Table 14.2). A further glycoside has been isolated from the roots of P. auricula L.
that has been shown to consist of paeonol (57) and primeverose.50 The phenolic glycosides found
in the roots of Primula species have so far only been found in this genus, with the exception of
the aglycone paeonol, that has, for example, also been isolated from Bathya meridionalis (Rubi-
aceae)51 and Cyanchum paniculatum (Asclepiadaceae).52
Many Primula species produce farinose coating on leaves and stems and in the majority of
cases this coating constitutes low oxygenated flavones, as mentioned in Section 14.2.1. However,
P. obconica Hance lacks meal. Instead, its glandular hairs produce simple phenols (43–49) and
quinones (41, 42) of which primin (41) and miconidin (43) are the major constituents (Figure
14.3).53-55 Primin, the major allergen in P. obconica, has also been isolated from the aerial parts of
P. elatior (L.) Hill subsp. elatior and preliminary investigations of several species of the Primulaceae
family by TLC and Craven’s test have indicated the presence of primin in 15 Primula species and
in Androsace hirtella Dufour, Dionysia aretiodes (Lehm.) Boiss., and Glaux maritima L. (Table
14.2).56 Primin has also been isolated from the black rock seaurchin, Paracentrotus lividus Lam.,57
and from Miconia species (Melastomaceae) that also contain miconidin.58-60 Other quinoid com-
pounds of unknown structures have been detected, furthermore, in 48 other species of the Primu-
laceae by using TLC and Craven’s test.56 The majority of these compounds are most likely flavonoid
hydroquinones such as primetin (10) because they occur regularly in Primulaceae (see Section
14.2.1 and Table 14.1) and are positive in Craven’s test.61 From Lysimachia japonica Thunb.,
salicylic acid (52) has been isolated together with two cytotoxic resorcinol derivatives (50, 51).62-64
Cytotoxic activity also has been demonstrated for primin and miconidin.58-60
glycosides that yield on hydrolysis, one or more sugar units and sugarfree aglycones commonly
referred to as sapogenins. Triterpenoid saponins as, for example, those found in Primulaceae are
widely distributed in the plant kingdom and constitute the majority of the naturally occurring
saponins.65-67 Most of these triterpenoid saponins differ only in the numbers and the type of the
carbohydrate moiety linked to the particular sapogenin. In the majority of chemical investigations
of the saponins from the Primulaceae they have been hydrolysed to sugars and the respective
aglycones and identified separately. The hydrolysis of saponins is normally achieved with 2–6 N
HCl, although other methods have been used such as enzymatic hydrolysis.65-67 However, as the
acid hydrolysis of saponins often initiate rearrangements or chemical breakdown of the sapogenins,
Cyclamineae
Cyclamen africanum Boiss. & Reut. 59(G),b 72(G) 188
C. balearicum Willk. 59(G),b 72(G) 188
C. cilicicum Boiss. & Held. 59(G),b 72(G) 188
C. coum Mill. 72(G), 74(G), 81(G) 189
C. coum subsp. coum 59(G)b, 72(G) 188
C. creticum Hildebr. 59(G),b 72(G) 188
C. cyprium Schott & Kotschy 59(G),b 72(G) 188
C. graecum Link 59(G),b 72(G) 188, 190
C. mirabile Hildebr. 59(G), 72(G), 74(G), 78(G) 188, 191
C. neapolitanum Ten.c 59(G),b 72(G) 188, 190
C. persicum Mill. 59(G),b 72(G) 188
C. pseudibericum Hildebr. 59(G),b 72(G) 188
C. purpurascens Mill.c 59(G),b 66(G),d 72(G) 188, 190, 192–194
C. repandum Sibth. & Smith 59(G),b 72(G) 188
C. repandum var. rhodense Meikle 59(G),b 72(G) 188
Lysimachieae
Anagallis arvensis L. 60(G)e 63(G),e 64,e 67(G),e 68(A, G),e 6, 8, 68-76, 160
69(G),e 70,e 71(G),e 86e 95,e
Lysimachia clethroides Duby 59(G),b 65(G),d 79(G)d 195, 196
L. japonica Thunb. 59(G),f 64, 196
L. mauritiana Lam. 61(G), 79(G)d 195, 196
L. sikokiana (L.) Miquel 59(G)e 197
Primuleae
Androsace rotundifolia var. hazaricag 59(G)b,e 198
Androsace saxifragifoliag 72(G), 73(G),e,f 199-201
Primula denticulata J. E. Smith 72(G)e 202, 203
P. elatior (L.) Hill 59(G), 77(G)d 204-206
P. elatior subsp. meyeri (Rupr.) Valentine & Lamond 59(G) 207
P. japonica A. Gray 59(G),b 79(G) 195, 196
P. rosea Roylec 82(G),e 83e 85e 81, 82
P. sieboldii Morren 59(G), 65(G)d 195, 196, 208
P. macrophylla D. Don. 75(G)e 209
P. veris L.c 59(G),b 60(G), 61(G),d 80(G) 16, 195, 210, 211
P. veris subsp. macrocalyx (Bunge) Ludi 60(G), 61(G), 68(G) 207
P. vulgaris Hudsonc 59(G)b 16, 210
a Compounds have been isolated from roots unless otherwise noted and the letter G in parentheses signifies occurrence
as a glycoside (saponin). Sapogenins obtained after acid hydrolysis of saponins and that are known to be artifacts are
not included in Table 14.3, unless it is uncertain whether they are artifacts or not.
b Primulagenin A (76) was isolated after acid hydrolysis of saponins and is likely to be an artifact. The original sapogenin
d Sapogenin obtained after acid hydrolysis and/or periodate oxidation of saponins and could be an artifact.
g No authority for the species investigated has been given in the reference(s).
with the theory that phenolic contact allergens require oxidation to a quinone that can then bind
covalently to a protein nucleophile generating an antigenic complex (Figure 14.6).94,95 It is, therefore,
very likely that miconidin that easily can be oxidized to primin in vivo is allergenic, and, if so,
cross-reactivity between miconidin and primin will be expected. Furthermore, if miconidin has
sensitizing properties, it may be the second allergen of Cairns.
The reactivity of primin towards proteins lies in the electrophilic properties of the quinoid
structure (Figure 14.6). Besides primin, many other naturally occurring benzo- and naphthoquinones
have shown to be strong sensitizers, in accordance with their reactivity toward skin proteins.95
Structure-activity relationships in allergic contact dermatitis with different derivatives of primin
have shown that the sensitizing capacity of naturally occurring quinones depends not only on the
quinoid structure but also on the position, configuration, and the length of their side chains.96-100
For example, increases in the sensitizing potency of primin analogues with increasing length of
the alkyl side chain from C1 to C10 reaches a maximum at 11 and 12 C-atoms. On further elongation,
the sensitizing potency decreases beyond C13, reaching sensitizing values that finally are comparable
with those obtained from primin analogues with 1 to 3 C-atoms.99,100 Similar structure-activity
relationships have been found with ortho-hydroquinones (catechols) chemically related to urushiol,
the active principle of, for example, poison ivy (Toxicodendron radicans, Anacadiaceae)101-104 and
prenylated phenols from the Phacelia species,89-93 although hydroquinones first have to be oxidized
to the corresponding quinones in order to gain sensitizing activity. Other studies with primin and
related quinones have shown that optimal sensitizing reactivity occur when the alkyl chain in the
6-position is opposite to the methoxy group in the 2-position (Figure 14.3).96,97 Substitution in the
5-position clearly diminishes the reactivity that indicates that the position of the side chains in the
quinones are of importance for sensitizing activity.96,97 Also, the number of substituents in the ring
has a great influence on the sensitizing activity of quinones owing to steric hindrance and because
the number of active sites are reduced with increasing numbers of substituents.105 Finally, it has
been shown that quinones with a cyclic configurated side chain have a lower sensitizing activity
than quinones having an alkyl side chain. For example, primin has a much stronger sensitizing
effect in guinea pigs than the allergenic dalbergiones [e.g., R-5,6-dimethoxy-2-(1¢-phenylallyl)-1,4-
benzoquinone (equal to R-3,4-dimethoxydalbergione)] that are quinones with almost the same
quinoid structure as primin but with side chains of 9 to 10 carbon atoms in cyclic configuration.98
The dihydroxyflavone primetin (10), found in several Primula species (Table 14.1) has been
shown to possess strong contact sensitizing properties as demonstrated in some experiments with
Primula dermatitis is caused nearly always by Primula obconica, although case reports of dermatitis
or skin irritating effects from other Primula have been reported (Table 14.4 and Section 14.3.2.2).
After the introduction of P. obconica into England from China in 1880, the plant rapidly became
established as a popular ornamental plant throughout Europe and the United States. Very soon after
case reports of dermatitis appeared and it became clear that P. obconica was a highly sensitizing
plant.9,108-119 The sensitizing properties of P. obconica are probably due to the accessibility of the
allergen primin on the surface of the plant.56,83,88,97,120,121 The allergen is formed in minute glandular
hairs consisting of three to five cells. The allergen accumulates between the cuticula and the cell
membrane of the outmost cell. When the cuticula burst, the concentrated allergen accumulates as
irregular resinous drops on the top and sides of the hair. Primula obconica has, similar to many
other Primula species, visible long hairs (1–3 mm) (see also Sections 14.1.2 and 14.1.2.1). However,
these hairs do not contain primin, and an impression of hairiness does not give any indication of
the site of the allergen.56,83,88,97,121 For example, the petiole appears (leaf stem) very hairy but contains
less primin than the other organs. The highest concentrations of primin is normally found on the
calyx and decreases in the following order: pedicel (flower stalk), carpel, leaves, petiole, and
inflorescent stem.56,83,88,97,121
The amount of allergen formed in P. obconica varies considerably, depending on the season,
photoperiod, cultivation practice, and the horticultural variety.9,97,121,122 The primin content is, for
Anagallis arvensis L. Scarlet pimpernel Irritant properties; leaves and 9, 56, 88, 148
flowers can cause dermatitis
Cortusa matthioli L. Alpine bells Frequently produces irritant 9, 56, 149, 150
patch test reactions and can
cause allergic contact
dermatitis
Cyclamen persicum Miller Sowbread Dermatitis described 9, 56, 88
Lysimachia nummularia L. Creeping Jenny or Dermatitis described 56, 88
Moneywort
Primula auricula L. Bear’s-ear Contact dermatitis described 88
P. cortusoides L. Mild skin irritant effect and can 9, 83, 123
produce irritant patch test
reactions
P. denticulata J. E. Smith Drumstick primula Dermatitis observed 56
P. elatior (L.) Hill Oxlip Can cause allergic contact 56, 145
subsp. elatior dermatitis
P. farinosa L. Bird’s-eye primrose Dermatitis described 9, 56, 106
P. japonica A. Gray Japanese primrose May cause dermatitis 56, 88
P. malacoides Franchet Fairy primrose Can produce irritant patch test 9, 83, 123, 126, 137
reactions and cause allergic
contact dermatitis
P. mistassinica Michaux Causes allergic contact 56, 61, 106
dermatitis; allergen identified
as primitin (10)
P. obconica Hance Poison primrose Causes frequently allergic e.g. 9, 56, 108–121,
(syn. P. poculiformis Hook.f) contact dermatitis; allergen 123–130, 137–148,
identified as primin (41) and 151–154
probably more are present
P. praenitens Ker-Gawl. Chinese primrose Potential irritant by patch test 9, 56, 123, 142–144
(= P. sinensis Sabine ex Lindley) and can cause allergic contact
dermatitis
P. sieboldii Morren Skin irritant properties 9, 83
P. veris L. Cowslip Allergic contact dermatitis 9, 146
(syn. P. officinalis (L.) Hill) described
P. veris subsp. columnae (Ten.) Dermatitis described 9, 88
Ludi (syn. P. suaveolens Bertol.)
P. veris subsp. veris Dermatitis described 56, 147
example, highest during a warm summer and lowest during the winter when a plant may give
negative patch test reactions in a primin sensitive person. Because of the commercial importance,
many new varieties has been produced by selection, hybridization, and mutations.5,10,13-15 Most of
the new varieties of P. obconica have the same density of glandular hairs where the allergen is
formed. However, some varieties produces less allergen than others and there have also been reports
of some P. obconica varieties that do not produces primin (see Section 14.1.2.1).13-15 However,
Fregert and Hjorth120 have been able to detect primin in P. obconica Reizfrei that should be free
of primin. It is, therefore, advisable to test so-called primin-free cultivars carefully before intro-
duction to the market because they still may produce small amounts of primin. This may be the
are both false negative and false positive irritant reactions (see Section 14.3.3). However, there
might be more than one allergen in P. obconica and, therefore, there is also a minimal risk for a
false negative reaction when using synthetic primin for patch testing.53,56,87,134 Dooms-Goossens et
al.134 have, for example, described two cases in which primula dermatitis would have been missed
if they only had relied on patch testing with synthetic primin instead of plant material or extracts.
Several investigations have shown that the frequency of positive patch tests with primula leaf or
primula extract in consecutively patch tested patients are higher (3.4 to 8.8 percent positive patch
tests)122,124 than those patch tested with 0.01 percent synthetic primin (0.3 to 1.8 percent positive
patch tests).127,129,134 These differences may be owing to a larger number of false positive irritant
reactions in the patch tests performed with extracts or plant material when compared to those
performed with primin (see Section 14.3.3). Furthermore, patch testing with synthetic primin in a
low concentration perhaps only gives positive results if the patient has developed an allergy to a
certain high level. So far, only one case of photoallergic contact dermatitis to P. obconica has been
described where only patch tests with synthetic primin in the presence of UV-A light gave a positive
reaction in a person with severe primula dermatitis.135 Although P. obconica is very popular in
Spain and Portugal, for example, positive patch tests to primin are rare.135 It is, therefore, possible
that many cases of primula dermatitis are overlooked, simply because they present with primula
photosensitivity. Therefore, one might suggest photopatch tests in patients with suspected primula
dermatitis who are negative in standard patch tests.
Primula dermatitis is seldom found among males. This is in accord with several major patch tests
studies with primin or P. obconica extracts showing that among patch test positive patients between
85–95 percent were females.9,97,122,124,126,129 Florists and nursery persons are commonly sensitized, but
the majority of cases of primula dermatitis are found among housewives. This also explains the few
number of males with primula allergy because it is still uncommon in most countries that males have
household duties. Primula dermatitis is not very common under the age of 30 but occur regularly
among middle age persons.9,97,124,127,129,131 However, in more recent investigations on the prevalence
of primula sensitivity in Northern Europe, there seems to have been an increase in the number of
sensitized persons in the group between 55–80 years and a decline in the number of sensitized persons
in the groups under the age of 40 when compared to previous investigations.127,129 This tendency could
be due to the fact that more women are working outside the home than before and, pressumably, they
have much less time for household duties such as taking care of flowers compared to older women.
The presence of primin in other primulas than P. obconica may explain the few reports of dermatitis
and skin irritant properties of species such as P. praenitens Ker-Gawl. (equal to P. sinensis Sabine
ex Lindley), P. denticulata Smith, P. elatior (L.) Hill subsp. elatior, P. malacoides Franchet, P.
veris L., and P. veris subsp. veris (see Tables 14.2 and 14.4). The first reports on the skin irritating
properties of P. praenitens appeared around 1900.142,143 Later, Fregert and Hjorth144 showed that
the plant can produce irritant patch test reactions and is a potential irritant by patch test.144 P.
praenitens9,123 has also been shown to cause allergic contact dermatitis but only very rarely, and
the same goes for P. elatior subsp. elatior,56,145 P. veris,146 and P. veris subsp. veris.56,147 Primula
malacoides9,123 can produce irritant patch test reactions, but it has never been proven that the plant
can cause allergic contact dermatitis, although Richards5 claims that P. malacoides and P. praenitens
are more allergenic than P. obconica.
Contact dermatitis from Primula mistassinica Michaux where reported by Sharpe,106 who
described four cases of contact dermatitis on the hands in farm workers (milkers). The dermatitis
was attributed to handling the udders of cows that had grassed among the plants and, thereby, took
14.4 REFERENCES
1. Pax, F., Primulaceae, in Die natürlichen Pflanzenfamilien, Engler, A. and Prantl, K., Eds., Verlag von
Wilhelm Engelmann, Leipzig, 1891, 98.
2. Pax, F. and Knuth, R., Primulaceae, in Das Pflanzenreich, Engler, A., Ed., Verlag von Wilhelm
Engelmann, Leipzig, 1905, 1.
3. Melchior, H., in A. Engler’s Syllabus der Pflanzenfamilien, Borntraeger, Berlin-Nikolassee, 1964, 391.
4. Heywood, V. H., Flowering Plants of the World, Oxford University Press, London, 1978, 134.
5. Richards, J., Primula, B.T Batsford, Ltd., London, 1993.
6. Amoros, M. and Girre, R. L., Structure of two antiviral triterpene saponins from Anagallis arvensis,
Phytochemistry, 26, 787, 1987.
7. Amoros, M., Fauconnier, B., and Girre, R.-L., Effect of saponins from Anagallis arvensis on exper-
imental herpes simplex keratitis in rabbits, Planta Med., 54, 128, 1988.
8. Shoji, N., Umeyama, A., Yoshikawa, K., and Arihara, S., Triterpenoid glycosides from Anagallis
arvensis, Phytochemistry, 37, 1397, 1994.
9. Mitchell, J. and Rook, A., Botanical Dermatology—Plants and Plant Products Injurious to the Skin,
Greengrass, Ltd., Vancouver, BC, 1979, 544.
10. Everett, T. H., The New York Botanical Garden Illustrated Encyclopedia of Horticulture, Vol. 8,
Garland Publishing, Inc., New York, 1981, 2788.
11. Hance, H. F., Stirpium duranum novarum e Primulacearum familia characteres, J. Bot., 18, 234, 1880.
12. Maurer, E. and Storck, A., Untersuchungen zur Züchtung einer giftfreien Primel vom “Obconica”-
Typus, Gartenbauwissenschaft, 10, 1, 1935.
13. Horn, W. and Eltorky, M. G. M., Vererbung von Blütenfarbe und Primin bei Primula obconica, Tag.-
Ber., Akad. Landwirtsch.-Wiss. DDR, Berlin, 281, 97, 1989.
14. Heyting, J. and Toxopeus, S. J., Breeding primin-free Primula obconica, Netherlands J. Agric. Sci.,
37, 371, 1989.
15. Engasser, P. G., Primin-free Primula obconica seeds are available, Am. J. Contact Derm., 6, 252, 1995.
16. Hegnauer, R., Chemotaxonomie der Pflanzen. Eine Übersicht über die Verbreitung und die system-
atische Bedeutung der Pflanzenstoffe, Band 5, Birkhäuser Verlag, Basel, 1969, 387.
17. Hegnauer, R., Chemotaxonomie der Pflanzen. Eine Übersicht über die Verbreitung und die system-
atische Bedeutung der Pflanzenstoffe, Band 9, Birkhäuser Verlag, Basel, 1990, 287.
18. Sellmair, J., Beck, E., and Kandler, O., Zur Physiologie der Clusianose, Z. Pflanzenphysiol., 61, 338,
1969.
19. Sellmair, J. and Kandler, O., Zur Physiologie von Hamamelose und Hamamelit in Primula clusiana
Tausch, Z. Pflanzenphysiol., 63, 65, 1970.
20. Sellmair, J., Beck, E., Kandler, O., and Kress, A., Hamamelose and its derivatives as chemotaxonomic
markers in the genus Primula, Phytochemistry, 16, 1201, 1977.
CONTENTS
15.1 Introduction
15.2 Botany and Classification
15.3 Genera of the Urticaceae of Biological Concern
15.3.1 Parietaria
15.3.1.1 Pollen of Parietaria
15.3.2 Urtica
15.3.2.1 Stinging Hairs
15.4 Chemistry of Urticaceae
15.4.1 Active Agents of the Parietaria
15.4.2 Active Compounds of Stinging Hairs
15.5 Clinical Effects
15.5.1 Allergenicity Due to Parietaria
15.5.2 Contact Urticaria to Urtica
15.5.2.1 Other Evaluations of Urtica Extracts
15.6 References
15.1 INTRODUCTION
The Urticaceae, a family of shrubs, lianas, herbs, or trees, has been responsible for many derma-
tologic reactions. The family is composed of approximately 550 species with 49 genera.1,2 Members
of this plant family can be found in temperate to tropical climates. The family is cosmopolitan in
distribution except for the frigid zones.1,2
Components of two of the species from this family have or are being considered for medicinal
purposes. In earlier times, urtication was practiced for the treatment of certain diseases and
consisted of beating the skin with Urtica nettles.1,3,4 Erythema and whealing are the usual response
in skin following contact with Urtica nettles. However, the skin would cease to react under fresh
contact after the third or fourth successive application of nettles. More recently, the roots or
extracts of the roots, that contain the superantigen Urtica dioica agglutinin (UDA), have been
reported to exert a number of pharmacologic activities such as the treatment of benign prostatic
hyperplasia or systemic lupus.5-8 Currently, the superantigen UDA is being used to explore the
mechanism by which T-cell activation occurs in its presence.5,9-11 In addition, allergens from
Parietaria pollen are being considered for specific immunotherapy for the purpose of therapeu-
tically controlling allergic diseases.12-15 However, the majority of the medical reports involve
either the urticaria reactions observed after exposure to Urtica species or allergic reactions to
Parietaria species.
Although the majority of the plants in Urticaceae are weeds, some members of this family are
still used for economic purposes. For example, the stinging nettles (Urtica species) constitute edible
15.3.1 PARIETARIA
Parietaria is a wind pollinated perennial weed. Members of this genus commonly grow in Italy,
Greece, Portugal, Spain, France, United Kingdom, and throughout southeastern and eastern
Europe.18-26 Species of the Parietaria have also been found in the United States27-29 and Australia.21,31
Parietaria has been reported in the United States for 180 years and in northern California in the
last century.26,27,32,33 Parietaria officinalis and P. judaica are the most common species in the
Mediterranean and Europe within the genus Parietaria. Other species are P. lusitanica, P. mauri-
tanica, and P. cretica.34 P. judaica along with P. floridana, and P. pensylvanica are distributed
widely in the United States.26,32,33 These plants are highly productive and anemophilous. The species
are characterized by numerous, grouped, individually small and drab, scentless florets. Typically,
Parietaria will grow wild and abundantly on walls, ruins, roadsides, and ditches. P. judaica is
thermophilic and heliophilic.25 In Europe, P. judaica will grow commonly in coastal Mediterranean
countries such as Spain, Italy, southern France, the former Yugoslavia, Albania, and Greece.18-25
The habitat for P. officinalis is distributed further in Spain, France, northern Italy, Austria, Bulgaria,
the Czech Republic, Romania, and southwestern regions of the former Soviet Union and in more
hilly or mountainous areas (under 1000 m in altitude) than P. judaica.18-25
The pollen of P. judaica, P. officinalis, and P. lusitanica are very similar in size and appearance.26,27
When examined under a microscope, the pollen grains take an expanded spherical appearance
and are about 15 m in diameter (mean diameter 12–16 m).24,26 Factors that influence pollen output
have been described by D’Amato et al.24 These include temperature, humidity, and light intensity.
Size and shape of the pollen also favor wind pollination. Pollen output begins with the propulsion
15.3.2 URTICA
The Urtica species is a cosmopolitan weed and is highly variable in size. These dark green plants
can grow from 30 to 150 cm high. As described in Section 15.2, most of the 50 species are found
in north temperate regions with a few in tropical and south temperate regions.1 The species most
noted for their stinging capabilities are the Urtica chamaedryoides, U. crenulata, U. dioica, U.
echinata, U. ferox, U. gracilis, U. holosericea, U. hyperborea, U. incisa, U. lobulata, U. lyallii, U.
parviflora, U. pilulifera, U. purpurascens, U. stimulans, U. urens, and U. urentissima.1,42-49 The
majority of these species have been reported in the United States. Besides being found in the United
States, the common nettle (U. dioica) and small nettle (U. urens) were introduced into Europe and
can be found in Australia and South Africa.1 There are two other species that can also be found in
Australia: U. holosericea and U. incisa.1 The U. ferox is native to New Zealand and can be found
throughout the North Island and west of the main divide in the South Island.49-51 U. ferox can grow
up to 3 m in height from sea level to 600 m in altitude.49 In India, three species of the Urtica have
been reported to cause stinging: the common nettle (U. dioica), U. hyperborea, and U. parviflora.1,45
The Urtica are usually dioecious and are with nonarticulated and unbranched laticifers. The
leaves are opposite, ovate, more or less cordate at the base, toothed, petioled, and about 3 to 12
cm long.2,52 The inflorescence is spike-like, axillary, up to 10 cm in length, and the perianth of
flowers is greenish in 4 out of 5 segments.2,52 Male flowers have four or five stamens. The Urtica
received their name from the Latin word, “urere,” which means “to sting.” This species contains
stinging hairs on all stems and leaves.2,52 Shaw,16 classified the Urticaceae by the presence or lack
of stinging hairs, and also identified the Urera and Laportea species with stinging hairs. In addition,
several other species of the Urticaceae are also know to contain stinging hairs.1,4,17,46 These are
Cecropia, Dendrocnide, Fleurya, Girardinia, Gyrotaenia, Hesperocnide, Laportea, Nanocnide,
Obetia, Scepocarpus, and Sceptronide.
The structure of the stinging hair has been described by Thurston.53 The syringe-like hairs have
elongated epidermal and subepidermal layer cells. The apical walls are composed of silica bodies.
The silica bodies are more pronounced at the tip of the hair and decrease in concentration toward
the base of the hair. At the base of the stinging hair, the cell wall lacks silica bodies. The tip of
the hair is very hard and brittle. Once the hair touches the skin, the top of the hair breaks and the
liquid contained within the hair is injected into the skin (see Section 15.4.2 for the contents of
the fluid).
found a high degree of homology (94 percent).69,78 Similarly, a comparison between Par o Ib and
Par j Ib found that only 3 of 19 residues were different: 84 percent homology.78 Kahlert et al.70
found a greater concordance between the N-terminus amino acid sequence for one of the isoallergens
of P. officinalis and the sequenced cDNA for Par j I (83 percent) compared with the 50 percent
homology identified by Ayuso et al. The discordance in molecular weight, amino acid homology,
and other parameters have been attributed to differences in plant species, extent of heterogeneity
of the major allergens in Parietaria extracts, and/or the degree of purity of the isoallergen.
The cross-reactivity between the major allergens found in P. judaica and P. officinalis also
extend into other species of Parietaria. Ayuso et al.84 also found that a strong cross-reactivity existed
between the major allergens of P. judaica and P. officinalis with the major allergen of P. mauritanica.
Using a monoclonal antibody-based ELISA for the quantification of Par j I, proteins homologous
to Par j I were identified (Par o I and Par m I) in P. officinalis and P. mauritanica extracts,
respectively. The proteins then were purified by affinity chromatography and crossed-inhibition
experiments demonstrated that Par j I, Par o I, and Par m I competed for the binding of specific
IgE from a P. judaica-sensitive patient serum pool.85
The potential genotoxicity of Urtica dioica has been evaluated in the Salmonella typhimurium
microsomal activation assay (Ames test), in human lmphocytes in the alkaline single cell gel
electrophoresis (COMET assay), and in the somatic mutation and recombination test (SMART) in
Drosophila melanogaster.95,96 In the SMART assay, water extracts of Urtica dioica were prepared
and fed to larvae. Mitotic recombination or somatic gene mutation, deletion, or another mutational
change at one of the gene markers will result in a single or twin spot on wings of affected progeny.
The frequency of spots per wing were determined for the control and treated groups. Based on the
SMART assay, a weak genotoxic effect was observed with a standard tea preparation and with a
concentrated extract.96 In the Ames test, using strains TA98 and TA100, a saline extract and an
aqueous extract of the arial parts of U. dioica did not produce an increased frequency of revertants.95
In addition, a sugar rich, flavonoid rich, and chloroform fraction of the water extract had similar
findings. However, the Urtica extracts and chloroform and flavonoid fractions did produce a dose-
related increase in tail moments in the COMET assay, suggesting that a component or components
of the extracts or fractions can produce DNA damage by strand breakage.95 Some of the components
15.6 REFERENCES
1. Mitchell, J. and Rook, A., Botanical Dermatology of Plants and Plant Products Injurious to the Skin,
Greengrass Ltd., Vancouver, BC, 1979, 544.
2. Watson, L. and Dallwitz, M. J., The Families of Flowering Plants: Descriptions, Illustrations, Iden-
tification, and Information Retrieval, 8th Version, May 1998, URL http://biodiversity.uno.edu/delta/.
3. White, J. C., Dermatitis Venenata: An Account of the Action of External Irritants upon the Skin,
Cupples and Hurd, Boston, 1887.
4. Martinez, M., The Medicinal Plants of Mexico, 5th ed., Andres Botas, Mexico City, 1969.
5. Wagner, H., Willer, F., and Krehner, B., Biologisch aktive Verbindungen aus dem Wasserextrakt von
Urtica dioica, Planta Med., 55, 452, 1989.
6. Musette, P., Galelli, A., Chabre, H., Callard, P., Peumans, W., Truffa-Bachi, P., Kourisky, P., and
Gachelin, G., Urtica dioica agglutunin, a b-specific superantigen, prevents the development of the
systemic lupus eryhtematosus-like pathology of MRL lpr/lpr mice, Eur. J. Immunol., 26, 1707, 1996.
7. Hryb, D. J., Khan, M. S., Romas, N. A., and Rosner, W., The effect of extracts of the roots of the
stinging nettle (Urtica dioica) on the interaction of SHBG with its receptor on human prostatic
membranes, Planta Med., 61, 31, 1995.
8. Peumans, W., De Ley, M., and Broekaert, W., An unusual lectin from stinging netttle (Urtica dioica)
rhisomes, FEBS Lett., 177, 99, 1984.
9. Delcourt, M., Peumans, W. J., Wagner, M., and Truffa-Bachi, P., b-Specific deletion of mature
thymocytes induced by the plant superantigen Urtica dioica agglutinin, Cell. Immunol., 168, 158, 1996.
10. Galelli, A. and Truffa-Bachi, P., Urtica dioica agglutinin, J. Immunol., 151, 1821, 1993.
11. Galelli, A., Delcourt, M., Wagner, M.-C., Peumans, W., and Truffa-Bachi, P., Selective expansion
followed by profound deletion of mature Vb8.3+T cells in vivo after exposure to the superantigenic
lectin Urtica dioica agglutinin, J. Immunol., 154, 2600, 1995.
12. D’Amato, G., Liccardi, G., Russo, M., Saggese, M., and DeAmato, M., Measurement of serum levels
of eosinophil cationic protein to monitor patients with seasonal respiratory allergy induced by Pari-
etaria pollen (treated and untreated with specific immunotherapy), Allergy, 51, 245, 1996.
13. Ortolani, C., Pastorello, E. A., Incorvaia, C., Ispano, M., Farioili, L., Zara, C., Pravettoni, V., and
Zanussi, C., A double-blind, placebo-controlled study of immunotherapy with an alginate-conjugated
extract of Parietaria judaica in patients with Parietaria hay fever, Allergy, 49, 13, 1994.
14. Andri, L., Senna, G. E., Betteli, C., Givanni, S., Andri, G., Falagiani, P., and Lugo, G., Local nasal
immunotherapy in allergic rhinitis to Parietaria, Allergy, 47, 318, 1992.
15. Mistrello, G., Brenna, O., Roncarolo, D., Zanoni, D., Gentili, M., and Falagiani, P., Monomeric
chemically modified allergens: immunologic and physicochemical characterization, Allergy, 51, 8,
1996.
16. Shaw, H. K. A., A Dictionary of the Flowering Plants and Ferns, 8th ed., Cambridge University Press,
Cambridge, 1973.
17. Allen, P. H., Poisonous and injurious plants of Panama, Am. J. Trop. Med., Suppl. 23, 1, 1943.
18. Charpin, J. and Surinyach, R., Atlas of European Allergic Pollens, Sandoz, Paris, 1974.
19. Charpin, J., Davies, R., Nolard, N., Spieksma, F., and Stix, E., Concentration urbaine des spores
dans les pays de la communaute economique europeenne: les Urticacees, Rev. Fr. Allergol., 17, 181,
1977.
20. Clapman, A. R., Tutin, T. G., and Moore, D. M., Flora of the British Isles, 3rd ed., Cambridge
Univesity Press, Cambridge, 1987.
21. D’Amato, G. and Lobefalo, G., Allergenic pollens in the Mediterranean area, J. Allerg. Clin. Immunol.,
83, 116, 1989.
22. D’Amato, G., Loietti, A., Mandrioli, P., Moro, A., Spediacci, C., and Tursi, A., The spectrum of
allergenic pollen in Italy: a computerized method of aerobiological monitoring, Allergy, 43, 258, 1988.
CONTENTS
16.1 Introduction
16.1.1 Taxonomy
16.1.2 Plant Family
16.1.3 Geographical Location
16.1.4 Genera
16.1.5 Species
16.1.6 Common Names
16.2 Chemistry
16.2.1 Family/Species
16.2.2 Chemical Structure of Active Principles
16.3 Biological Activity
16.3.1 Experimental Assays
16.3.2 Toxicological Assays
16.3.3 Clinical Effects
16.4 References
16.1 INTRODUCTION
16.1.1 TAXONOMY
Kingdom—Metaphyta (Plantae)
Phylum—Spermatophyta (Embriophyta Siphonogama)
Subphylum—Angiospermae
Division—Anthophyta
Class—Monocotyledones
Order—Liliales or Liliiflorae
Family—Agavaceae (Amaryllidaceae)
Genera—Agave, Yucca, Hesperaloè, Littaea, and large cacti which tend to be spherical in
shape
16.1.4 GENERA
The Agavaceae family contains 20 genera which includes the following: Agave, Beschorneria,
Cordyline, Dracaena, Furacrea, Hesperaloë, Littaea, Manfreda, Nolina, Phormiun, Polianthes,
Prochnyanthes, Sansevieria, and Yucca. The Agave genera is the largest genera in this family where
about 300 species are cultivated for fiber and fermented drink.1
16.1.5 SPECIES
Of the 670 species found in the Agavaceae family, a review of the literature did not find any current
clinical use of these plants in humans. However, there are some experimental investigations in
laboratory animals using crude extracts from different species of Agave genera.6 Other reports
found the sap of Agave americana as producing an irritant contact dermatitis in humans.7 Also,
some studies have reported hepatotoxicity and photosensitivity reactions in animals that feed on
the aerial parts of the A. lecheguilla and A. americana.8-11 In addition, some Agave species have
been used in traditional medicine as remedies for healing aerobic wound infections.12 Recently, the
effectiveness of these species has been demonstrated in vitro on some species of bacteria and
fungi.12,13 In Figure 16.1, several specimens of A. lecheguilla are observed.
Other species have been used to obtain products with different commercial purposes. For
example, the Mescal brandy, which is a popular alcoholic beverage in Mexico, is distilled from the
fermented mash of the cooked stems of certain wild and cultivated Agave L. species, especially A.
tequilana, and A. Weber, A. pacifica Trel.4
The aqueous extract of A. fourcryoydes (also known as henequen) decreased the cardiac
frequency in mollusks producing an ovicida mollusquicide effect.6
Yucca aloifolia L. is known as sword leaf or Spanish bayonet. Morton reported eye injury
caused by the short black spine at the leaf tip. The needle-sharp leaf tips of this species may
penetrate the skin and in or near bone may excite a reaction that simulates a neoplasm.21
16.2 CHEMISTRY
16.2.1 FAMILY/SPECIES
The Agavaceae family contains steroidal saponins and sapogenins recognized as precursors in the
production of medicinally used steroids.1 In addition, crystals of calcium oxalate have been reported
as part of the chemical composition of Agavaceae. These crystals have been related to irritants and
allergic effects following contact with members of this family.22
Saponins are a glycosides chemical group that produce a diminution of superficial tension in
water forming a considerable production of foam. Sapogenin (aglycone) and carbohydrates are
obtained after the hydrolysis reaction of saponin. The representative steroidal moiety of the sapo-
genins is the smilagenin (Figure 16.2).23
Approximately 200 steroidal saponins from the monocotyledons have been isolated. However,
fewer sapogenins were obtained when these compounds were hydrolyzed because the isolated
aglycone moiety can be the same compound for two or more saponins.23 All parts of the plant
generally contain steroidal saponins and steroidal sapogenins, more specifically hecogenin (C27 H42
O4), tiogenin (C27 H44 O3), and neotiogenin. Other sapogenins that have been isolated are sisalagenin,
gloriogenin, gentrogenin, gitogenin, delta 9-11-hecogenin, diosgenin, smilagenin, sarasapogenin,
and yamogenin.24-26 The content of each sapogenin can differ within the plant (i.e., leaves, stems,
roots) and the stage of growth.5,23,27 Yuccagenin and diosgenin were isolated in A. tubulata and A.
legrelliana.28 Later, a new steroidal sapogenin diol, ruizgenin (Figure 16.3), was isolated from the
leaves of A. lecheguilla29 and chlorogenin from A. cocui.30
Several steroidal sapogenins were isolated from leaves of eight species of cordyline: cannin-
genin, cordylagenin, brisbagenin, and ruscogenin.31 From the dried fermented residues of leaf juices
of A. sisalana, two new steroidal saponins tigogenin derivates, recognized as dongnosides, were
characterized.32
Another chemical group isolated from extract of leaves of different species of Agave correspond
to enzymes with proteolytic activity.33-35
FIGURE 16.4 Hecogenin is a natural steroid isolated from different Agavaceae species.
The dermal manifestations include acute eczematous dermatitis followed by a contact urticaria
reaction when a shampoo derived from A. americana was used on the scalp, forehead, and wrist.14
Other dermal reactions have been observed in gardeners who have occasion to cut any part of the
plant and who have been exposed to the raw sap of A. sisalana and in factory workers exposed to
the sap and the wet fiber in the extraction process.5
In respect to the effects caused by the oral administration of Agave plants found in the literature,
a case of alimentary intoxication was observed after swallowing the juice from chewing the fibers
of cooked stem quiote of A. americana.41 In this patient, the symptomatology, mostly observed in
the abdomen, was treated with surgery.41 However, other outcomes have also been noted in indi-
viduals taking an oral administration of Agave. No adverse reactions were reported in healthy
normal volunteers following the oral administration of a single dose up to 6 g of crude extract of
rhizome from A. lecheguilla amole.42 In other clinical studies, no side effects nor any gastric,
cardiovascular, or respiratory symptoms were reported in patients treated with capsules containing
500 mg of amole every 12 h for 10 days.43 In the same clinical study, the clinical laboratory values
for blood from amole-treated and nonamole-treated patients did not differ significantly. These
observations were realized after 90 days of treatment.43
16.4 REFERENCES
1. Trease, G. E. and Evans, W. C., Tratado de Farmacognosia, Interamericana, México, 1987, chap. 19.
2. Watson, L. and Dallwitz, M. J., The families of flowering plants: descriptions, illustrations, identifi-
cation, and information retrieval, http://biodiversity.uno.edu/delta, 1992.
3. De la Cruz Campa, J. A. and Medina Torres, J. G., La Lechuguilla (Agave lecheguilla), Recursos
Naturales del Semidesierto, Serie: Plantas desérticas y el hombre, D.I.F. Coahuila, Mexico, 1988.
4. Bahre, C. J. and Bradbury, D. E., Manufacture of mescal in Sonora, México, Econ. Bot., 34, 391, 1980.
5. Morton, J. F., Major Medicinal Plants. Botany, Culture and Uses, Charles C. Thomas, Springfield,
IL, 1977, 67.
6. Diaz-Garces, R. and Ferrer López, J. R., Efecto de las dosis letales de plantas de la familia Agavaceae
sobre la actividad cardíaca y la oviposición de Biomphalaria havanensis (Mollusca: Planorbidae),
Rev. Cubana Med. Trop., 48, 6, 1996.
7. McCord, C. P., The occupational toxicity of cultivated flowers, Ind. Med. Surg., 31, 365, 1962.
8. Mathews, F. P., Poisoning in sheep and goats by sucahuiste (Nolina texana) buds and blooms, Bull.
Tex. Agric. Exp. Stn., 585, 1940.
CONTENTS
17.1 Introduction
17.2 Botanical Classification and Distribution
17.2.1 Composition of Algae
17.2.2 Uses of Algae
17.3 Toxicology
17.3.1 Microcystins
17.3.2 Caulerpenyne
17.3.3 Iodine
17.3.4 Pheophorbide A
17.3.5 Phycocyanin
17.3.6 Phenolic Compounds
17.3.7 2-Hydroxyethyl Dimethyl Sulphoxonium Ion
17.3.8 Spirulina fusiforms
17.3.9 Fucoxanthin
17.3.10 Deoxylapachol
17.3.11 Arsenic
17.3.12 Sesquiterpene Lactones
17.3.13 Proteoglycans
17.3.14 Phocamadiene A
17.3.15 Hepoxilin B3
17.3.16 Domoic Acid
17.3.17 Gelidiella acerosa
17.3.18 General Compounds
17.4 Skin Pathology
17.4.1 Swimmer’s Itch
17.4.2 Dogger Bank Itch
17.4.3 Japanese Sargassum Fensholt
17.4.4 Frullania
17.4.5 Biotoxins
17.4.6 Protothecosis
17.5 References
TABLE 17.1
Classification of Algae
Procarioti Cyanophyceae (blue algae)
Eucarioti Rhodophyceae (pink algae) chlorophyll a; phycobilins
Chlorophyceae (green algae) chlorophyll a, b; carotenoids
Prasinophyceae
Charophyceae
Euglenophyceae chlorophyll a, b; carotenoids
Xantophyceae
Baciophyceae (diatomee)
Chrysophyceae (brown algae) chlorophyll a, c; fucoxanthin
Phaephyceae (brown algae) chlorophyll a, c; fucoxanthin
Dinophyceae (dinoflagellate) chlorophyll a, c; peridinin
Cryptophyceae chlorophyll a; phycobilins; carotenoids
17.3 TOXICOLOGY
Toxicity of algae is well known and can produce undesirable effects, causing sanitary problems or
harmful changes in the marine coastal water. Some bioxins from algae can affect both marine
animals and man. Humans can be affected through the digestive, respiratory organs, and the skin.
Although the biointoxications are mainly produced from marine animals, blue and blue-green algae
blooms release bioxins which affect skin and respiratory apparatus. Biointoxications by dinoflagel-
lates can be produced in four main ways: paralytic shellfish poisoning (P.S.P.), diarrhoetic shellfish
poisoning (D.S.P.), venerupin-poisoning, amnesic shellfish poisoning (A.S.P.) and the blue algae
blooms affecting the skin. All these marine toxins must be considered and special attention paid
in order to improve the knowledge of the compounds’ chemistry, toxicology, tolerance limits,
therapeutical approach antidotes, and remarks on safety. The eutrophication phenomena in marine
coastal waters can be explained by anthropogenic or by natural causes and both need a scientific
worldwide sanitary control.11
17.3.1 MICROCYSTINS
Microcystin L.R. is a potent cyclic heptapeptide hepatoxin that is produced by the blue-green algae
Microcystis aeruginosa. The algae is found in the Northern hemisphere and has been proven to be
one of the most potent inhibitors of type I and type II A protein phosphatases. Microcystin L.R.
induces alterations in the hepatocyte cytoskeleton, followed by hepatocyte disassociation, and cell
necrosis.
At the same time, Microcystin L.R. produces endothelial damage that allows the release of
cells and debris into the circulation system with microembolism occuring in the lungs and kidneys.
Rifampicin is effective against such toxicity when administered in animals (mice) at 25 mg/kg
dose, intraperitoneally, but only when injected close in time to exposure to the lethal toxin.14-16
The structures of Microcystins are unique with an unusual amino acid 3-amino-9-methoxy-10-
phenyl-2,6,8, trimethyl-deca 4 (E), 6 (E)-dienoic acid (Adda), that is thought to be significant for
the activity. Geometrical isomers at C-7 in the Adda portion of microcystins G (z) Adda microcystin
L.R. and R.R. have been isolated from Cyanobacteria. Both isomers bind to protein phosphatases
type I and type II A, inhibit their activities, and release glutamic pyruvic transaminase from rat
liver into serum in a very high proportion.
Microcystin L.R. is the best known microcystin. It is a heptapeptide containing leucine and
arginine. Microcystin L.R. has a potent tumor promoting activity in rat liver previously initiated
by experimental diethylnitrosamine. Microcystin L.R. inhibits protein activities of phosphatases.
This inhibition is similar to that of the known protein phosphatase inhibitor and tumor promoter
okadaic acid that is a tumor promoter factor in mouse skin, rat glandular stomach, and rat liver. In
fact, a natural product derived from a blue-green algae named microcystin is toxic and may produce
severe damage in the liver.17,18 That toxicity is completely abolished with a single dose of Silymarin,
a flavoliguane isolated from the wild artichoke Silybum marianum, L. Gaertn.19-21
Barcoo fever, Barcoo spews, Barcoo sickness, or simply the Barcoo is also a toxic disease that
looks like an infection illness produced by blue-green algae. The symptoms are similar to those
shown to be owing to the hepatotoxin of the tropical Cyanobacteria Cylindrospermopsis raciborskii
(Woloszynskn).22
17.3.2 CAULERPENYNE
Caulerpenyne is the most important of the bioactive secondary metabolites released by the algae
Caulerpa toxifolia (Vahl) and C. agardh. The extensive growth of that algae in the Mediterranean
Sea produces important quantities that justify the possible toxic effects of its bioactive metabolites.
These effects were studied in in vitro models. In these studies, primary cultured melanocytes,
keratinocytes, inmortalized keratinocytes (HaCaT), and (HESV) obtained from skin were used. In
addition, marrow cells and hemapoietic progenitors (CFU–GM) from bone were used. Hematopoi-
etic cells are more sensitive to caulerpenyne than skin derived cells. Nevertheless, the results suggest
that the risk for food intoxication or skin damage to humans from the invasive Mediterranean
Caulerpa toxifolia may be considered minimal based on the findings from these assays.23
Caulerpenyne was also tested against eight human cancer cell lines. The compound demon-
strated inhibitory growth effects in all cases with some variability between cell lines. The most
sensitive were cells of colorectal cancer. Cells in culture clearly exhibited an early and marked
shift into S phase followed by a blockade into the premitotic G.2.M. phase, although targets for
Caulerpa remain to be identified.24
17.3.4 PHEOPHORBIDE A
Pheophorbide A is a chlorophyll derivative present in the Chlorella algae speices. This compound
has been suggested to be a phototoxic and photoallergic substance. In Japan, where it is ingested
as an aphrodisiac in natural health food, phototoxic reactions have been reported in some
patients.26,27
17.3.5 PHYCOCYANIN
Phycocyanin is a blue pigment present in blue-green algae. This compound is considered to be a
contact sensitizer.28
Effects on proliferation of cultured cells and its relation to carcinogenesis have been evaluated.
The blue-green microalgae Spirulina fusiformis that is used in the daily diets of natives in Africa
and America, have been found to be a rich natural source of proteins, carotenoids, and other nutrients
like vitamin A, among many others. Studies have demostrated an inhibitory effect in animal
experimental oral carcinogenesis and reversing oral leukoplakia in pan tobacco chewers in India
by the oral intake of diet supplemented with Spirulina fusiformis.32
17.3.9 FUCOXANTHIN
Fucoxanthin, a natural carotenoid prepared from brown algae, inhibited the growth of GOTO cells,
a human neuroblastoma cell line. The amount of 10 mg per ml reduced the growth rate of GOTO
cells by 38 percent in the control by the arrest in the GO–G1 phase of the cell cycle.33
17.3.11 ARSENIC
Some algae like the brown seaweed U. pinnatifida (Wakame) contain Arsenic compounds. The
major organic arsenic compounds, termed arseno sugars, in marine algae commonly contain 5-
deoxy-5-dimethylarsinyl-ribofuranoside. Arsenobetain is not detected in marine algae or in fish,
mollusca, or crustacea. Both derivates probably have biological normal functions in these animals.35
17.3.13 PROTEOGLYCANS
It was very well known for over 50 years that a great variety of sulfated polysaccharides (pro-
teoglycans) were present in a large number of marine algae. These compounds have been shown
to have pharmacological anticoagulant properties.37,39
17.3.14 PHOCAMADIENE A
Phocamadiene A is a polyhalogenated monoterpene isolated from red marine algae of the Phoca-
mium genus. This substance causes histamine release from most cells in rats and guinea pigs. The
H2 histamine receptor antagonists Cimetedine and Ranitidine potentiate the response of phocama-
diene A. This activity has been measured by the contractions produced by the substances in the
gastrointestinal tract of the animals and was insensitive to atropine but significantly reduced by the
H1 histamine receptor antagonists.38,40
17.3.15 HEPOXILIN B3
Hepoxilin B3 is a 12 lipoxygenase metabolite of arachinodic acid that has been found in various
mammalian tissues. Although lipoxygenase pathways are well documented in terrestrial plants,
these pathways have also been identified for the first time in two marine plants: the tropical red
marine algae Platysiphonia miniata (C. agardh) Borgesen and Cottoniella filamentosa Borgesen.39,41
The oral administration of 1 g/kg per day of a crude extract of Gelidiella acerosa, a Sri Lankan
marine red algae, to rats caused a potential post coital contraceptive activity. This activity was due
to an elevated post implantation loss (by 89 percent) resulting from fetal death between 9–14 days
of pregnancy. The extract appeared to be antiprogestational (reduced ovarian progesterone output).
17.4.4 FRULLANIA
The probable cause of contact dermatitis observed in fishermen of anemones is the exposure to the
allergic compounds (frullanias) found in the moss Losthecium that grows among the moss. Previ-
ously, the Microciona, an animal named Ked moss, had been reported as the causative agent only
by intuitive suspicion.47,48
17.4.5 BIOTOXINS
Seabathers itch or papulovesicular eruptions are also produced by blue-green algae. Biotoxins
produced are mainly irritant sustances. Lyngbyotoxin A and Dermoaplysiatoxin are the toxic
products of Lyngbya majuscula, a blue-green algae. A similar papulovesicular eruption is caused
by Anabena, an alga that contain phycocyanin.49,50 The penetration of Lyngbyatoxin A in the human
and guinea pig skin has been measured. The method included skin disks of excised skin, mounted
in diffusion chambers, exposing the epidermal face to the air and the dermal portion bathed in a
buffered salt solution containing gentamycin sulfate. The epidermal surface were dosed with 26
micrograms of Lyngbyotoxin A per square centimeter in 13 microliters of dimethyl-sulfoxide per
square centimeter. The skin penetration was calculated by summing the amount of the toxin
recovered from the dermis and the receptor fluid. Penetration expressed as percentage of dose (n=3)
in guinea pig and human skin was 23 and 6.2 percent, respectively, after 1 h of topical exposure.51
17.4.6 PROTOTHECOSIS
Protothecosis are uncommon infections caused by Prototheca, considered to be an achlorophylous
algae. The genus Prototheca comprises several species, the most prevelant of which is Prototheca
wickerhamii. It is really an achlorophylons algae. This algae is found in the slime flux of trees and
fresh environs. The first reports of skin infections owing to this algae were noted about 30 years
ago. Asymptomatic and stationary cutaneous plaques may be seen in otherwise healthy patients,
although some systemic disease has been confirmed. Characteristic morula are seen histologically.
Antifungal therapy is the most effective medication.52
Nearly 80 human cases are reported since the first case was described by Davis and Wakelin
in 1964 in Sierra Leone. The disease has been identified in Europe, Asia (Thailand, China, and
Japan), Oceania, and the United States. In North America, most of the cases come from the
Southwest.
The main clinical manifestations are cutaneous lesions of papules, plaques, papulo-nodular
areas, and eczematous plaques, mainly located in the extremities. Bursitis of the olecranon occurred
in 25 percent of the patients. A tenosynovitis that followed median nerve release for carpal tunnel
syndrome has been published. Systemic protothecosis attacks also have been reported when an
immunosuppresive factor is present.
The first description of algae meningitis was reported in a patient with AIDS in association
with Cryptococcus neoformans. The histopathology shows a dermic granuloma with endospores.
The characteristic feature of protothecosis, in tissues, is the presence of the specific matura sporangia
of Prototheca wickerhamii with the pattern of morula. It is PAS positive and Grocott and Muci-
carmin positive.
17.5 REFERENCES
1. Tiffany, H. L., Algae, the Grass of Many Waters, Charles C. Thomas, Springfield, IL, 1968.
2. Chinetti, F. and Cariello, L., Gli animali marini velenosi e le loro tossine, Angelini G. and Vena G.
A., Eds., Lepetit, 1991, 57.
3. Brightman, F., The Oxford Book of Flowerless Plants, Oxford University Press, 1986.
4. Stern, K. R., Introductory Plant Biology, W. C. Brown Publishers, 1994, 286.
5. Kaufman, P. B., Plants. Their Biology and Importance, Harper & Row Publishers, 1989, 382.
6. Krogman, D. W., The low-potential cytochrome C of cyanobacteria and algae, Biochem. Biophys.
Acta, 1058, 35, 1991.
7. Brown, S. B., Houghton, J. D., and Vernon, D. I., Biosynthesis of phycobilins. Formation of the
chromophore of phytocrome phycocyanin and phycoerythrin, J. Protochem. Photobiol., 5, 3, 1990.
8. Bartley, G. E., Schmidhauser, T. J., Yanofsky, C., and Scolmik, P. A., Carotenoid desaturases from
Rhodobacter Capsulatus and Neurospora crassa are structurally and functionally conserved and
contain domains homologous to flavoprotein disulfide oxidoreductases, J. Biol. Chem., 265, 16020,
1990.
9. Ross, E. and Dowing, W., The nutritional value of dehydrated blue-green algae (Spirulina Platensis)
for poultry, Poult. Sci., 69, 794, 1990.
10. Gorindan, M., Hodge, J. D., Brown, K. A., and Nunes Smith, M., Distribution of cholesterol in
Caribbean marine algae, Steroids, 58, 178, 1993.
11. Viriani, R., Eutrophication, marine biotoxins, human health, Sci. Tot. Environ., Suppl., 631, 1992.
12. Solomon, A. E. and Stoughton R. B., Dermatitis from purified sea algae toxin (Debromoaphysiatoxin),
Arch. Dermatol., 114, 1333, 1978.
13. Cardellini, J. H., II, Marner, F. J., and Moore, R. E., Seaweed dermatitis: structure of lyngbyatoxin
A, Science, 204, 193, 1979.
14. Herwansky, S. J., Wolff, S. N., and Stohs, S. J., Use of Rifampin as an effective chemoprotectant and
antidote agains microcystin L.R. toxiciy, Pharmacology, 41, 231, 1990.
15. Honkanen, R. E., Zwiller, J., Moore, R. E., Daily, S. L., Khatra, B. S., Dukelow, M., and Boynton,
A. L., Characterization of Microcystin L.R., a potent inhibitor of type I and type II A protein
phosphatases, J. Biol. Chem., 265, 19401, 1990.
16. Hooser, S. B., Beasley, V. R., Basgall, E. J., Charmichal, W. W., and Haschek, W. M., Microcystin
L.R. induced ultrastructural changes in rats, Vet. Pathol., 27, 9, 1990.
17. Nishiwaki-Matsushima, R., Ohta, T., Nishiwaki, S., Suganuma, M., Kohyama, K., Ishikawa, T.,
Charmichael, W. W., and Fujiki, H., Liver tumor promotion by the Cyanobacterial cyclic peptide toxin
Microcystin L.R., J. Cancer Res. Clin. Oncol., 118, 420, 1992.
18. Nishiwaki-Matsushima, R., Ohta, T., Nishiwaki, S., Yoshizawa, S., Suganuma, M., Harada, K.,
Watanabe, M. F., and Fujiki, H., Structure-function relationships of Microcystins, liver tumor pro-
motes, in interaction with protein phosphatase, Jpn. J. Cancer Res., 82, 993, 1991.
CONTENTS
18.1 Introduction
18.1.1 Alstroemeriaceae
18.1.1.1 Taxonomic Position
18.1.1.2 Morphology
18.1.1.3 Cytogenetics
18.1.1.4 Ethnobotany
18.1.2 Alstroemeria L
18.1.2.1 Geographic Distribution and Ecology
18.1.2.2 Morphology
18.1.2.3 Systematics
18.1.2.4 Species of Horticultural Interest
18.1.2.5 Production
18.1.3 Bomarea Mirb.
18.1.4 Leontochir Phil.
18.1.5 Schickendantzia Pax
18.2 Chemistry
18.2.1 Anthocyanins and Other Flavonoids
18.2.2 Tuliposides
18.2.3 Extraction, Isolation, and Quantification of Tuliposides
18.2.4 Function and Biosynthesis of Tuliposides and Tulipalins
18.2.5 Reduction of Allergen Content
18.2.5.1 Genotypic Variation and Environmental Effects
18.2.5.2 Inheritance of Tuliposides and Breeding for Low
Allergen Content
18.3 Clinical Effects
18.3.1 Allergenic Principles
18.3.2 Dermatitis
18.3.3 Patch Testing
18.4 Acknowledgments
18.5 References
18.1 INTRODUCTION
Within Alstroemeriaceae, only the genus Alstroemeria has major commercial interest. Interspecific
hybrids of Alstroemeria are cultivated in greenhouses for cut-flower production, increasing in
importance since the 1960s. In relation to the large scale cultivation of Alstroemeria, the attention
18.1.1 ALSTROEMERIACEAE
18.1.1.1 Taxonomic position
18.1.1.2 Morphology
18.1.1.3 Cytogenetics
18.1.1.4 Ethnobotany
Both Alstroemeria and Bomarea have been used in traditional medicine,33-36 the storage roots as
food,3-5,33,36,38 the stems chewed as candy,39 and stems of Bomarea have been used in house
construction in Columbia.36 Extracts of leaves have been used against angina and hemorrhoids, the
roots have been used as a diuretic, and the tonic against cystitis,33 as well as against sterility.36 The
starch of the roots is easy to digest and should be good for children and people with digestive
problems.37 The roots are either cooked11,37 or roasted.33 The medicinal effects and food qualities
may depend on genera and species because different species are mentioned for different purposes.
However, the small qualitative differences in chemical compounds among species indicate that
several species might have similar effects. From the present chemical analyses of the family, it is
difficult to point out the compounds active against diseases. It may be saponins that have hemolytic
effects40 and/or chelodonic acid,41 both detected in Alstroemeria.
18.1.2 ALSTROEMERIA L.
Several of the popular names, for example, Inca Lily, Peruvian Lily, and Parrot Lily, reflect the
geographic origin of the genus and the vividly colored, showy flowers.
Alstroemeria with the type species A. pelegrina L. was first described by the French priest R.
P. Louis Feuillèe in 1714. Feuillèe described three species referring them to the genus Hemerocallis
(Day Lily): Hemerocallis salsilla (equivalent to Bomarea salsilla (L.) Herb.), H. pelegrina (now
Alstroemeria pelegrina L.), and H. ligtu (now Alstroemeria ligtu L.). The genus Alstroemeria was
established by Linneaus in 1761 in honor of one of his students, Claes von Alströmer (1736-1794),
who sent him seeds from the Swedish consulate in Cadiz, Spain.42
Looking through literature, more than 225 Alstroemeria epithets have been recorded.2,10,43-48
Most of these are synonyms and several of the names are now referred to the genus Bomarea. At
present, about 50 Alstroemeria species are recognized. Bayer44 recognizes 31 Alstroemeria species
from Chile (41 taxa), reporting 130 synonyms. Further, 18 Chilean species have been described by
Main centers of distribution for Alstroemeria are Central Chile and the southern and eastern parts
of Brazil with extensions into Paraguay, Argentina, and Peru.21,47 The distribution area of Alstro-
emeria covers different climates and ecological zones with many species adapted to rather specific
habitats.44,51 In Chile, Alstroemeria is found from 22° S in the north (A. graminea Phil. and A.
paupercula Phil.) down south to Patagonia (51° S) (A. patagonica Phil.), a distance of more than
3000 km. Some species are lowland plants growing at the shore of the Pacific Ocean (e.g., A.
hookeri Lodd. and A. pelegrina), whereas other species are alpine plants adapted to the Andes
at altitudes up to 3500 m (A. andina Phil. and A. spathulata C. Presl). Alstroemeria species grow
in sand, semishaded woodlands, at steep rocky slopes, at dry screes, and they are often found
in newly disturbed areas.44,51 In Brazil, some species are found in the rain forests of the tropical
Amazon and in river marshes;21,43 however, the largest number of Brazilian species is found in
the Cerrado (e.g., the province Minas Gerais) in the central and southeastern part at altitudes of
more than 1000 m.
Many of the Chilean species are adapted to short winter rainfalls presenting a limited growth
period with leaves often withering before seed set is accomplished. The rhizomes are in a dormant
stage during the summer drought, triggered to sprout only if sufficient precipitation falls during
winter time. In the arid desert areas of the northern Chile, the precipitation in some years is
insufficient for the plants to flower. They then survive as dormant rhizomes or as seeds. In Brazil,
the longer rainy season provides conditions enabling vegetative growth for a longer period with
some species even being evergreens.2,47 Several of the Brazilian species form large continuous and
dense populations,47 as do A. pelegrina in Chile and A. aurea in Chile and Argentina.44,50,51
In older literature1,2,52 and also in a recent checklist10 the species concepts remain diffuse and
confusing, obviously resulting in misinterpretations of species, for example, A. pelegrina and A.
ligtu have been considered as one species52 as have A. ligtu and A. pulchella L. f.43 Records of A.
pelegrina in the Peruvian Andes at altitudes of up to 3500 m10 may likewise refer to misidentified
species because A. pelegrina in Chile is restricted to altitudes below 300 m along the Pacific coast
around Valparaiso.44,51 The two Brazilian species A. inodora Herb. and A. pulchella are described
as being closely related to the Chilean A. haemantha Ruìz & Pav. (equivalent to A. ligtu ssp. simsii)
and A. aurantiaca (syn. A. aurea),2 but the two Chilean species are easily distinguished morpho-
logically from another and clearly differ from the two Brazilian species. The Chilean A. ligtu and
the Brazilian A. caryophyllea Jacq. have also been referred to as one species, but this misinterpre-
tation can be ascribed to a misstatement in The Botanical Magazine.1,43 There are also other incidents
of A. ligtu being misidentified.43
18.1.2.2 Morphology
The Chilean and Brazilian species are distinguishable both at the morphological and at the molecular
level. The Chilean species are most often slender plants with linear to lanceolate leaves and with
open cup-shaped, large, and showy flowers in bright colors. A. hookeri, A. pallida Graham, and
18.1.2.3 Systematics
Based on morphological data, Bayer44 groups A. pulchra Sims, A. magenta Bayer, and A. magnifica
and, likewise, A. hookeri, A. angustifolia, and A. pallida, as well as A. ligtu, A. aurea, and A.
presliana Herb., but Bayer does not find it possible to discuss the relationships between groups or
the phylogenetic evolution of the genus. From estimations of nuclear DNA content by flow
cytometry26 and by characterization of karyotypes by Giemsa C-banding,28 the investigated Alstro-
emeria species could be arranged in four groups: Group 1—A. magnifica, A. pelegrina, A. philippii
Baker, and A. pulchra; Group 2—A. angustifolia, A. aurea, and A. hookeri; Group 3—A. ligtu ssp.
ligtu and A. ligtu ssp. simsii; and Group 4—the Brazilian species (A. brasiliensis Spreng., A.
caryophyllea, A. inodora, and A. psittacina). The morphological, cytological, and chemical data
(see Sections 18.2.1 and 18.2.2) provides, however, no consistent systematic grouping of the genus
at present except that the Chilean and the Brazilian species seem to be distinct taxonomic units.
The differences in karyotypes suggest an early separation of the Chilean and the Brazilian species
after which speciation followed different evolutionary pathways.28
Alstroemeria aurea Graham (syn. A. aurantiaca D. Don)—the distribution area extends from
36° S to 42° S in Chile with extension into the Argentinean Andes.44,50,55 It is found from almost
sea level up to altitudes of 2000 m inhabiting arable areas, semishaded Nothofagus forests, and
open mountain screes.44,50,51,55 The inflorescence has up to 15 relatively large flowers in yellow to
red colors with a very variable patterning of dots and stripes. Leaves are up to 14 · 2 cm and
almost without undulated margins. Specimen selections (e.g., cv’s ‘Lutea,’ ‘Orange King,’ and
‘Splendens’) are cultivated as ornamental perennials in gardens throughout Europe and America.
A. aurea has been used in interspecific hybridizations to produce cut flower cultivars. ‘Walter
Fleming’ is a diploid, sterile hybrid between A. aurea and A. paupercula made in the 1930s. A
fertile, tetraploid sport was later crossed with other diploid species to produce the sterile triploid
(2n = 3x = 24) Orchid hybrids.61 The first hybrid between A. aurea and A. pelegrina appeared in
early 1960s with the introduction of ‘Regina’ from the Dutch company van Staveren56; ‘Regina’
is still a cultivar of major importance.57
Alstroemeria pelegrina L. (Figure 18.1)—this generic type species was described by Linneaus
in 1761. Morphologically, it is distinguished by somewhat succulent leaves, large flowers (7 cm in
18.1.2.5 Production
Alstroemeria has become an important cut flower because of its large, vividly colored, long-lasting
flowers. Since the 1990s, Alstroemeria has been among the first ten cut-flower species on the Dutch
market. The production area in The Netherlands was about 115 ha and 400 ha were grown in the
18.2 CHEMISTRY
The chemical investigations carried out so far on species in Alstroemeriaceae have primarily been
on anthocyanins, other flavonoids, and tuliposides. Other constituents present in this family are
sterols, hydrocarbons, caffeic acid, p-coumaric acid, and chelidonic acid, that so far has only been
isolated from Alstroemeria aurea.41,87,88 Furthermore, the presence of saponins in many Alstroeme-
riaceae species have been indicated, although their chemical structures still remain to be deter-
mined.40 Finally, alkaloids do not seem to be present in Alstroemeriaceae, although they are widely
distributed in Amaryllidaceae.89
bathochromic wavelenght shift in the visible lmax of the anthocyanins which makes them appear
bluer.90 Although flavone and flavonol glycosides are present in relatively large amounts in the
flowers of Alstroemeria species, their chemical structures have not been determined.90 However,
they may be closely related to or even identical with some of the leaf flavonoids found in Bomarea
caldasiana Herb. and a few Alstroemeria species (see Table 18.1). The yellow flowers in some
Alstroemeria species and the intensively yellow patches in most species are caused by carotenoids.90
The chemical structure of the carotenoids have not been determined so far. Beside the leaf flavonoids
in Bomarea, pigments have only been investigated in the genus Alstroemeria (Table 18.1).
The anthocyanins found in Alstroemeria are widely distributed in many other genera91,92 except
those having three hydroxy groups in the A-ring, i.e., 6-hydroxycyanidin 3-glucoside (3), 6-hydroxy-
cyanindin 3-rutinoside (6), and 6-hydroxydelphinidin 3-rutinoside (7) (Figure 18.5) that only seem
to be present in the genus Alstroemeria.90,93-96 The majority of the investigated Alstroemeria species
can be placed into three groups according to their content of major anthocyanins. The species in
Group 1
A. angustifolia ssp. angustifolia Herb. 4, 6 1, 2 90, 95
A. aurea Graham (syn. A. aurantiaca D. Don)b 4, 6 94, 95
A. exserens Meyen 4, 6 1c 95
A. garaventae Bayer 4, 6 95
A. ligtu ssp. ligtu L. 4, 6 94, 95
A. ligtu ssp. simsii Bayer 4, 6 94, 95
(syn. A. haemantha Ruìz & Pav.)
A. pallida Graham 4, 6 1c 95
A. presliana ssp. presliana Herb. 4, 6 1, 2, 5c 95
A. pseudospathulata Bayer 4, 6 95
A. versicolor Ruìz & Pav. 4, 6 2, 5 90, 95
Group 2
A. diluta ssp. diluta Bayer 1, 4 6 95
A. diluta ssp. chrysantha Bayer 1, 4 6 95
A. hookeri ssp. hookeri Lodd. 1, 4 5, 6 95
(syns. A. rosea Hook., A. hookeriana Schult.)
A. hookeri ssp. recumbens Bayer 1, 4 5, 6 95
A. leporina Bayer & Grau 1, 4 6c 95
A. magnifica Herb. ssp. maxima Bayer 1, 4 5c 95
A. pelegrina L. 1, 4 5, 6 90, 94, 95
Group 3
A. magenta Bayer 1, 2, 4, 5 7 95
(syn. A. violacea Phil.)
A. paupercula Phil. 1, 2, 4, 5 94, 95
A. philippii Baker 1, 2, 4, 5 7 95
A. polyphylla Phil. 1, 2, 4, 5 95
A. pulchra ssp. pulchra Sims 1, 2, 4, 5 7 8–12 95, 174
A. pulchra ssp. maxima Phil. 1, 2, 4, 5 7 95
A. revoluta Ruìz & Pav. 1, 2, 4, 5 7 95
A. werdermannii Bayer 1, 2, 4, 5 7 95
Beyond groups
A. brasiliensis Spreng. Kaempferold 175
A. hookeri ssp. cummingiana Bayer 4 1, 6c 95
A. pelegrina var. alba Quercetin,d 175
Kaempferold
A. presliana Herb. ssp. australis Bayer 1, 4, 6c 95
A. pulchella L. f. (syn. A. psittacina Lehm) Kaempferold 175
A. schizanthoides Grau 2 1, 4, 5 95
Bomarea caldasiana Herb. Kaempferold 175
a Author names (Alstroemeria) in accordance with Bayer.44
b Synonyms are given in parentheses when they are necessary to prevent confusion.
c Contains an acylated 6-hydroxycyanidin 3-rutinoside also.
d Isolated as a glycoside, but the glycoside part has not been identified.
the first group contain cyanidin 3-rutinoside (4) and 6-hydroxycyanidin 3-rutinoside (6), whereas
the second group is characterized by having cyanidin 3-malonylglucoside (1) and cyanidin 3-
rutinoside (4) as major anthocyanins. The major anthocyanins in the third group are the 3-rutinosides
and 3-malonylglucosides of cyanidin (1, 4) and delphinidin (2, 5) (Table 18.1; Figure 18.5). From
a chemotaxonomic point of view, species in the first group seem to be related as 6-hydroxycyanidin
3-rutinoside is only found as a minor anthocyanin in the third group and in a few species beyond
this grouping (Table 18.1). The presence of cyanidin 3-malonylglucoside as a major anthocyanin
in the second group indicates a relationship between species of this group, because the ability to
produce acylated anthocyanins seems to be limited to about 1/2 of the investigated species (Table
18.1). The species in the third group seem closely related because, for example, they produce
delphinidin glycosides that are present only sporadically as minor constituents in the first and
second group (Table 18.1). A. hookeri ssp. cummingiana (Herb.) Bayer, A. presliana ssp. australis,
and A. schizanthoides do not fit precisely in the preceding grouping. However, A. presliana ssp.
australis seems to be related to species of the first group owing to the presence of 6-hydroxycyanidin
3-rutinoside as one of the major anthocyanins, whereas the anthocyanin composition in A. hookeri
ssp. cummingiana indicates a relationship to the species in the second group. A. schizanthoides is
different from the other species because it only contains delphinidin 3-malonylglucoside as a major
anthocyanin (Table 18.1). The anthocyanin composition of the majority of the Alstroemeria cultivars
do not fit into the grouping, probably because they are interspecific hybrids (Table 18.2). 6-Hydroxy-
cyanidin 3-glucoside (3) has only been detected in cultivars, for example, and not in the species.
The flower color is one of the most important characteristics in the breeding of ornamental
plants. In order to create desired flower colors it is an advantage to know the relationship between
the color and the contents of the pigments and their inheritance. Nørbæk et al.90 recently determined
the major anthocyanins in 28 Alstroemeria species and 183 interspecific hybrids, and a model
describing the effects of anthocyanin and co-pigments on Alstroemeria flower color was established.
The model includes four chemical characteristics: the total anthocyanin concentration, the ratio of
anthocyanins to flavonoids, the relative content of different aglycones, and the percentage of
malonated anthocyanins. Regarding the inheritance of these characteristics a high correlation
between parents and hybrids was found for the relative contents of different aglycones. For example,
the percentage of 6-hydroxycyanindin 3-glycosides in the offspring corresponded to the average
in their parents. For malonated anthocyanins, most often the average percentage in parents was
found in offspring. The anthocyanin concentration in the hybrids was somewhat lower than the
average of their parents. The inheritance of these three characteristics seems mainly to be controlled
by additive genes. The anthocyanin/flavonoid ratio in a hybrid often deviated strongly from the
average of the parents and no systematic tendency was apparent. Thus, the inheritance could not
be determined for this characteristic. The previous investigation could be quite valuable for selection
of parents in the breeding of new cultivars with specific colors and thereby expand the market for
Alstroemeria cut flowers.
from 1-tuliposide A during extraction and isolation.101,107-111 The NMR data of 6-tuliposide A showed
that it exists both as the b- and a-anomer.101,107-109 From the integrals of the two anomeric C-1
protons appearing at d 4.62 (b) and 5.17 (a) in the 1H NMR spectrum (recorded in D2O), the
anomeric equilibrium was determined to be 3:2 at room temperature. This is consistent with the
RP–HPLC chromatograms shown in Figure 18.7, 18.8a, and 18.8b. 6-Tuliposide A may, therefore,
be the only natural acyl derivative of tuliposide A in species of Alstroemeriaceae, although the
presence of 1-tuliposide A cannot theoretically be excluded. Recent investigations of several Tulipa
cultivars and species by RP–HPLC gave similar results as only the 6-acyl derivatives of tuliposide
A and B were detected.112 Several papers on the distribution of tuliposides in Liliaceae have
appeared,104-106 but because only Tschesche et al.102,103 investigated the position of the acyl group
on D-glucose, it is still uncertain which acyl derivative of tuliposide A and B is most common in
Liliaceae. The presence of a third tuliposide (tuliposide C) in T. gesneriana have also been
indicated,102,103 but this compound has not been identified. A tuliposide with a 4-hydroxy-2-meth-
ylenebutanoate moiety in both the 1- and 6-position of b-D-glucose (tuliposide D, 17) have recently
been found in Alstroemeria species together with a closely related derivative (tuliposide E, 18)
(Figure 18.6).107-111 However, we also have been able to detect tuliposide D in some Tulipa species
of which T. patens contained relatively large amounts of this compound.112 The presence of
tuliposide D and E in Alstroemeriaceae and tuliposide D in Liliaceae is interesting from a biogenetic,
chemotaxonomic, and allergenic point of view.
Tulipalin A was isolated in 1946 from Erythronium americanum (Liliaceae)113 and later from
tulips.97,114 It has been considered only to be formed from tuliposides after excision of plant parts.98,99
However, the concentrations of tuliposides and tulipalin A immediately after homogenization of
fresh plants have recently been shown not to change over several days, clearly indicating that
tulipalin A is present in situ in the plants.101,108,110,111 This is also in accord with the different amounts
of tulipalin A found in leaves, stems, and flowers (Table 18.3).101,108,110,111 The content of tulipalin
A in the plants is probably influenced by the environment (e.g., development stage, pest attatcks,
drought), although it cannot be excluded that tulipalin A is formed after cutting and that a high
TABLE 18.3
The Highest Concentrations of 6-Tuliposide A (15), Tuliposide D (17), Tuliposide E (18), and Tulipalin A (19) in Leaves (L), Stems (S) and
Flowers (F) of Species Belonging to the Genera Alstroemeria, Bomarea, and Leontochir108
6-Tuliposide A Tuliposide D Tuliposide E Tulipalin A
Genus/Speciesa and Cultivars L S F L S F L S F L S F References
—: not investigated; n: not detectable; t: trace; 1+ between 0.01 and 0.05 percent; 2+ between 0.05 and 0.15 percent; 3+ between 0.15 and 0.3 percent; 4+ between 0.3 and 0.5 percent;
5+ between 0.5 and 0.7 percent; 6+ between 0.7 and 1.0 percent; 7+ between 1.0 and 1.5 percent; 8+ more than 1.5 percent in fresh plant tissue.
a Author names (Alstroemeria) in accordance with Bayer.44 Synonyms of species are given in parentheses (see also Table 18.1).
b The highest concentration of 6-tuliposide A, tuliposide D, E, and tulipalin A in the investigated species of Alstroemeria, Bomarea, and Leontochir is given. However, as a large genotypic
variation is found within most species, the content in individual plants are most likely smaller at least for some of the compounds.
c The identity of the species investigated is uncertain. The most probable identity and synonym are given in parentheses.
d The content of 6-tuliposide A is much higher in this plant part according to Slob et al.105
FIGURE 18.7 An analytical HPLC chromatogram of an aqueous extract of Alstroemeria revoluta Ruìz &
Pav. stems separated on a LiChrospher 100 RP-18 (5 mm; 244 · 4 mm) column using a gradient solvent
system consisting of solvent A (distilled water — MeOH, 80:20) and solvent B (distilled water — MeOH,
50:50); elution profile: 0–6 min 0 % B, 40 min 100 % B, 45–60 min 0 % B; flow:0.6 ml min-1.
Tuliposides so far have been found only in Alstroemeriaceae and Liliaceae and these com-
pounds, therefore, seem to be useful in chemotaxonomic evaluations. To discriminate between
Alstroemeriaceae and Liliaceae tuliposide B seem to be a valuable taxonomic marker due to its
absence in the former family.
simple isocratic elution. A mobile phase of 20 percent MeOH and a flow rate of 0.6 ml min-1 give
a good separation as shown in Figure 18.8a. For determination of the contents of 6-tuliposide A,
tuliposide D, and tulipalin A, this method is preferable compared to the gradient elution owing to
its simplicity and speed. If many samples are to be analysed, speed can be increased further by
only analyzing for 6-tuliposide A and tulipalin A. From an allergenic point of view this can be
justified as tuliposide D and E most often only are present in small amounts (Tables 18.3 and 18.4).
The contents of 6-tuliposide A and tulipalin A in extracts can be analyzed within 15 minutes on a
LiChrospher 100 RP-18 (5 mm; 244 · 4 mm) column using isocratic elution with 10 percent MeOH
and a flow rate of 0.8 ml min-1 as shown in Figure 18.8b. This method is not only fast but also
gives a very good separation of the two isomers of 6-tuliposide A. Furthermore, it separates
tuliposide B from tuliposide A and other components in extracts. Thus, this method would be the
one to choose for the determination of tuliposide A and B in the Tulipa species, for example.
Tuliposides and tulipalin A are quantified in extracts by using pure compounds for calibration.
The compounds are isolated by preparative HPLC or CC from crude water extracts. Isolation of
each component by preparative HPLC follows almost the same procedures as for analytical
separation, although the flow and injection volume are much higher.101,108 Tuliposides also can be
isolated easily by CC over silicagel using a gradient consisting of different proportions of chloro-
form, methanol, and water.107,109
fungicidal activity, whereas 6-tuliposide A and B did not possess antibiotic properties. The antibiotic
activities of tulipalin A and B have recieved much attention and their role as fungitoxic agents is
now well documented.114,116-122 They appear, however, ineffective against the fungus Botrytis tulipae
that causes gray mould disease of tulips.118 Although the antibiotic properties of tuliposide D and
E have not been investigated, the present results indicate that the tuliposides in Alstroemeriaceae
are not directly involved in resistance against diseases. It is more likely that they are storage products
for the antibiotic tulipalin A that is formed from tuliposides by enzymatic hydrolysis in vivo.116,117,119
This has been confirmed in experiments where cold stored cut flowers attacked by fungi had a very
low content of 6-tuliposide A but an extremely high content of tulipalin A as compared to nonat-
tacked flowers.112 Tulipalin A may, therefore, be regarded as a post inhibitin that is present only in
relatively small amounts in uninfected plant tissue but is released in large amounts upon infection
in order to express full toxicity. The high concentrations of 6-tuliposide A and tuliposide D (total
up to 3.8 percent fresh weight) are found in some plants112 and their simple chemical structure also
indicate other functions; they may be primary metabolites functioning as storage compounds for
D-glucose or regulators of osmolarity.
The biosynthesis of tuliposides has not been investigated directly, but their chemical structure
indicates it to be rather simple. It is reasonable to assume that tuliposides are biosynthesized from
b-D-glucose and 4-hydroxy-2-methylenebutanoic acid (HMBA). A condensation between b-D-
glucose and HMBA with the loss of water would give 6-tuliposide A or 1-tuliposide A (Figure
18.11). Further condensation with HMBA leads to tuliposide D and E as shown in Figure 18.11.
Enzymatic hydrolysis of the tuliposides leads to tulipalin A and b-D-glucose and tuliposides are,
therefore as previously stated, precursors to tulipalin A. The latter has been confirmed in a
The concentrations of 6-tuliposide A and tulipalin A in different plant parts of Alstroemeria species
vary considerably among genotypes.111 The largest variations have been found so far in A. aurea,
A. ligtu ssp. ligtu, and A. pallida where the coefficients of variation in the 6-tuliposide A and
The antibiotic activities of tulipalin A indicate that tuliposides at least indirectly are involved in
resistance against fungi (see Section 18.2.4) and changes in allergenic properties may, therefore,
affect resistance. Tulips contain the nonallergenic tuliposide B that is also the precursor to the
antibiotic tulipalin B, so it is theoretically possible to breed tulip cultivars with low tuliposide A
and high tuliposide B/tulipalin B content. In Alstroemeria, the situation is more complicated as
tuliposide B and tulipalin B are not present and it seems not possible, therefore, to produce
nonallergenic Alstroemeria cultivars without affecting resistance. However, as the risk for sensiti-
zation increases with allergen concentration, it should be possible to produce relative nonsensitizing
cultivars with low content of tuliposides and tulipalin A.
The inheritance of tuliposides in Alstroemeria and the possibility to produce Alstroemeria
cultivars with low content of allergens by cross breeding have recently been investigated.111 The
inheritance of tuliposides was investigated by testing the resemblance between parents and their
offspring for tulipalin A, 6-tuliposide A, tuliposide D, and total allergen content (Figure 18.10).
Narrow sense heritability of the different allergens in the different plant parts was estimated by
linear regression of the offspring value on the average of the parents. Significant heritabilities were
found for the concentration of 6-tuliposide A and tuliposide D, as well as for the total allergen
content.111 The heritability of tulipalin A was not significant, supporting the assumption that the
content of tulipalin A is controlled mostly by the environment (see Sections 18.2.4 and 18.2.5.1).
The significant and high heritabilities indicate that the production of tuliposides is controlled by
additive genes that also are expected considering the variability found within Alstroemeria species.
Several breeding generations will, therefore, be necessary before relatively nonsensitizing cultivars
can be introduced to the market. Furthermore, it also has been shown that it is possible to reduce
the allergen content by mutagenesis.111 However, to produce Alstroemeria cultivars totally without
allergens must be considered very difficult or even impossible.
18.3.2 DERMATITIS
All genera of the Alstroemeriaceae, except Leontochir, contain tuliposides and tulipalin A (Table
18.3), so it is reasonable to assume that the allergenic potential characterize the family. So far only
Alstroemeria have been shown to be a strong sensitizer and several cases of occupational contact
dermatitis owing to Alstroemeria have been reported.99,100,141-159 Allergic contact dermatitis to Alstro-
emeria appears to have a latent onset. Hausen et al.99 reported a delay of 19 months to 3 years
18.4 ACKNOWLEDGMENTS
Plant material of Bomarea and Tulipa were provided kindly by the botanical gardens of Missouri,
Edinburgh, Munich, and Copenhagen as well as the Royal Veterinary and Agricultural University,
Copenhagen. Plants of Leontochir were obtained from Prof. M. Bridgen, University of Connecticut.
The chemical analyses of the allergens were partly financed by the Danish Agricultural and
18.5 REFERENCES
1. Herbert, W. M., Amaryllidaceae, James Ridgway & Sons, Piccadilly, London, 1837, 1.
2. Baker, J. G., Handbook of the Amaryllideæ Including Alstræmerieæ and Agaveæ, George Bell & Sons,
London, UK, 1888, 132.
3. Pax, F., Amaryllidaceae, in Die natürlichen Pflanzenfamilien, Engler, A. and Prantl, K., Eds., 2, 97,
1888.
4. Pax, F., Beiträge zur Kenntnis der Amaryllidaceae, Botanischer Jahrbücher für Systematik, Pflanz.
Pflanzengeogr., 11, 318, 1890.
5. Pax, F. and Hoffmann, K., Amaryllidaceae, in Die Natürlichen Pflanzenfamilien nebst ihren Gattungen
und wichtigeren Arten, insbesondere den Nutzpflanzen, Engler, A. and Prantl, K., Eds., 2nd ed., 1930,
15a, 391.
6. Traub, H. P., An introduction to Herbert’s “Amaryllidaceae, etc.” 1837 and Related works, Verlag
von J. Cramer, Lehre, 1970.
7. Buxbaum, F., Morphologie der Blüte und Frucht von Alstroemeria und der Anschluss der Alstroeme-
rioideae bei den echten Liliaceae, Österr. Botan. Z., 101, 23, 1954.
8. Melchior, H., 3. Reihe Liliiflorae (Liliales), in A. Engler’s Syllabus der Pflanzenfamilien mit beson-
derer Berücksichtigung der Nutzpflanzen nebst einer Übersicht über die Florenreiche und Florenge-
biete der Erde, 12th ed., 1964, 2, 513.
9. Jørgensen, P. M. and Ulloa Ulloa, C., Seed plants of the high Andes of Ecuador—a checklist, AAU
Rep., 34, 239, 1994.
10. Brako, L. and Zarucchi, J. L., Catalogue of the flowering plants and gymnosperms of Peru, MO Bot.
Gard., 1995.
11. Dahlgren, R. M. T., Clifford, H. T., and Yeo, P. F., The Families of the Monocotyledons—Structure,
Evolution, and Taxonomy, Springer-Verlag, Berlin, 1985, 220.
12. Takhtajan, A., Flowering Plants—Origin and Dispersal, Oliver & Boyd: Edinburgh, 1969.
13. Hutchinson J., The Families of Flowering Plants Arranged According to a New System Based on
Their Phylogeny, Otto Koeltz Science Publishers, Koenigstein, Germany, 1979.
14. Chase, M. W., Soltis, D. E., Olmstead, R. G., Morgan, D., Les, D. H., Mishler, B. D., Duvall, M. R.,
Price, R. A., Hills, H. G., Qiu, Y.-L., Kron, K. A., Rettig, J. H., Conti, E., Palmer, J. D., Manhart, J.
R., Sytsma, K. J., Michaels, H. J., Kress, W. J., Karol, K. G., Clark, W. D., Hedrén, M., Gaut, B. S.,
Jansen, R. K., Kim, K.-J., Wimpee, C. F., Smith, J. F., Furnier, G. R., Strauss, S. H., Xiang, Q.-Y.,
Plunkett, G. M., Soltis, P. S., Swensen, S. M., Williams, S. E., Gadek, P. A., Quinn, C. J., Eguiarte,
L. E., Golenberg, E., Learn, Jr., G. H., Graham, S. W., Barret, S. C. H., Dayanandan, S., and Albert,
V. A., Phylogenetics of seed plants: an analysis of nucleotide sequences from the plastid gene rbcL,
Ann. MO Bot. Gard., 80, 528, 1993.
15. Ørgaard, M., Kristiansen, K., and Jacobsen, N., unpublished data, 1998.
16. Traub, H. P., Nectaries in Alstroemeria pulchella, Plant Life, 122, 1966.
17. Snow, A. A. and Grove, K. F., Protandry, a neuter phase, and unisexual umbels in a hermaphroditic,
neotropical vine (Bomarea acutifolia, Alstroemeriaceae), Am. J. Bot., 82, 741, 1995.
18. Aizen, M. A. and Basilio, A., Within and among flower sex-phase distribution in Alstroemeria aurea
(Alstroemeriaceae), Can. J. Bot., 73, 1986, 1995.
19. Schulze, W., Beiträge zur Taxonomie der Liliifloren. III. Alstroemeriaceae, Wiss. Z. Friedrich-Schiller-
Univ. Jena, Math.-Nat. R., 27, 79, 1978.
20. De Jeu, M. J., Calderè, F. C., and van Went, J. L. Sporogenesis, gametogenesis, and progamic phase
in Alstroemeria, Can J. Bot., 74, 1354, 1996.
21. Aker, S. and Healy, W., The phytogeography of the genus Alstroemeria, Herbertia, 46, 76, 1990.
CONTENTS
19.1 Introduction
19.1.1 Morphological Characteristics of the Plant Family
19.1.2 Geographical Location
19.2 Chemical Constituents
19.2.1 Aristolochia Spp
19.2.1.1 Nitrogenated Constituents
19.2.1.1.1 Phenanthrene Derivatives
19.2.1.1.2 Alkaloids
19.2.1.2 Constituents without Nitrogen
19.2.1.2.1 Terpenoids
19.2.1.2.2 Lignoids
19.2.1.2.3 Flavonoids
19.2.2 Asarum Spp
19.2.3 Heterotropa Spp
19.2.4 Asiasarum Spp
19.2.5 Thottea Spp
19.2.6 Pararistolochia Spp
19.2.7 Hexastylis Spp
19.2.8 Saruma Spp
19.3 Pharmacology and Clinical Use
19.3.1 Aristolochia Spp
19.3.1.1 Pharmacology
19.3.1.1.1 Antitumor Activity
19.3.1.1.2 Immunomodulating Activity
19.3.1.1.3 Antibacterial and Antifungal Action
19.3.1.1.4 Antifertility Activity
19.3.1.1.5 Hypotensive Action
19.3.1.1.6 Miscellaneous Actions and Toxicity
19.3.1.2 Clinical Use
19.3.1.3 Dermatological Use
19.3.2 Asarum Spp
19.3.2.1 Pharmacology
19.3.2.1.1 Sedative and Analgesic Effects
19.3.2.1.2 Antipyretic and Anti-Inflammatory Effects
19.3.2.1.3 Local Anesthetic Activity
19.3.2.1.4 Antibacterial and Antifungal Activity
19.3.2.1.5 Antihistaminic and Anti-allergic Effects
19.1 INTRODUCTION
Aristolochiaceae (the Birthwort family) is a family of twining shrubs, lianes, vines, perennial herbs,
that usually are rhizomatous and fragrant. The family consists of 7 to 8 genera and 450 to 600
species, mainly widespread in the Tropics, with a few species in subtropical and temperate regions
of the Old and the New World.
The common name of the family seems to be derived from two Greek words: aristos meaning
best or, excellent, and lochia meaning delivery. This name concerns the genus Aristolochia that is
used as a medicinal herb during childbirth.
The common name of Aristolochia L. is Dutchman’s pipe vine, referring to the unusually
shaped, curved flowers that resemble a Dutch pipe. Asarum L. is the scientific name for wild ginger,
while the scientific name for Hexastylis Raf. is heartleaf.
More than 100 taxa of Aristolochiaceae plants have been studied chemically, and many of these
are widely used in traditional medicine. The purpose of this chapter is to review the chemistry,
pharmacology, and clinical use of plants belonging to this family.
I. Asaroideae.
1. Sarumeae: Saruma.
2. Asareae: Asarum.
3. Bragantieae: Apama, Thottea.
Aristolochia L.
Asarum L.
Euglypha Chodat and Hassl.
Holostylis Duch.
Isotrema Raf.
Pararistolochia Hutch. and Dalziel
Saruma Oliv.
Thottea Rottb.
The Asarum genus occurs in Europe with 1 species, A. europaeum although 13 Aristolochia species
are listed.3 In the flora of tropical Africa, the genus Pararistolochia is reported along with Aristolo-
chia, the first being the predominant in the west countries (with 12 species),4 while in the eastern
regions of Africa, Aristolochia species are the most abundant and only Pararistolochia triactina
(Hook. f.) Hutch. and Dalz. is reported.5
In North America, the Aristolochiaceae family is present with three genera: Aristolochia L.
(Dutchman’s pipe), Asarum L. (wild ginger), and Hexastylis Raf. (heartleaf).6 The Aristolochia
genus predominates in South of America,7 although in Argentina, there are two classified Aristolo-
chiaceae genera: Euglypha Choda et Hassler and Aristolochia L.,8 and three in Brazil: Aristolochia
L., Euglypha Choda et Hassler, and Holostylis Duch.9
More than 100 Asarum species are known and about 30 species are distributed in Japan,10
where only 4 Aristolochia occur (A. kaempferi Willd., A. onoei Fr. et Sav., A. debilis Sieb. et Zucc.,
and A. contorta Bge).
China is certainly the country where Aristolochiaceae genera and species are well represented,
about 50 species of Aristolochia and 50 species of Asarum, along with a few other species of
Heterotropa, Saruma, and Thottea.11 Some species of Aristolochiaceae are also reported in
Australia.12
1- nitrogenated constituents:
phenanthrene derivatives
alkaloids
2- constituents without nitrogen:
terpenoids
lignoids
flavonoids
19.2.1.1.2 Alkaloids
All alkaloids isolated from Aristolochia spp. have an isoquinolinic nucleus and may be devided
into four groups (Figure 19.2):
Aporphinoids
Tetrahydroprotoberberine alkaloids
Benzylisoquinoline and bis-benzylisoquinoline alkaloids
Protopine
One of the most common aporphinic alkaloids that occur in many Aristolochia spp. is magno-
florine which is structurally and phylogenetically related to aristolochic acid derivatives18; it is a
quaternary ammonium base with hypotensive activity.25-26 Other aporphine alkaloids isolated from
Aristolochia plants are corituberine, with a formula consistent with magnoflorine but with a tertiary
nitrogen (from A. clematitis L.),18 (-)-N-acetylnornuciferine, isolated from A. bracteata Retz. (um-
galegel or erg-el-agrab is the popular Indian name),27 cepharadione-A, 4,5-dioxodehydroasimi-
lobine, and aristolodione obtained from the aerial parts of Aristolochia chilensis Miers. (vernacular
name oreja de zorro or hierba de la virgen),28 tuberosinone and its derivatives, isolated and identified
from A. tuberosa C. F. Liong et S. M. Hwang,29 and N-formylnornantenine and its 6a,7-dehydro
derivative from A. brevipens Benth. rhizomes.30 Recently, two other alkaloids have been isolated
and identified from Aristolochia triangularis Cham. et Schletch. roots (mil hombres is its trivial
name) named triangularine A and triangularine B.31
Among the tetrahydroprotoberberine alkaloids, cyclanoline represents the only one extracted
for the first time from A. debilis Sieb. et Zucc.,32 while ten 8-benzylberberine-type alkaloids were
extracted from A. gigantea (Hook.) Klotzsch, eight of which are glycosidic derivatives.33 A novel
(-)-8b-(4¢-hydroxybenzyl)-2,3-dimethoxyberbin-10-ol was isolated from aerial parts of A. constricta
Mutis ex H. B. K. along with new protopine-type alkaloids 3,5-di-O-methylconstrictosine, 5,6-
dihydro-3,5-di-O-methylconstrictosine, 5,6-dihydroconstrictosine, constrictosine, and 3-O-methyl-
constrictosine. All the protopine derivatives significantly reduce, in a dose dependent manner, the
electrical, acetylcholine, and histamine contractions of the isolated guinea-pig ileum.34
Bis-benzylisoquinoline alkaloids (11,12¢-linked 1-benzyltetrahydroisoquinoline dimer) appear
to be rare in Aristolochia species. The first isolated was (-)-curine from A. indica L., then tetrandrine
from roots of A. debilis Sieb. and Zucc., (-)-temuconine was obtained from A. elegans of Egyptian
origin, then (-)-pampulhamine, (-)-geraldoamine, (-)-pedroamine (alkaloids with one diphenyl ether
link between rings C and C¢) were isolated from defatted leaves of A. gigantea Mart.,18 along with
the recently isolated alkaloids of this type, named dimethylgrisabine, O-methyldauricine, from the
bark of A. gigantea Mart.35
19.2.1.2.2 Lignoids
From the chemical point of view, members of the Aristolochiaceae are known by their ability
to synthesize phenanthrene alkaloids and arylpropanoids. The latter include lignans and neolig-
nans. Such lignoids are reported to possess antitumor, antifungal, antibacterial, and insecticide
properties.62
Eupomatenoids are 3-methyl-2-phenyl-5(E)-propenylbenzofuran derivatives that fall within the
general chemical class of lignans and, more specifically, have been proposed as neolignans. They
owe their name to the family of Eupomatiaceae that is a rich source of these compounds. (±)-
Licarin A (or dehydrodiisoeugenol), (–)-licarin B (or eupomatenoid-8), eupomatenoid-7, and eupo-
matenoid-1 were isolated from roots and stems of plants of the Aristolochia genus (A. maxima L.
or A. taliscana Hook. and Arn.), popularly known as guaco or raiz de guaco in Mexican folk
medicine.63-64 Also, 7 lignoids 1 to 7 were also isolated and identified from A. birostris Duchtre, a
plant used in Brazilian folk medicine (common name capivara or angelicó or jarrinha).65
From seven Brazilian Aristolochia species (A. brasiliensis Mart. et Zucc., A. cymbifera Mart.
et Zucc., A. esperanzae Kuntz., A. triangularis Cham. et Schletch., A. birostris Duchtre, and A.
galeata Mart. et Zucc.) and from A. indica L. were isolated many dibenzylbutyrolactone type lignans.
Among these constituents, the formulas of cubebin and hinokinin56,58,62,65-67 are listed in Figure 19.5.
The 2,5-diaryl-3,4-dimethyltetrahydrofuranoids are a group of lignans found mainly among
members of the botanical families belonging to the order Magnoliales and were also found in the
botanically related family Aristolochiaceae. (+)-Zuonin-A, (+)-aristolignin, and nectandrin-B are
three examples of these tetrasubstituted tetrahydrofuran derivatives isolated from roots of A. chil-
ensis Miers., A. ponticum, and A. birostris Duchtre.19,65,68,69 These lignan type constituents were
described only in the Aristolochia species whereas neolignans, structurally related to asatone, were
also isolated from the Asarum and Heterotropa species.62
Another class of lignans that also occurred in many Brazilian Aristolochiae were the furofuran
type lignans: where asarinin and fargesin18,56 represented two examples of these compounds.
The 4-aryltetralones are a small group of lignans found previously in Virola sebifera (Myris-
ticaceae) and in Schisandra spp. (Schisandraceae). (-)-Aristotetralone was obtained as a minor
component in A. chilensis Miers.70,71 Figure 19.5 shows the main lignoid structures isolated from
Aristolochia species source.
19.2.1.2.3 Flavonoids
Only few flavonoids were reported from leaves, stems, roots, or rhizomes of the Aristolochiaceae
species: isorhamnetin-3-O-b-D-robinobioside,72 kaempferol-3-O-b-D-robinobioside,73 rutin, quer-
cetin-3-b-glucoside (quercitrin), isorhamnetin, and 3,3¢,4¢,6,8-pentahydroxyflavone18.
From the extracts of the roots of A. indica L. was reported the isolation and characterization
of a new naphtoquinone, aristolindiquinone.74 Chemical structures of these compounds are reported
in Figure 19.4.
31 Asarum species in China, divided into two subgenera, Asarum and Heterotropa.76,77 Hitherto,
the systematic classification of this genus resulted were debatable.
The chemical composition of the essential oils obtained from many Asarum species were
investigated by gas chromatography–mass spectroscopy (GC–MS) to identify the bioactive com-
pounds responsible for the local anaesthetic, analgesic, antipyretic, sedative, and hypotensive
activity proved in the popular medicine of other countries. So 1,8-cineole, asaricin, methyleugenol,
croweacin, b-pinene, a-thujene, myrcene, terpinen-4-ol, a-terpineol, safrole, and myristicin were
identified in A. sieboldii Miq. (common name Huaxixin), while from four Chinese medicinal
species, A. siebolii var. soeulensis Nakai, A. forbesii Maxim., A. inflatum, C.Y. Chen and C. S.
Yang, A. magnificum var. dinghugense, C.Y. Chen and C. S. Yang, and A. caudigerum Hance var.
cardiophyllum, 3,5-dimethoxytoluene, safrole, methyleugenol, elemicin, and 2-undecane were
found in all species, together with several mono and sesquiterpenes.25,75
The fragrant volatile oils of Asarum canadense L. (common name Canada snakeroot, wild
ginger), obtained from the pentane extract was subjected successively to stem distillation,78 con-
tained monoterpene hydrocarbons, alcohols and esters, aromatic compounds, such as linalool,
geraniol, a-terpineol, eugenol and methyl eugenol,79 and the sesquiterpene ketone, aristolone.80,81
Asatone, a neolignan compound, was isolated in many species of Heterotropa,110 while new neo-
sesquilignans, a heterotropanone, and a sesquiterpene, heterocurvistone, were isolated from H. takaoi
F. Maek.122-124 and H. curvistigma F. Maek., respectively.125
Many of the swallowtail species (Papilionidae, Lepidoptera) are associated either with Rutaceae
or Aristolochiaceae. Two papilionid butterflies, Luehdorfia puziloi and Luehdorfia japonica are
regarded as sibling species, but a distinctive characteristic between the two species is manifested
by the difference in host plants. Luehdorfia japonica feeds on a large variety of Heterotropa plants
and is also able to perform well on other aristolochiaceous plants such as Asiasarum or Asarum.
In contrast, Luehdorfia puziloi is restricted to Asiasarum plants. A feeding deterrent against larvae
of a papilionid butterfly Luehdorfia puziloi was isolated from Heterotropa aspera. One of the
antifeedant agents was identified as a neolignan compound, asatone.126 From the leaves of the same
host plant was isolated an oviposition stimulant component of Luehdorfia japonica and identified
as isorhamnetin 3-O-b-glucosil-(1fi 6)-b-galactoside-7-O-b-glucoside.127
• Madouling (fructus) referred to the ripe fruit of Aristolochia contorta Bge. or A. debilis
Sieb. et Zucc. and used in the treatment of respiratory diseases as an antitussive and anti-
asthmatic.
• Tianxianteng (herba) is the dried aerial part of A. contorta Bge. or A. debilis Sieb. et
Zucc. used as a diuretic against edema and as an antirheumatic.
• Qingmuxiang (radix) constituted by roots of A. contorta Bge. or A. debilis Sieb. et Zucc.,
therapeutically prescribed in diarrhea owing to enteritis, rheumatoid arthritis, hyperten-
sion, eczema, and snake bite.
• Guangfangji (radix) is the dry root of A. fangchi Y. C. Wu ex L. D. Chou et S. M. Hwang
used as antirheumatic and diuretic.
• Guanmutong (caulis) referred to dry vine of A. manshuriensis Kom., used as a diuretic
and antiphlogistic for treatment of edema and rheumatic arthralgia, eczema, and hyper-
tension.25,78
Besides these official species, several other Aristolochia spp. used in traditional medicine were
investigated pharmacologically. The biological activities of aristolochic acids were studied exhaus-
tively also.
19.3.1.1 Pharmacology
Aristolochia grandiflora Sw
Used in Mexican traditional medicine as an uterotonic, cytotossic, and antimicrobial agent, and to treat snakebites 36
Asarum heterotropoides Fr. Schmidt var. mandshuricum Kitag (manchurian wild ginger)
Antipyretic, analgesic, sedative, and hypotensive activity100,164,210
Asarum sagittarioides
Showed strong antihistaminic activity; amide is the active principle and it is proved to be an anti-allergic substance 114
Refined fluid extract of Qingmuxiang in tablets (each tablet corresponding to 6 g of the herb, dosage
of 4 to 12 tablets 3 to 4 times daily) was effective in stage II hypertension, particularly for the
systolic pressure, but it was ineffective in stage III hypertension. In 50 cases treated with fluid
extract of the herb, diastolic pressure was lowered by than 20 mmHg in 20 cases.139 The Aristolochia
mixture (Fructus Aristolochiae) was effective in treatment of 94 cases of chronic bronchitis; the
sputum became thin and was easily expectorated.
Analgesic effect was achieved with tincture or powder of A. contorta Bge. root for pain owing
to peptic ulcer, gastritis, gastric spasm, or gastric pain of other etiologies.139
Many Aristolochia spp. were used in traditional medicine for dermatological purposes. Skin care
products containing biological stimulators such as human placental extracts and optionally with
Aristolochia spp. extracts in polyethylene glycol (mol. wt. 1500) are effective against oversize
pores, pustules, acne, sunburn and its peeling, and are not irritating. The placental/Aristolochia
extracts are used in a ratio of 1:10 to 20.152
Aristolochia argentina Gris. was used in the treatment of pruritus,153 but argentilactone, a new
rhizome’s constituent, showed a skin irritant action. Several plants of the Aristolochia genus,
popularly known as guaco or raiz de guaco, according to Mexican folk medicine, were used in the
treatment of dermatological affections. The active components were four closely related compounds
of the lignan type (eupomatenoids): (±)-licarin A, (-)-licarin B, eupomatenoid-7 and eupomatenoid-
1.64 In Europe, A. clematitis L. was used not only for its emmenagogue and febrifugal properties,
but also for its cicatrizing activity (in the treatment of wounds with poor healing tendency, leg
ulcers, fistulae, foruncolisis, and refractory acne), although there was a report that this species was
an irritant.154 The isolation of AA-I from A. clematitis L. and the recognition of its mechanism of
action as a stimulant of phagocytosis activity made it possible to use this substance to enhance the
defense capacity of the body. Little result was seen in acute pyodermas and leg-ulcers.155 Tardolyt®
was used with good results by itself or in combination, in cases of pyodermia, deep folliculitis,
sweat gland abscesses, fistulae, and varicose crural ulcers.156
A. fangchi Y. C. Wu ex L. D. Chou et S.M. Hwang, A. moupinensis Franch. and A. tagala
Champ. were used in Chinese folk medicine in the treatment of eczema,25 and A. baetica L. and
A. longa L. were used as warts and dermatitis remedies, respectively.157
Dried A. debilis Sieb. et Zucc. extracted with alcohol or with a mixture of water and alcohol
may be used for the preparation of lotions such as hair growth stimulants and therapeutics for
prostate gland disease.158
19.3.2.1 Pharmacology
The main use of Xixin in Chinese medicine was as headache and cough remedy. The decoction of
1 to 3 g of vegetal material may be given per os. In toothache and gengivitis, it was applied as a
locally patent medicine, Yatongshui®, a toothache liquid containing Herba Asari and other plant
material. Xixin also provided an anaesthetic effect that is useful in tooth extraction.
A 3 percent volatile oil of Xixin was used as a local infiltrative anesthesia and nerve blocker
in 33 cases of otorhinolaryngological and ophthalmic operation with good effect in 33 cases,
relatively good effect (occasional local pain) in 17 cases, and no effect in 2 cases.139
Many pharmaceutical preparations containig trans-isoasarone were formulated, Escarol® having
bronchospasmolytic, secretolytic, and antibacterial properties. This active compound was isolated
from Asarum europaeum L. roots. Of note are three forms of application: tinctura rhizomae Asari
recentis, dragees with dry extract, and tablets with the isolated effective substance. The Rhizoma
Asari europaei drug is noted also as an emetic remedy.165-168
Asarum spp. also found wide applications in folk medicine for dermatologic purposes. Asarum
enters in the formulation of antibacterial, low-irritation cosmetics along with N-long chain acyl
basic amino acid derivatives and their salts and/or polyhydric alcohols with their alkyl ester. Plant
extracts synergistically enhanced the antibacterial activiy of these chemical compounds.169,170
Asarum extracts (10 to 20 ml/100 kg) entered in facecare soap composition for treating acne along
with soap in 95 to 97 parts, essence of 1 to 2 percent, and powdered Chinese medicine (120 mesh)
in 1 to 3 parts.171
Asarum heterotropoides F. Schmidt forms part of a tincture formulated for treating scar together
with many other plant extracts,172 while a hair tonic was prepared from Asarum sieboldii Miq. or
Asarum heterotropoides F. Schmidt. Plant material (1 kg) was extracted with 95 percent of ethanol
(5 l) and water (5 l) for 4 days to give a macerate that was mixed with menthol 0.2, perfume 0.3,
95 percent ethanol 48 and water 48.5 parts to give a satisfactory hair tonic.173
A. canadense L. are the source of the perfumery raw material known as wild ginger oil. No
irritancy, allergenicity, nor phototoxicity on application to the skin of various animals, including
man, could be demonstrated.174 The leaves can cause dermatitis in some humans.175
19.4 ACKNOWLEDGMENTS
I wish to express my special thanks to Prof. G. G. Leitao (Nucleo de Pesquisas de Produtos Naturais,
Universidade Federal do Rio de Janeiro, Brazil) for the useful material provided in this work. I am
also grateful to Prof. C. Vosa and Dr. A. Costa for their botanical advice (Department of Botanical
Science, University of Pisa). I wish to thank Dr. Laura Pistelli, Dr. A. Bertoli, and Dr. F. Morganti
for their technical assistance throughout this work.
CONTENTS
20.1 Introduction
20.2 Paratecoma
20.3 Tabebuia
20.4 Tecoma
20.5 Jacaranda
20.6 Campsis
20.7 Catalpa
20.8 Conclusions
20.9 References
20.1 INTRODUCTION
The Bignoniaceae (Scrophulariales) family consists of trees, shrubs, often climbers or twiners, or
very rarely, herbaceous plants. The family is found chiefly in the tropics, especially in the tropical
part of South America, and includes about 120 genera and 700 to 750 species.1 Some of the genera
that are vines include Podranea, Pandorea, Tecomanthe, Doxantha, Pithecoctenium, Phaedranthus,
Pyrostegia, Clytostoma, Campsis, Pseudocalymma, Distictis, and Anemopaegma. Examples of
shrubs include Tecomaria, Stenolobium, and Tecomella, while the tree members include Catalpa,
Crescentia, Jacaranda, Radermachera, Oroxylum, Millingtonia, Dolichandrone, Spathodea,
Markhamia, Newbouldia, Stereospermum, Heterophragma, Kigelia, Parmentiera, Tabebuia, and
Godmania.
The leaves of family members are opposite and decussate, rarely alternate, simple or mostly
pinnately compound with the terminal leaflet sometimes tenderil-like; stipules absent; inflorescence
a panicle or raceme or cyme; flowers bisexual, zygomorphic, often showy; calyx generally with 5
lobes, campanulate; corolla with 5 lobes, sometimes bilabiate, campanulate, or funnelform, imbri-
cate; stamens 5, but often only 4 or 2 perfect, the others staminodes, alternate with the lobes of
the corolla; anthers 2-locular, dehiscing longitudinally, distinct or more usually connivent in pairs;
disk usually present, hypogynous; pistil 1; carpels 2; ovary superior, 2-locular; style simple and
terminal; stigma 2 lobed; placenta axile and bilocular or unilocular with 2 parietal bifid placentas;
ovules numerous; fruit a capsule; seeds often winged; embryo straight; endosperm absent.
Several species are extensively cultivated for their horticultural value and some yield useful
timber. The timber species include Tabebuia (the West Indian boxwood), the Catalpa of North
America, Paulownia from China, Kigelia pinnata of West tropical Africa, Stereospermum
kunthianum, and Newbouldia laevis. Many species have local medicinal uses. The unripe fruits of
Kigelia pinnata are used to treat syphilis and rheumatism, and pieces of the fruit rubbed on the
breast of mothers are used to increase the supply of milk. The pods of Stereospermum kunthianum
20.2 PARATECOMA
Paratecoma peroba Kuhlm. (syn. Tecoma peroba) is a native of Brazil. The valuable timber is
exported to Europe and elsewhere. Because the timber of Aspidosperma polyneuron is superficially
similar, the latter is known as Peroba rosa. The wood has also been misnamed Illipa or Bassia.
This wood is among the six most commonly causing dermatitis in France.8 Early accounts of
dermatitis from this species are those of Touraine et al.,9 and Touraine and Gole.10 Barnett11
described the extensive dermatitis caused by the sawdust, involving the hands, face, and neck, and
sometimes axillae and groins. Paratecoma was shown to contain lapachol, lapachone, and an
alkaloid. In patients with dermatitis, patch tests incriminated lapachone (lapachenole) as the sen-
sitizer; lapachol was present only in small amounts.12
20.3 TABEBUIA
About 100 species are distributed over an area ranging from Mexico to northern Argentina, including
the West Indies. Many species provide valuable timber, and many of them, perhaps all, can cause
dermatitis owing to the lapachol, deoxylapachol, and lapachone content of their wood.5 The woods
of these species, which were formerly often named Tecoma, can also cause conjunctivitis and
respiratory symptoms13 and constitutional symptoms.14
Table 20.1 shows the occurrence of lapachol, deoxylapachol, and lapachone derivatives in
several of these species and in some other members of the family. These compounds occur
predominantly in the wood. Some of these quinoid compounds have antitumor, antibacterial, or
antifungal properties.15-18 From the leaves and flowers of this species were reported the presence
of flavonoids19-24 and from the stem and rootbark, iridoid, phenylpropanoid, and benzenoid com-
pounds were reported.25-28
20.4 TECOMA
There are 16 species in the region between Florida and Argentina. Some produce useful timber
while others are used as a source of tecomin, a yellow dye, which turns red in alkaline solution.
Several species, for example, T. avellanedae, T. pentaphylla, and T. serratifolia were reported to
produce dermatitis, respiratory, and constitutional symptoms, and now have been transferred to the
genus Tabebuia.
20.5 JACARANDA
There are about 50 species in Central and South America and the West Indies. Many of these trees
and shrubs are highly ornamental and are cultivated where conditions are suitable. The wood of
J. chelonia is used in cabinetmaking. According to Woods and Calnan,29 the use of Jacaranda as
a genus name has often been confused with jacaranda, the popular common name for several species
of Dalbergia and Machaerium of the Leguminoseae family. It is therefore impossible to interpret
many case reports of dermatitis, in which the responsible species has not been botanically identified.
It is probable that in such reports species of Dalbergia were responsible because some of them are
potent sensitizers. However, some of the Jacaranda species that have been implicated include
J. braziliensis, J. acutifolia, and J. ovalifolia.30
The quinoid, jacaranone, has been isolated from the leaves of several species of Jacaranda.31-34
This compound was found to have antitumor activity.35,36 Other compounds isolated from the leaves
and stem of plants of this species were triterpenes.31,35,37–39 The flowers contained flavonoids.19,40,41
20.7 CATALPA
This genus contains 11 species of trees native to East Africa and to North and South America.
Several species are extensively cultivated for their horticultural value, and some yield a useful
timber. Catalpa speciosa Warder commonly known as western catalpa or catawba tree, native from
Illinois to Arkansas, a tree to 100 ft high or more, is planted in Hawaii for reforestation. The
common catalpa, Indian bean (C. bignonioides Walt.), from the southeastern United States, is a
smaller tree cultivated for the beauty of its flowers. The flowers of various species of Catalpa have
been suspected to cause dermatitis.42,56,57
Iridoids, phenylpropanoids, flavonoids, and the steroid, sitosterol have been isolated from C.
bignonioides.58-61 The leaves of C. speciosa were also found to contain iridoids.62-66
20.8 CONCLUSIONS
Plant-induced dermatitis, like an allergy, is dependent on a previous sensitivity of the individual.
The degree of poisoning may vary from minor or temporary skin irritation to very painful inflam-
mation with blisters persisting for weeks and possibly requiring hospitalization. The severity of
dermatitis produced by plants in the Bignoniaceae depends on the plant contacted, the degree of
contact, and the relative susceptibility of the individual. Although only a few species of the
Bignoniaceae have been reported to induce dermatitis, more species may be able to do so, but have
not been tested for this ability.
CONTENTS
21.1 Introduction
21.2 Botanical Aspects
21.2.1 Classification
21.2.2 The Body
21.2.2.1 Biology
21.2.3 Distribution
21.3 Biochemistry of Bromeliaceae
21.3.1 Biochemistry of Pineapple
21.3.2 Bromelain
21.3.3 Other Proteolytic Proteinases from Pineapple
21.3.4 Proteolytic Enzymes in Other Species of Bromeliaeae
21.4 Pathology Induced by Pineapple and Bromelain
21.4.1 Allergic Reactions to Bromelain
21.4.2 Mechanisms in Allergic Skin Diseases
21.5 Clinical and Experimental Application of Bromelain
21.6 Traditional Uses of Bromeliaceae
21.7 Acknowledgments
21.8 References
21.1 INTRODUCTION
Bromeliads are members of a large family of plants (Bromeliaceae). The best known member is
the edible pineapple (Table 21.1). The Bromeliaceae family is exclusive to America where almost
2500 species are found. The only exception is Pitcairnia feliciana of Africa. Bromeliads are found
from Virginia in the United States to southern Argentina. There are certain regions of the world
with a large variety of species such as Mexico, the Antilles, Costa Rica, eastern and southern Brazil,
the Andes of Colombia, Peru, and Chile.
During the explorations of Columbus, Americo Vespucci, Oviedo, and Portuguese explorers,
the first bromeliad, Ananas (whose name come from the Brazilian Guarani Indian word “Anana”)
was taken to Europe and then carried around the world. Ananas flourished in almost every tropical
country as in India, Java, Sumatra, and the Philippines. Oviedo represented the pineapple in his
Historia General de las Indias published in 1535.1 Rumph was the first botanist to describe it
(Figure 21.1).
Pseudananas sagenarius Gravatá de cerca, gravatá de (Arruda da Camara) Camargo rede, y vira
Ananas ananasoides Ananas de ramosa, curibujil, (Baker) L. B Smith maya, piñon, piñuela
Ananas nanus (L. B. Smith) Ananaí L. B. Smith
Ananas parguazensis Gravatá, piña montañera. Camargo and L. B. Smith
Ananas lucidus Miller Curagua, curaná, curauá, kulaiwat
Ananas bracteatus (Lindley) Ananas bravo, ananas do mato (Schultes f.)
Ananas fritzmuelleri Camargo Ananas silvestre, gravatá de cerca
Ananas comous (L) Merril Abacaxi, ananas, piña
FIGURE 21.1 The earliest pineapple drawing from Oviedo’s Historia General y Natural de las Indias.1
1. Root system only as a support in epiphytic species. This can disappear in mature plants.
2. Rosette leaves, generally with reduced stems.
3. Trichomes (hairs or scales) on the surface that absorb water and nutrients.
4. Terminal inflorescence supported by a scape with coloring bracts.
5. Flowers in series of three tepals: three sepals, three petals, six stamens, and three carpels.
They are generally hermaphroditic.
6. Fruits are capsules or berries.
7. Apiculate seeds or with a coma basal or apical.
These characters have been used traditionally in the classification of the family (Figure 21.2).
Some other, like stigma form, are useful in some taxa.14
Most epiphytic bromeliads grow in median altitudes between 1500 and 2500 m. However, terrestrial
bromeliads are found as high as 4000 m. The distribution of the family north and south of the
equator indicates that plants receive rainfall at differing times of the year.
Bromeliads are generally pollinized by birds, but bats, bees, and butterflies also have been
observed visiting flowers.
In cultivation, hybrids are produced, but some studies have been made with regard to hybrid
formation in nature.
21.2.3 DISTRIBUTION
Seeds are dispersed by wind, but in bromelioideae seeds are dispersed by animals. There are a
variety of living forms associated with aquatic bromeliads that accumulate water in the base of
leaves.
Some genera are dioecious (e.g., they have male and female reproductive parts on separate
plants).
Bromeliaceae can be described in ecological terms as a group of stress-tolerant tropical herbs
with a pronounced tendency toward epiphytism and saxicoly. Whether supported by rock, soil, or
a host, a large majority of the species prefer habitats characterized by at least one major physical
restraint. Light, water, or mineral nutrients, or some combination of these commodities, is in short
supply (or much less commonly in excess) at least part of each year.13
Pike et al.65 did experimental work using rabbits and found antibody to rye grass (Lolium
perennis) cross-reacted with bromelain and vice versa. Deglycosylation of the proteases showed
that cross-reactions were based on recognition of the carbohydrate moiety of the allergen indicating
21.7 ACKNOWLEDGMENTS
We would like to thank Freddy Leal, Shinkichi Tawata, and A. E. Duane Bartholomew for their
valuable information. We thank Miss Odeth Santos Brown and Miss Oralia Aragón Miranda for
their skillful help with the manuscript.
This manuscript was prepared with the support of CONACyT (México) No. 2307P-N9508 and
PAPPIT University of México No. IN201095.
21.8 REFERENCES
1. Oviedo, F., Historia General y Natural de las Indias. Vol. 5, Ed. Atlas, Madrid, 1535.
2. Smith, L. B. and Downs, R. J., Pitcairnioideae (Bromeliaceae), Flora Neotropica, Hafner Press, New
York, Monogr. 14, 1, 1974.
3. Smith, L. B. and Downs, R. J., Tillandsioideae (Bromeliaceae), Flora Neotropica, Hafner Press, New
York, Monogr. 14, 563, 1974.
4. Smith, L. B. and Downs, R. J., Bromelioideae (Bromeliaceae), Flora Neotropica, Hafner Press, New
York, Monogr. 14, 1493, 1979.
5. Gilmartin, A. J., Bromeliaceae of Ecuador, Monograph Phanerogamarum, 4, Vol. No. 1, Cramer, J.,
Ed., Lehre, Germany, 1972.
6. Rauh, W., Bromeliads for Home, Garden and Greenhouse, Blandford Press, 1979, 431.
7. Ritcher, W., Zimmerpflanzen von heute and morgen, Bromeliaceen, Newman, J., Ed., Leipzig, 1965,
438.
8. Gardner, C. S., A Systematic Study of Tillandsia subgenus Tillandsia, Ph.D. dissertation. Texas A &
M University, 1982, 305.
9. Utley, J., A revision of middle American Tecophylloid Vrieseas (Bromeliaceae). Stud. Zool. Bot.
(Tulane), 24, 1,
10. Utley, J., Bromeliaceae, in Flora Mesoamericana, Alismateceae a Cyperaceae, Vol. 6, Universidad
Nacional Autonoma de México, Mexico, 1994, 89.
11. Matuda, E., Las Bromeliáceas de Chiapas, Anales Int. Biol. Univ. Nac. México, 23, 85, 1992.
12. Matuda, E., Las Bromeliáceas, in Flora del Estado de México, Tomo III, Biblioteca Enciclopédica
del Estado de México, Mexico, 1979.
13. Benzing, D. H., The Biology of Bromeliads, Mad River Press, 1983, 305.
14. Brown, G. L. and Gilmartin, A. J., Stigma structure and variation in Bromeliaceae, Neglected Taxo-
nomic Characters, Brittonia, 36, 363, 1984.
15. Leal, F. and Coppens d’Eeckenbrugge, G., in Pineapple, Fruit Breeding, Janick, J. and Mooore,
J. N., Eds., 1996, Chapter 9.
16. Flath, R. A., Pineapple, in Tropical and Subtropical Fruits: Composition, Properties and Uses, Nagy,
S. and Shaw, P. E., Eds., Avi, Westport, CT, 1980.
17. Py, C., Lacoeuilhe, J. J., and Teisson, C., L’Ananas, sa Culture, ses Produits, Mainsonneuve and
Larose, Paris, 1984.
18. Morton, J. F., Fruits of Warm Climates, Media Inc., Greensboro, NC, 1987.
19. Gortner, W. A. and Singleton, V. L., Chemical and physical development of pineapple fruit, III:
nitrogenous and enzyme constituents, J. Food Sci., 30, 24, 1995.
20. Leal, F., On the history, origin and taxonomy of the pineapple, Interciencia, 14, 235, 1989.
21. Collins, J. L., Pineapples in ancient America, Sci. Mon., 67, 372, 1948.
22. Ohta, H., Kinjo, S., and Osajima, Y., Glass capillary gas chromatographic analysis of volatile com-
ponents of canned Philippine pineapple juice, J. Chromatogr., 409, 409, 1987.
23. Tawata, S., Taira, S., Kobamoto, N., Zhu, J., Ishihara, M., and Toyama, S., Synthesis and antifungal
activity of cinnamic acid esters, Biosci. Biochem., 60, 909, 1995.
CONTENTS
22.1 Introduction
22.1.1 History
22.1.2 Lichens
22.1.3 Medicinal Use
22.1.4 Economic Uses of Lichens
22.2 Chemistry
22.2.1 Atranorin
22.2.2 Usnic Acid
22.2.3 Evernic Acid
22.2.4 Other Lichen Acids
22.3 Clinical Effect
22.3.1 Contact Dermatitis
22.3.2 Immediate Hypersensitivity Reactions
22.3.3 Photosensitising Ability
22.3.4 Cross Reactions
22.3.5 Individual Case Reports
22.3.6 Patch Testing
22.4 References
22.1 INTRODUCTION
22.1.1 HISTORY
Theophrastus used the term lichen (derived from the Greek leprous) to describe a superficial growth
on the bark of olive trees. Initially, lichens also included the liverworts (Hepaticae), but Diocorides
ascribed the term to true lichens on account of their resemblance to the cutaneous disease (pre-
sumably lichen planus) for which they were supposed to be specific.
Lichens were first formally segregated botanically in 1694 by Tourneforte although it was in
1868 when the concept of a compound organism living in symbiosis was advanced by Schwendener.
Lichens are now classified in the phylum Mycophycophyta in the kingdom Fungi.
22.1.2 LICHENS
Lichens are dual organisms composed of a symbiotic relationship between an alga and a fungus.
The fungus, usually an Ascomycete, provides the plant its shape, and the alga provides the ability
to photosynthesis. This successful combination is able to produce a more elaborate and durable
22.2 CHEMISTRY
Compared with common sensitizers of occupational and environmental importance, lichens are of
minor significance only. The sensitizing genera of lichens include Parmelia, Evernia, Cladonia, and
Usnea although Alectoria, Cetraria, Lecanora, and Xanthoria species have also been reported to be
allergenic (see Table 22.1). The allergens are largely the so-called lichen acids that include atranorin,
usnic acid, evernic acid, petaloric acid, and fumarprotocetraric acid.9-14 Lichens acids are generally
produced by the fungal component of the lichen.15,16
22.2.1 ATRANORIN
Atranorin was first extracted in 1877 from Lecanora atra, which gave it its name. A number of
studies11,14-30 have demonstrated the allergenic potential of atranorin. Using the guinea pig
maximisation test, Sandberg and Thune28 were able to sensitize 30 percent of test animals, which
corresponds to a moderate allergenic capacity (grade III). It is unclear whether atranorin is also
a photosensitizer receiving negative results from phototesting by Sandberg and Thune28 but
positive results by others.12,13,31,34
22.4 REFERENCES
1. Gilbert, O. L., Lichens as indicators of air pollution in the Tyne Valley, in Ecology and the Industrial
Society, Goodman, G. T., et al., Eds., Blackwell, Oxford, 1965, 35.
2. Ainsworth, G. C., Ainsworth and Bisby’s Dictionary of the Fungi, 6th ed, Kew, Commonwealth
Mycological Institute, 1971.
3. Ahmadjian, V., A guide to the algae occurring as lichen symbionts: isolation, culture, cultural phys-
iology and identification, Phycologia, 6, 127, 1967.
4. Bylicka, H., Antibiotics of lichens, Acta Microbiol. Polon., 1, 185, 1952.
5. Kerry-Nicholls, J. H., The origin, physical characteristics, and manners and customs of the Maori
race, from data derived during a recent exploration of the King Country, New Zealand, J. R. Anthrop.
Inst., 15, 187, 1886.
6. Shibata, S., Relation between chemical constitution and antibacterial effects, of usnic acid and its
derivatives, J. Pharm. Soc. Jpn., 68, 298, 1948.
7. Perez-Llano, G. A., Lichens. Their biological and economic significance, Bot. Rev., 10, 1, 1944.
8. Arctander, S., Perfume and Flavor Materials of Natural Origin, Published by the author, Elizabeth,
NJ, 1960.
9. Lovell, C. R., Plants and the Skin, Blackwell Scientific Publications, Oxford, 1993.
10. Mitchell, J. C. and Maibach, H. I., Sensitizing capacity of usnic acid derived from lichenized fungi,
Acta Derm. Venereol., 49, 498, 1969.
11. Mitchell, J. C. and Shibata, S., Immunologic activity of some substances derived from lichenized
fungi, J. Invest. Dermatol., 52, 517, 1969.
12. Thune, P., Allergy to lichens with photosensitivity, Contact Derm., 3, 213, 1977.
13. Thune, P. and Solberg, Y. J., Photosensitivity and allergy to aromatic lichen acids, Compositae
oleoresins and other plant substances, Contact Derm., 6, 64, 1980.
14. Thune, P., Solberg, Y., McFadden, N., Staerfelt, F., and Sandberg, M., Perfume allergy due to oak
moss and other lichens, Contact Derm., 8, 396, 1982.
15. Asahina, Y. and Shibata, S., Chemistry of Lichen Substances, Japanese Society Promotion of Science,
Tokyo, 1954.
16. Culberson, C. F., Chemical and Botanical Guide to Lichen Products, Chapel Hill, University of North
Carolina Press, 1969.
17. Dahlquist, I. and Fregert, S., Atranorin and oak moss contact allergy, Contact Derm., 7, 168, 1981.
18. Gonçalo, S., Contact sensitivity to lichens and Compositae in Frullania dermatitis, Contact Derm.,
16, 84, 1987.
19. Gonçalo, S., Cabral, F., and Gonçalo, M., Contact sensitivity to oak moss, Contact Derm., 19, 355, 1988.
20. Fernandez de Corres, L., Photosensitivity to oak moss, Contact Derm., 15, 118, 1986.
21. Fernandez de Corres, L., Leaniz Barrutia, I., Munoz, D., Bernaola, G., Fernandez, E., and Audicana,
M. T., Multiple sensitizations to plants in a farmer, Contact Derm., 17, 315, 1987.
22. Fregert, S. and Dahlquist, I., Patch testing with oak moss extract, Contact Derm., 9, 227, 1983.
CONTENTS
23.1 Introduction
23.1.1 Plant Family
23.1.1.1 Geographical Location
23.1.1.1.1 Subfamilies, Genera, and Species
23.2 Chemistry
23.2.1 General Chemistry of the Verbenaceae
23.2.1.1 Chemistry of Selected Species
23.3 Clinical Efffects
23.4 References
23.1 INTRODUCTION
23.1.1 PLANT FAMILY
The Verbena family is large, comprising more than 3000 species in 75 to 100 genera.1,2 It includes
herbs, shrubs, trees, lianas, and several thorny xerophytes, accounting for the distribution of the
family in dry regions.
Botanically, the Verbena family is characterized by usually opposite, rarely whorled or alternate,
leaves, entire or divided, that lack stipules. The flowers are bisexual and arranged in a cyme or a
raceme. The calyx is four- or five-lobed or toothed. The tubular corolla likewise is four- or five-
lobed. The fruit is either a drupe or, less commonly, a capsule, or dividing into two or four one-
seeded nutlets.1,3 The Verbenaceae are often hairy and characteristicallly the hairs are incrusted with
calcium carbonate and/or silicic acid.2 Glandular hairs, secreting essential oils, are also common.2
Though the distribution is worldwide, the majority of species is found in tropical, subtropical, and
also temperate regions in the southern hemisphere.2 The family belongs to the order Lamiales along
with Labiatae and others and though the Verbenaceae is largely woody, it is considered to be closely
related to the herbaceous Labiatae.1
23.1.1.1.1 Subfamilies, Genera, and Species
According to Hegnauer,2 the family is divided into eight subfamilies:
However, Hegnauer states that another source only includes the Viticoideae, Verbenoideae,
Caryopteroideae, and Nyctanthoideae in the Verbena family.
Important economic uses include among others timbers, essential oils, teas, herbal remedies,
and ornamentals.1 Timber-producing genera are Tectona (teak) from Southeast Asia, Citharexylum
(zither wood) from Mexico and South America used for musical instruments, Vitex celebica from
Southeast Asia, Petitia domingensis Jacq. (fiddle wood) from the West Indies, and Premna from
Malaya used by the Japanese for knife handles.1 Valuable oils are obtained from Vitex agnus-castus
(chaste tree) and Lippia citriodora (verveine odorante, lemon-scented Verbena). The latter yields
Verbena oil.5 The leaves of this and other Lippia species as well as some Lantana species are used
for tea in South America and West and South Africa. The most widely used herbal remedy of the
Verbenaceae is probably Verbena officinalis L. (vervain, wild verbena). Other important species in
that respect are Lippia dulcis (Yerba dulce) of Mexico and L. scaberrima of South Africa and L.
citriodora.6,7 Many genera are cultivated for ornamental purposes in tropical and subtropical
gardens, and in gardens of temperate regions species of Callicarpa, Caryopteris, Clerodendron
(equivalent to Clerodendrum), Vitex, and Verbena are found. Species of Clerodendron, Lippia, and
Lantana are also used as indoor plants.
Relatively few species of this large family have been reported to cause dermatitis of allergic,
irritant, or urticarial nature or other skin symptoms (Table 23.1). Some of the more important are
presented in the following.
Lantana camara L.—A woody, half-climbing, up to 6 ft high shrub with a variety of flower
colors and a strong unpleasant smell. Stems and leaves are covered with short hairs and are rough
to the touch.8 Some races of this plant are prickly.8 It is native to the tropical regions of America,
but is now found in tropical, subtropical, and warm-temperate parts of the world, cultivated as a
hedge or ornamental plant, including house plants or naturalized (Figure 23.1).3 It is the prinicipal
weed in 12 countries and a serious weed in 10.9 As indicated by some of its common names (Table
23.1), it is considered a serious pest, not only because of its rapid spread as a weed, but more so
because it is reported to be one of the 10 most toxic weeds in the world.9 The toxicosis caused by
livestock’s (cattle, buffalo, sheep, and goats) ingestion of lantana plants, the allelopathic effect of
the plant on neighboring vegetation including grasses, and the infestation thus diminishing the
potential pastures available are sources of economic losses.9
Lantana toxicity runs a three-phased course: the first is release and absorption of the toxins in
the gastrointestinal tract, followed by interaction between toxins and hepatocytes, closure of bile
canaliculi, and gall bladder paralysis resulting in cholestasis and hepatic injury. This leads to
hyperbilirubinemia and hyperphylloerythrinemia, phylloerythrin being a breakdown product of
chlorophyll.5 The third phase is the manifestation of the tissue damage caused by excessive amounts
of bilirubin and phylloerythrin and includes renal damage and inflammation, photochemical reac-
tions, and photosensitization of skin.9,10 Acute poisoning in animals leads to constipation, followed
by sedation and photosensitization in the next 24 to 48 h, reddening of the muzzle that together
with other hairless parts become swollen, conjunctivitis, and later severe, bloody gastroenteritis
and possibly death in 3 to 5 days.5,8-10 In chronic poisoning, photosensitization is a prominent
feature. Nonpigmented skin without hair is first affected, whereas black, hairy skin may never
become involved.8 The affected skin becomes yellow, swollen, and hard with painful cracking and
* This subfamily has been reclassified and now belongs to the family Avicenniaceae.4
peeling, leaving raw areas. The inflammation involves adjacent mucous membranes of mouth, nose,
and eye as well as eyeballs.8 The chronic poisoning in sheep results in significant reduction in both
cellular and humoral immunity and the nonspecific phagocytic activity of splenic reticulo-endot-
helial cells.11
Verbena venosa Gillies & Hooker, equivalent to Verbena rigida Sprengel—The Sotho use a
root decoction of the plants for heartburn and colic.12
Vitex littoralis A. Cunn., equivalent to Vitex lucens T. Kirk is native to New Zealand.18
23.2 CHEMISTRY
23.2.1 GENERAL CHEMISTRY OF THE VERBENACEAE
The most common compounds within the family are flavone glycosides, such as vitexin and
orientin.25 Other important compounds are iridoid glycosides, such as verbenalin, phenols and
phenolic acids, methylated 6- or 8-hydroxy flavonols, quinones, diterpenoids, and essential oils.2
recommended.22 Krogh20 showed that moistened teak dust was toxic when patch testing both patients
and controls, whereas native teak dust only elicited allergic reactions. However, patch testing with
teak wood dust or shavings generally should be avoided because the combined possible irritant and
allergic properties may make interpretation difficult.4,22
The termite and insect repellant activity is owing to tectoquinone (2-methy lanthraquinone)
and related anthraquinones and deoxylapachol.2,33 Probably lapachol, deoxylapachol, and other
naphthoquinones as well as dehydrotectol and other naphthol derivatives are also responsible for
the antifungal activity. Additionally, teak may contain 2-methoxytoluene, 2-iodobenzoic acid, n-
heptylamine, butyric acid, a cis 1-4 polyisophrene, tectol, and often has a high rubber content.2,20
Verbena hastata L.—The plant contains the iridoid glycosides verbenalin and hastatoside.2
Verbena officinalis L.—The first iridoid glycoside isolated was verbenalin in 1908, and in 1935
it was recognized as identical with the well-known cornin.2 Another iridoid glycoside, hastatoside,
was isolated in 1970 and aucubin in the 1980s.2 The major flavonoid compound is luteolin 7-
diglucuronide and other flavonoids are the 6-O-substituted aglycones sorbifolin (trihydroxy-5,6,4´-
methoxy-7 flavone), pedalitin (tetrahydroxy-5,6,3´,4´-methoxy-7-flavone), and nepetin (equivalent
to eupafolin) (tetrahydroxy-5,7,3´,4´-methoxy-6-flavone).40,41 Tomás-Barberán et al.25 detected the
6-hydroxyflavone glycosides 6-hydroxy luteolin and 6-hydroxyapigenin (scutellarein), and Reynaud
et al.42 isolated four O-glycosylflavonoids, namely luteolin 7-glucoside, apigenin 7-glucuronide,
pedalitin 6-glucoside, and apigenin 7-galactoside. In addition, verbascoside (acteoside), a phenolic
compound isolated from more species of the Verbenaceae, has been found in Verbena officinalis.43
The dried leaves contain caffeic acid.2 The allergen(s) are unknown, but potential candidates include
flavonoids and phenols.44
Verbena venosa Gillies & Hooker, equivalent to Verbena rigida Sprengel—The leaves contain
urease.12
Vitex littoralis A. Cunn., equivalent to Vitex lucens T. Kirk—The iridoid glucoside5 aucubin
and agnuside (equivalent to agnoside) have been isolated from the wood as well as the flavone-C-
glycosides vitexin (apigenin 8-C-glucoside), isovitexin (equivalent to saponaretin equivalent to
homovitexin equivalent to apigenin 6-C-glucoside), orientin (luteolin 8-C-glucoside), isoorientin
(luteolin 6-C-glucoside), and vicenin-2. The leaves contain p-hydroxybenzoic acid and stearic acid
and the bark contains wax alcohols such as ceryl alcohol and the phytosterol b-sitosterin.2
CONTENTS
24.1 Introduction
24.2 Cupressaceae
24.2.1 Calocedrus
24.2.2. Thuja
24.3 Boraginaceae
24.3.1. Cordia
24.4 Ebenaceae
24.4.1 Diospyros
24.5 Leguminosae
24.5.1 Leguminosae-Caesalpinioideae
24.5.2 Leguminosae-Mimosoideae
24.5.2.1. Acacia
24.5.3 Leguminoase-Papilionoideae
24.5.3.1 Brya
24.5.3.2 Bowdichia
24.5.3.3 Dalbergia
24.5.3.4 Machaerium
24.6 Malvaceae
24.6.1 Thespesia
24.7 Meliaceae
24.8 Moraceae
24.9 Proteaceae
24.10 Sterculiaceae
24.10.1 Mansonia
24.10.2 Tectona
24.11 References
24.1 INTRODUCTION
The action of woods to the human being might be as follows
According to the four types of allergic diseases, sensitizing species are found among commercial
timbers in the following order
Irritation and allergic hypersensitivity of the immediate type is caused by several species listed
in Table 24.1. Only in one species the responsible sensitizer, that in contrast to the other unknown
allergens is a low molecular substance, has been identified (see Thuja plicata).
Allergic contact dermatitis (type IV hypersensitivity) generally comes from the heartwood. The
sapwood seldom contains sensitizing compounds. The constituents responsible for allergic reactions
occur in about 20 different plant families (e.g., Leguminosae, Bignoniaceae, Anacardiaceae, Lau-
raceae, Ebenaceae, Moraceae, Pinaceae, and others) and comprise such different chemical groups
as benzo-, naphtho-, furano- and phenanthrene quinones, stilbenes, flavones, coumarins (oxidation
products of resin acids), terpenes, steroids, phorbols, tropolones, and other phenolic substances. In
nearly half of the species suspected to cause allergic contact dermatitis the sensitizing constituents
are still unknown, for example, in American mahogany, Afzelia, Padouk, Sapeli, Wengé, Panga-
panga, Imbuya, and East Indian Satinwood.
The following description concerns those wood species that cause allergic contact dermatitis
and contain sensitizing constituents that have been isolated and structurally identified up to date.
24.2 CUPRESSACEAE
The Cupressaceae family comprises 125 species in 20 genera.
24.2.1 CALOCEDRUS
Three species native to Siam, Burma, China, Formosa, and the Pacific coast of North America are
known in this genus.
Calocedrus decurrens (TORR.) FLORIN is commonly known as Incense cedar. This tree, native
to California and Oregon, is used for pencil manufacture, fence posts, boarding, venetian blinds,
chests, and toys. Two cases of contact dermatitis have been described by Calnan.22 In the first case,
a female clerk developed dermatitis of the right hand, middle and ring finger, later spreading to
the arm, chest, face, and thighs. It was caused by her pencil manufactured of cedar wood that she
was handling at work. In the second case, a carpenter showed a widespread dermatitis of the
buttocks, groins, thighs, legs, and feet owing to a pencil that he used to keep behind his ear.
Positive reactions were obtained with thymoquinone, b-thuyaplicin remained negative. Incense
cedar contains up to 4 percent of thymoquinone (structure, see Thuja plicata).
24.2.2 THUJA
Five Thuja species are known, native to China, Japan, Korea, and North America. Thuja occi-
dentalis L. (Northern white cedar) and T. orientalis L. are cultivated in most countries of the
temperate zone.
Thuja plicata DONN ex D. DON is commonly known as Western red cedar. Western red cedar
is native to the west coast of the United States and British Columbia and exported all over the
world, especially to Europe, Australia, and Japan.
Allergic rhinitis and asthma has been described by Maiden in 1904.108 After the earthquake of
1923 in Tokyo, Western red cedar was exported to Japan for reconstruction of the buildings. Beisugi
asthma, as the allergic symptoms were called in Japan, did not occur only in joiners and carpenters
after sawing and sanding, but also in those individuals living in the houses built from Western red
cedar wood.105,110,156
Occupational asthma owing to the wood was observed as well in other countries, for example,
in South Africa,43,135 Australia,53,115 and especially in its native California and British Colum-
bia.24,168 In the large timber industry of this region, Western red cedar asthma is a common
disease among cedar mill workers. Hundreds of cases have been described because plicatic acid
is abundantly present in Western red cedar.172 Plicatic acid (Figure 24.1) is the responsible
sensitizer.27,29,30,137
Up to 5 percent of the exposed workers developed red cedar asthma.26 About 1 percent developed
an immediate, 44 percent a late, and 48 percent a dual reaction.28 Specific IgE was found in 26
percent with immediate, 21 percent with late, and 26 percent with dual reactions.137
Western red cedar is a timber of good stability useful for construction, venetian blinds, boat-
building, planking, paneling, and framing. Many cases of bronchial asthma observations of occu-
pational allergic contact dermatitis have been reported as well.10,19,136 Suskind succeeded in sensi-
tizing guinea pigs with different extracts of the wood.171 Thymoquinone (see Figure 24.1) must be
considered as the main contact sensitizer, showing a high sensitizing capacity in guinea pig
experiments.65 The safe patch test concentration is 0.1 percent in petrolatum.
24.3 BORAGINACEAE
The Boraginaceae is a family with more than 2300 species in 130 genera growing in tropical and
temperate regions, especially in the Mediterranean area. The chemistry is recorded by Hegnauer.76
24.3.1 CORDIA
The Cordia include Cordia millenii BAKER known as Cordia, Cordia gerascanthus R. BR. known
as Canalete, and Cordia goeldiana HUBER, known as Freijo.
Cordia goeldiana from Brazil, also often called Brazilian walnut, and Cordia gerascanthus
derived from Venezuela together with Cordai millenii and Cordia platythyrsa BAKER from tropical
Africa form a group of valuable timbers with moderate durability. Owing to their light weight,
softness, and low strength, they are used mainly for interior work, furniture, and joinery. Only the
Brazilian species are also suitable for boatbuilding and exterior constructions.
Although used abundantly, only two reports on occupational contact dermatitis are known from
the literature.143,165 However, the author also has seen four cases that remain unpublished. In these
cases, a typical airborne contact dermatitis developed in workers, owing to bad exhaustion condi-
tions, who manufactured balcony breastwork and mouldings.
Moir and Thomson isolated and identified seven quinones from the ethanol extract that was
kindly supplied for patch tests.118,119 The cordiachromes A, B, E, and I (Figure 24.2) gave strong
reactions and, thus, must be regarded as the main sensitizers.
24.4 EBENACEAE
In only 2 genera, 485 species are found occurring in the tropical zone. Most of them are native to
Indonesia and Malaysia. The chemistry is recorded by Thomson.173
24.4.1 DIOSPYROS
Ebony is the name for 475 tropical wood species belonging to the genus Diospyros. Most prized
are those with a deep black heartwood, extreme hardness, and durability. Ebony species are used
for cabinet and inlay work, piano and organ keys, organ stops, violin fingerboards and pegs, parts
of string bows (frogs), and bag pipes.
Diospyros crassifolia HIERN known as African ebony is native to Nigeria, Cameroon, and
Gaboon. African ebony is highly resistant to termites and very hard to work with.
Contact dermatitis has been described by Legge,103 Herxheimer,78 and Lewin.104 Nicholas
reported a case of contact hypersensitivity with reactions on the forearm following the wearing of
an ebony bracelet.130 More recent cases have not been described in the literature.
Diospyros ebenum KOENIG is known as Ceylon ebony. This strong, hard, heavy black wood
is imported in small boles from India, Sri Lanka, Celebes, and the Andaman Islands. Eczematous
reactions of the skin after contact with the sawdust were described by Rasch.144
Diospyros celebica BAKH. is known as Macassar. As the name indicates, the tree comes from
Celebes.
Macassar has been long in use for expensive rulers. Occupational dermatitis may occur but
reports are found rarely in the literature. Buschke and Joseph20 observed hand eczema in a cabi-
netmaker owing to Macassar ebony, while Bleumink and Nater11 obtained positive patch tests to
an ethanol extract of Dalbergia melanoxylon in 4 out of 20 patients suffering from airborne contact
dermatitis owing to tropical woods.
In Macassar, a precursor (Macassar II) of a sensitizing naphtho-ortho-quinone named Macassar
quinone (Figure 24.3) is found as the main constituent. Besides that, more than 17 different naph-
thoquinone derivatives (diospyrin derivatives) have been isolated that possess possibly allergy-
inducing properties.181,182
In 1997, Rackett and Zug observed a 54 year old woodworker business owner who had worked
as a wood turner manufacturing different billiard cues for 26 years.143 The patient suffered from a
pruritic eczematous eruption with scaling of the upper eyelids and forehead. A paddy erythema
and scaling was also seen on the upper abdomen and around the axillae. In the patch test, he reacted
to diluted sawdust (mixed with petrolatum) of the six exotic wood species and, especially, reacted
with a +++-response to Macassar quinone (1 percent petrolatum) from Diospyros celebica. Macassar
quinone is a moderate sensitizer.64
Diospyros melanoxylon ROXB. is known as Coromandel. This ebony species is suspected to
cause allergic contact dermatitis but cases have not been described. Bleumink saw four positive
patch test reactions with Coromandel sawdust in 60 woodworkers handling tropical woods.11 Of
the naphthoquinones, one isolated from Diospyros melanoxylon48 gave a weak sensitizing capacity
in guinea pig experiments.64
24.5 LEGUMINOSAE
The Leguminosae is a cosmopolitan plant family with about 18,000 species in 642 genera. The
family, also called Fabaceae, is divided into different subfamilies with species occurring in the
tropical and temperate zones.
The chemistry is recorded by Dey and Harborne,42 Harborne and Baxter,61 and Thomson.173
24.5.1 LEGUMINOSAE-CAESALPINIOIDEAE
Distemonanthus benthamianus BAILL. is also known as Ayan. Movingui or Ayan is used for
domestic flooring, frames, windows, and cabinetmaking. It is imported from West Africa to England,
where it is mainly used for coffins.
Morgan and Thomson reported a case of severe dermatitis recurring for four years in a carpenter
engaged in making coffins.123 Patch tests were positive with the sawdust and two of the four isolated
flavonoids.96,97 Allergic reactions were observed with oxyayanin A (++++) and oxyayanin B (+++)
(see structures in Figure 24.4).
Woods and Calnan180 described 13 cases of Ayan dermatitis. A case was observed by Orsler in
1969.136
24.5.2 LEGUMINOSAE-MIMOSOIDEAE
24.5.2.1 Acacia
Acacia melanoxylon R. Br. is known as Australian Blackwood and comprises 1200 species in
tropical and subtropical regions.
Australian blackwood (Acacia melanoxylon) is the most important timber for almost every
purpose in Australia. Even fences and musical instruments are manufactured from it. Although
mainly used in its native country, small quantities are occasionally exported to Europe.37
Nott suffered from a rash of his hands and forearms after handling this wood himself.131 Nose-
bleeding and bronchial asthma were recognized by Pulleine in 1925.142 Cleland observed several
cases of weeping dermatitis in joiners and boatbuilders (face, neck, and forearms) connected with
severe itching and conjunctivitis.33,34 Robertson reported one case of asthma and nine cases of
contact dermatitis.148 Though his patch tests remained negative, he suggested that sensitization must
have played a role.
Further observations with positive patch test results have been contributed by Behl in 19669
and Burry in 1969 and 1973.18,19
In a more recent case the wife of a joiner, who was making cabinets in his house, suffered
from allergic contact dermatitis although the working room was in the basement.174 Beside acamelin
and 2,6-dimethoxy-1,4-benzoquinone, the main sensitizer was identified as a hexahydroxyflavan
named melacacidin (Figure 24.5).71 This substance is abundantly found in Acacia species,100 so that
allergic contact dermatitis to related timbers are not uncommon.99
24.5.3 LEGUMINOSAE-PAPILIONOIDEAE
24.5.3.1 Brya
The genus Brya comprises 12 species native to Central America and the West Indies.
Brya ebenus BENTH. (Leg.-Papilionaceae) is known as Cocus. Cocus is a small tree from the
West Indies used for musical instruments, particularly for flutes, recorders, and clarinets. It also
serves for interior turnery, cutlery, and door handles, fancy articles, sawed veneers, and wooden
breakfast platters.
Although of low diameter, it has been imported from Jamaica and Cuba for more than a century
as one of the most valuable woods.
FIGURE 24.6 Cocus I and Cocus II are two sensitizers identified in Bryaebenus (Cocus).
Occupational contact dermatitis has been observed not only in flute-makers sawing and sand-
papering the wood, but also in players of flutes manufactured of this wood. Typically, the allergic
lesions of the latter are swollen lips and mouths.38,113,179
Experimental sensitization of guinea pigs with an ethanol extract was successful.64 A reinves-
tigation of the wood was prompted by the recurrent lesions (swollen lips) developing in a young
girl studying flute. Two hydroxyisoflavans (Figure 24.6) were identified eliciting ++- to +++-
reactions at a 1 percent test concentration.72 A new case was observed recently in a female flute
player of a symphony orchestra (Hausen, B. M., occupational allergic contact dermatitis due to
cocus wood, Akt. Dermatol., 25, 312-314, 1999.)
24.5.3.2 Bowdichia
Four tropical species in South America. Bowdichia nitida BENTH. is known as Sucupira. Sucupira
from Brazil is best suited for structural purposes and mostly used in Europe for flooring. It gains
some interest for turned articles and as a veneer for inlays in high-class furniture. Cases of
occupational contact dermatitis have been described by Freise,50 Dantin-Galego,41 Heyl,79 and
Gonçalo55 in joiners and flooring manufacturers.
Chemical investigation revealed the occurrence of three quinones in the heartwood that were
isolated, purified, and patch-tested in Heyl´s patient. All three quinone fractions produced positive
reactions. The first quinone was identified as 2,6-dimethoxy-1,4-benzoquinone.63 The second
quinone was found to be the first naturally occurring iso-flavone quinone.17 It was named bowdi-
chione (Figure 24.7). The third quinone is still unknown but may be related to the dalbergiones,
as the patient developed cross-reactions to (R)-3,4-dimethoxydalbergion and (S)-4¢-hydroxy-4-
methoxydalbergion. Sensitizing experiments in guinea pigs using the open epicutaneous method
were successful. A reinvestigation of Sucupira wood revealed the occurrence of at least five
quinonoid constituents, all of which gave positive reactions in the sensitized animals (unpublished).
24.5.3.3 Dalbergia
About 100 species growing in the tropical and subtropical regions around the world are known,
some also occur in South Africa. They provide most valuable woods used for high-class furniture,
cabinetwork, inlay work, knife handles, chess pieces, rosaries, and parts of musical instruments.
The chemistry is recorded by Thomson173 and Donnelly.44,45
Dalbergia retusa HEMSL. (D. obtusa LEC.) is known as Cocobolo. Cocobolo derives from
Central America. It is strong, hard, compact, fairly heavy, easy to work, and of extreme durability.
It holds a supreme position in the cutlery trade, especially knife handles, but also serves for brush
backs, chessmen, scientific instruments, bulks of billiard cues, wooden bracelets, wooden jewelry,
and interior turnery. Cocobolo is specially used for musical instruments. Of all recorders manufac-
tured before World War II, 90 percent were made from Cocobolo. Descriptions of occupational
dermatitis occurring in workers manufacturing hairbrushes, knife handles, and recorders have been
published just as often as allergic reactions of the lips and fingertips in those playing the instru-
ments.67,106,117,128,143,160,169 The responsible allergens belong to the class of neo-flavonoids, named
dalbergiones (Figure 24.8). In Cocobolo, obtusaquinone and (R)-4-methoxydalbergion play a major
role while (S)-4¢-hydroxy-4-methoxydalbergion plays a minor role.73 Their sensitizing capacity has
been examined by Schulz et al. in animal experiments.163 Obtusaquinone, chemically near related
to (R)-4-methoxydalbergion and a sensitizer, too, disclosed a similar sensitizing power in the animal
experiments.64
Dalbergia melanoxylon GUILL. & PERR. is known as Grenadill. As a hard and heavy blue-
black colored wood, Grenadill or African blackwood is mainly imported from Mozambique,
Zimbabwe, Togo, and Senegal. Its use comprises knife handles, brush backs, chessmen, truncheons,
flutes, clarinets, oboes, chanters of bagpipes, and some types of recorders.
Cases of allergic contact dermatitis as well as conjunctivitis have been described since 1934
and were seen in clarinetmakers and in knife handle turners.69,113,180 The responsible allergens are
(S)-4-methoxydalbergion, (S)-4¢-hydroxy-4-methoxydalbergion, and (S)-3¢-hydroxy-4,4¢-dimethoxy-
dalbergione (Figure 24.8). Their sensitizing capacity was determined in animal experiments.163
Dalbergia nigra ALL. is known as Brazilian rosewood and Dalbergia latifolia ROXB. is known
as East Indian rosewood. Although of different origins, both rosewoods are used for similar purposes
and contain the same main sensitizers. While Dalbergia nigra is native to Brazil, East Indian
rosewood originally is from India and Malaysia.
The timbers are of attractive appearance when cut from old stems. Imports are low but steady.
Used for high-class furniture and cabinetwork, handles, decorative veneers, wooden jewelry (brace-
lets, necklaces), inlay work, and especially musical instruments, such as flutes, recorders, piano
cases, pegs, bridges of violins, and chin rests. Occupational contact dermatitis has been observed
in cabinetmakers, knife grinders, as well as knife users (e.g., in butchers) and chin rests by
professional violinists.39,49,52,56,70,75,86,111,141,180 Contact allergy owing to a wooden necklace was
reported recently.73
The responsible sensitizers (R)- and (S)-4-methoxydalbergion, (S)-4,4¢-dimethoxydalbergion
and (S)-4¢-hydroxy-4-methoxdalbergion do not only occur in the two species named previously,
but also in Dalbergia stevensonii Standley (Honduras rosewood) that has been found to produce
occupational contact dermatitis as well.13,180 In animal experiments, the dalbergiones showed a
moderate to strong sensitizing activity.163
24.5.3.4 Machaerium
Machaerium scleroxylon TUL. is also known as Pao ferro or “Santos”-Palisander and Caviuna
vermelha. The wood of Pao ferro closely resembles true Brazilian rosewood in appearance and
physical properties and, thus, is frequently used as a substitute or often simply mistaken for real
rosewood. In Europe, Pao ferro is used for furniture, veneers, television sets, knife handles, record-
ers, and multiple other purposes. Outbreaks of occupational contact dermatitis have been reported
not only from its native country Brazil but also from Denmark, Great Britain, Germany, Italy, and
Spain. Altogether more than 100 cases have been described in the literature.7,36,66,116,124,143,149,150
Active sensitization occurred in two nurses who had been used as controls and patch tested with
the pure wood dust. The responsible contact allergen is (R)-3,4-dimethoxydalbergion (Figure 24.9).
This constituent is the strongest sensitizer within the group of dalbergiones.163 Its safe patch test
concentration is 0.01 percent!
In some Pao ferro samples collected from different woodworking factories, up to 4.9 percent
were detected in the heartwood.68 Thus, a patch test with the sawdust itself should strictly be
avoided. Pao ferro is the most hazardous commercial timber in the woodworking industry. (R)-3,4-
dimethoxydalbergion does not occur in the related Dalbergia species.
24.6 MALVACEAE
This family contains about 1800 species in 111 genera growing in tropical and subtropical regions.
24.6.1 THESPESIA
The genus Thespesia comprises 17 tropical species including woods and herbaceous plants. The
chemistry is recorded by Hegnauer.76
Thespesia populnea (L.) SOL. is known as Milowood. Milowood is a small tropical tree
distributed widely throughout the tropics and in many areas of the United States including Cali-
fornia, Florida, and Hawaii. Primarily, it is used for making bowls, bracelets, carved tikis, and
furniture. Among the different mansonones that are known sensitizers from Mansononia altissima,
Milowood contains a new sesquiterpenoidal quinone, named mansonone X (Figure 24.10).114
A 42 year old Hawaiian bowl turner was afflicted for more than 10 years with a purific
eczematous dermatitis, affecting the antecubital fossae, forearms, neck, and lower faces. Patch test
with extracts and isolated fractions were positive. The responsible contact allergen was isolated
and identified as the new mansonone X. In guinea pig experiments, this compound showed a
moderate sensitizing capacity.74
24.7 MELIACEAE
In this family, 565 species in 51 genera are found in warm regions. The chemistry is recorded by
Hegnauer76 and Banerjii.6
Khaya also known as African mahogany comprises seven species in the tropical regions of
Africa including Madagascar. The four species Khaya grandiflora C. DC, Khaya ivorensis A.
CHEV., Khaya anthotheca C. DC, and Khaya senegalensis A. JUSS are timbers of West Africa.
They serve as a substitute for South American mahogany, especially for cabinets, furniture,
boatbuilding, moulding, and other purposes where a good quality wood is required.
Khaya anthotheca C. DC is known as Krala. Outbreaks of contact dermatitis owing to this
species have been described by Morgan and Wilkinson,120,121 Morgan and Orsler,122 Wilkinson,176,177
Morgan et al.,124 Wilkinson et al.,178 Shevljakov,167 Orsler,136 and Hjorth.84 The author, too, observed
two cases in which airborne contact dermatitis had developed to the sawdust of African mahogany.
A patch test with a 10 percent ethanol extract was positive.
The responsible sensitizers are not yet known. One of the allergenic constituents seems to be
anthothecol (Figure 24.11), found in K. anthotheca up to 0.03 percent.122 Besides that, K. anthotheca
and K. ivorensis contain the weak sensitizer 2,6-dimethoxy-1,4-benzoquinone (see Acacia melan-
oxylon). Its sensitizing capacity has been determined experimentally in guinea pigs.64
24.8 MORACEAE
This family comprises about 1100 species in 38 genera. Most of them are trees and shrubs. Only
four species grow in the temperate zone. Some species produce a latex that irritates the skin (e.g.,
Ficus sp.).
Chlorophora excelsa (WELW.) BENTH. (syn. Milicia excelsa (WELW.) C. BERG) is known
as Iroko, Kambala. This West African timber is used frequently as a substitute for Teak because it
possesses many of the desirable features of Tectona grandis. It has been in demand for decades
owing to its strength and durability for construction work, especially windows, door frames, and
shipbuilding.
Occupational contact dermatitis with eruptions of the skin of the forearms, face, neck, and feet
has been described in woodworkers since 1910.8,40,80,92,139,159,161,162 In 1949, King and Grundon94
isolated a hydroxy stilbene, named chlorophorin, that was revealed to be a moderate sensitizer.64,158
Its structure (Figure 24.12), first elucidated by King and Grundon in 1950,95 was corroborated in
1986 by Krohn et al.101
24.9 PROTEACEAE
Found in tropical regions around the world , in the mountains of tropical Africa, South Africa, and
Madagascar, the Proteaceae family comprises about 1600 species in 77 genera. Chemistry is
recorded by Hegnauer,76 Rasmussen,145 Ridley,146 Ritchie,147 and Cirigottis.32
Grevillea robusta A. CUNN. is known as Australian silky oak and is native to the fifth continent,
but it is also grown in Africa, Sri Lanka, India, and the United States. Flooring, furniture, and
FIGURE 24.14 Mansonone A, a strong sensitizer, is one of the sesquiterpenoid mansonone allergens found
in Massonia altissima A. CHEV.
plywood are the main uses, but the tree is also required for telegraph poles and as a shade tree.
Grevillea poisoning is a common term for occupational dermatitis that develops from the sap
contacting the skin during sawing.1,99,112 Bracelets made from Grevillea wood grown in India and
shipped to the United States and other countries were shown to be the source of allergic contact
dermatitis of the forearms, too.85,102 The responsible allergen is grevillol (Figure 24.13), a phenolic
compound with a long side chain that resembles the sensitizing urushiols from poison ivy.
24.10 STERCULIACEAE
About 1500 species in 67 genera are found in tropical areas. The chemistry is recorded by
Hegnauer.76
24.10.1 MANSONIA
Mansonia altissima A. CHEV. is known as Mansonia and Bété. The attractive durable wood of the
Mansonia tree is imported from Nigeria and the Gold Coast and used as a substitute for walnut.
Outbreaks of occupational contact dermatitis have been described in hundreds of cases since 1936,
of which only some were cited.15,60,87,126,152
The responsible allergens belong to the class of sesquiterpenoid mansonones, of which man-
sonone A, a red ortho-quinone is the main (strong) sensitizer (Figure 24.14).161,163 A review of the
chemistry of Mansonia altissima is given in the book by Neuwinger.129 Interestingly, some of these
quinones, for example, mansonone E and F, occur in elm species (Ulmus x hollandica); making
the tree resistant against the Dutch elm disease.
24.10.2 TECTONA
Tectona grandis L. is known as Teak. Of the four species in this genus, teak wood is one of the
most valuable timbers of the world. While native to Burma, India, Thailand, and Malaysia, it also
has been planted in South Africa and the West Indies. Owing to its strong durability, it is used in
furniture, exterior joinery, flooring, fittings, door and window frames, rails, ship building, bridges,
and wharves. Teak is resistant to termites and chemicals and, therefore, can be used outdoors and
for laboratories, too. The chemistry is recorded by Sandermann and Simatupang.154
Occupational contact hypersensitivity has been observed as early as in Ancient Egypt, where
ships were built with teak from India. More recent descriptions date back to the last century and
continue up to the 1970s, when it became one of the most common sensitizers in the wood industry.180
The primary sensitizer is a simple naphthoquinone, named deoxylapachol.153-155 Compared with
other plant allergens, deoxylapachol is one of the strongest sensitizers found in nature.162 Patch
testing with sawdust may produce false-positive reactions owing to its highly irritant properties.
Deoxylapachol may actively sensitize when not patch tested in its safe concentration of 0.01 percent.
Another major constituent of teak is lapachol, equipped with a blocking hydroxy group at the
quinonoid ring that may be tested at 1 percent in petrolatum. Cross reactions between deoxylapachol
and lapachol are obligatory (Figure 24.15).
24.11 REFERENCES
1. Adams, R. M. and Gimenezarnau. J. M., Allergic contact dermatitis caused by the sawdust of Grevillea
robusta A. D. CUNN., Am. J. Cont. Derm., 3, 192, 1991.
2. Alemany-Vall, R., Rhinitis and dermatitis caused by exotic woods, in Occupational Allergy, H. E.
Stenfert Kroese, Leiden, 1958, 273.
3. Anon., Wood dust and the woodworker, Timber Technol., 65, 205, 1957.
4. Azofra, J. and Olaguibel, J. M., Occupational asthma caused by Iroko wood, Allergy, 44, 156, 1989.
5. Bahn, K., Beitrag zur Frage der Allergie bei Holzsägereiarbeitern. Klin. Wsch., 7, 1963, 1928.
6. Banerjii, B. and Nigam, S. K., Wood constituents of Meliaceae. A review, Fitoterapia, 1, 3, 1984.
7. Beck, M. H., Hausen, B. M., and Dave, V. K., Allergic contact dermatitis from Machaerium scleroxylon
TUL. (Pao ferro) in a joinery shop, Clin. Exp. Dermatol., 9, 159, 1984.
8. Beer, W. E., Sensitivity to Iroko wood in a wood machinist, Contact Derm. Newslett., 7, 159, 1970.
9. Behl, D. N. and Captain, R. M., Skin-Irritant and Sensitizing Plants Found in India. Asian Printers
Ltd., New Dehli, 1966.
10. Bleumink, E., Mitchell, J. C., and Nater, J. P., Allergic contact dermatitis from cedar wood (Thuja
plicata), Br. J. Dermatol., 88, 499, 1973.
CONTENTS
25.1 Introduction
25.1.1 Plant Family
25.1.1.1 Geographic location
25.1.2 Species
25.1.2.1 Toxicodendron succedaneum (syn. Rhus succedanea)
25.1.2.1.1 Chemistry
25.1.2.1.2 Clinical Effect
25.1.2.1.3 Treatment
25.1.2.1.4 Cross reactions
25.1.2.2 Toxicodendron vernicifluum (syns. Rhus verniciflua,
Rhus vernicifera)
25.1.2.2.1 Chemistry
25.1.2.2.2 Clinical Effect
25.1.2.3 Toxicodendron striatum (syns. Rhus striata, Rhus juglandifolia)
25.1.2.3.1 Chemistry
25.1.2.3.2 Clinical Effect
25.1.2.4 Other Toxicodendron Species
25.2 References
25.1 INTRODUCTION
25.1.1 PLANT FAMILY
25.1.1.1 Geographic Location
25.1.2 SPECIES
The main species of Toxicodendron to cause dermatological problems are T. radicans (poison ivy)
and T. diversilobum (poison oak) that, with their various subspecies, are found predominantly in
Northern America (see Chapter 9). There are, however, up to 15 other species in the genus
Toxicodendron that may give rise to skin reactions. In the Southern Pacific, the three main allergenic
0–10 35 33 1 34 77 7 4
11–20 21 17 1 17 8 7 7
21–30 3 0 1 2 1 1 1
31–40 10 1 (golf) 8 3 6 5 1
41–50 13 0 6 2 11 6 1
51–60 8 0 9 1 8 6 3
Greater than 61 2 0 4 1 0 1 0
angles to the midrib. These leaves turn orange, red, or scarlet in autumn (Figures 25.1 and 25.2).
Small yellow flowers are followed by pendulous clusters of tawny fruit. The crushed fruits produce
a wax (sumach wax). In Japan, it was formerly cultivated for the fruit that supplied wax for candles,
varnishes, polishes, ointments, and plasters.13 In Indochina it was also used as a lacquer source
although T. vernicifluum is traditionally regarded as the lacquer tree. T. succedaneum has been
extensively planted as a small ornamental garden tree in Australia, New Zealand, and in some South
American countries.11 In Japan, it is also popular for bonsai.14 In the Southern Pacific, the main
contact between humans and T. succedaneum is through gardening.15,16
The leaves, fruit, and bark can all cause dermatitis.5,17 The processed wax has been reported
to cause hand dermatitis in workers handling fabrics waterproofed with the wax.18 The sap is
vesicant.
25.1.2.1.1 Chemistry
The allergen in Toxicodendron are urushiols that contain a mixture of catechols (1,2-dihydroxy-
benzenes) and resorcinols (1,3-dihydroxybenzenes).19-22 The antigenicity of these compounds is
related to the molecular length and unsaturated double-bond content of the side chains. Longer
side-chains increase irritancy and allergenicity. The allergen in T. succedaneum is 3-heptadec(en)yl
catechol. Urushiol is inactivated rapidly in water.
25.1.2.1.2 Clinical Effect
Urushiol is found in the resin canals that course through the leaves, bark, and roots of the plant.
The resin canals do not drain to the surface, so exposure to urushiol usually requires physical
trauma to the plant, but this may be minimal (Table 25.1). In late autumn, however, urushiol is
spontaneously released from the plant. Most cases of contact dermatitis occur after contact with
the plant, but in some sensitive individuals the eruption can develop without apparent direct contact.
As has been reported with T. radicans, we have seen patients in whom the allergen has been
transferred on the fur of a pet, by the wind, or even in smoke of burning plants. After contact with
urushiol, a sensitized individual typically develops an erythematous, pruritic eruption on the face
and arms within two days. When the plant juice contacts the skin indirectly via clothing worn on
an outing or by patting a dog that has run through the bush, the dermatitis tends to have a more
diffuse, patchy appearance.
T. succedaneum is the commonest cause of poison ivy dermatitis in Australia and New
Zealand.15,23,24 In one center in New Zealand, 92 cases of phytodermatitis to T. succedaneum were
seen over a 12-year (1982–1994) period of time.15 Of the patients, 42 were female and 50 were
male with a bimodal age distribution (5–15 years and 35–45 years). Of the younger patients (aged
0–20 years), 90 percent presented with facial dermatitis reflecting facial contact while playing under
the trees (Figure 25.3). In six instances, two or more members of the same family, usually all
children, presented simultaneously with a phytodermatitis. Of the older patients (aged 35+ years),
three fourths presented largely with a dermatitis affecting the upper limbs reflecting contact while
gardening (usually pruning). In a second study examining all cases of phytodermatitis to T. suc-
cedaneum presenting over a 12 month period of time, 75 percent presented during autumn, the
remainder during summer.24
Like allergic contact dermatitis to T. radicans (poison ivy),20,21,25,26 patients allergic to T.
succedaneum present with a vesicular phytodermatitis; namely, linear streaks of erythema and
vesicles. In addition, similar to allergy to T. striatum in South America, facial edema with marked
periorbital swelling is common, particularly in children (Figure 25.3). The severity of the reaction
often results in mistaken diagnosis. Each year a number of the cases, including the patient in
Figure 25.3, are initially treated by nondermatologists with systemic antibiotics for presumed
cellulitis. The linear pattern of vesicles can also be confused with the dermatomal eruption of
shingles (herpes zoster).
It is unclear when T. succedaneum was first introduced in Australia and New Zealand. It is
widespread through both the North and South Island of New Zealand, with at least 20 commercial
nurseries propagating the tree. Most city councils are aware of the allergenic potential of T.
succedaneum. In some Australian States, T. succedaneum has been voluntarily banned from sale
after seven workers in one nursery were affected through handling of the plant.10,27 Unfortunately,
it is still available from garden centers in New Zealand, although a warning is usually given to
potential purchasers. It has been estimated that, in New Zealand, T. succedaneum may be found in
up to 1 in 200 private gardens.
Less common species of Toxicodendron include Toxicodendron borneense (syn. Rhus borneensis)
that is native only to northern Borneo and Toxicodendron nodosum (syns. Rhus nodosa and Rhus
perakensis) that is found in the Malay archipelago.1 Both can probably induce contact dermatitis.
In the Southern Pacific, specimen trees are confined to botanical collections.
25.4 REFERENCES
1. Gillis, W. T., The systematics and ecology of poison-ivy and the poison-oaks (Toxicodendron, Anac-
ardiaceae), Rhodora, 73, 72, 161, 370, 465, 1971.
2. Beaman, J. H., Allergic Asian Anacardiaceace, Clin. Dermatol., 4, 191, 1986.
3. Cleland, J. B., Plants, including fungi, poisonous or otherwise injurious to man in Australia, Austr.
Med. Gaz., 35, 569, 1914.
4. Standley, P. C., Poisonous trees of Central America, Trop. Woods, 9, 3, 1927.
5. Burry, J. N., The value of patch testing: a review of 363 cases of allergic contact dermatitis, Med. J.
Austr., 1, 1226, 1969.
6. Nurse, D. S., Poison ivy in Melbourne, Med. J. Austr., 1, 528, 1966.
7. Turner, T., Poison ivy and poor-man’s liquid amber, Med. J. Austr., 2, 166, 1972.
8. Apted, J. H., Poison ivy dermatitis in Victoria, Austr. J. Dermatol., 19, 35, 1978.
9. Apted, J. H., American poison ivy (Rhus radicans) in Australia, Int. J. Dermatol., 19, 81, 1980.
10. Aplin, T. E., Plants that cause dermatitis, Austr. J. Dermatol., 22, 33, 1981.
11. Hurtado, I., Poisonous Anacardiaceae of South America, Clin. Dermatol., 4, 183, 1986.
12. Nakamura, T., Contact dermatitis to Rhus succedanea, Contact Derm., 12, 279, 1985.
13. Usher, G., A Dictionary of Plants Used by Man, Constable, London, 1974.
14. Murata, K., Practical Bonsai for Beginners, (transl. by Tsuzawa, M. and Mann, D. C.), Japan
Publications Trading Co., Tokyo, 1964.
15. Rademaker, M. and Duffill, M. B., Toxicodendron succedaneum (Rhus tree), New Zealand’s poison
ivy, Contact Derm., 33, 357, 1995.
16. Cook, D. K. and Freeman, S., Allergic contact dermatitis to plants: an analysis of 68 patients tested
at the Skin and Cancer Foundation, Austr. J. Dermatol., 38, 129, 1997.
17. Guimaraes, O. P., Bento, D., Pickel, J., et al., The toxico-allergic principle of the Anacardiaceae. The
problem of Rhus succedanea in the city of Sao Paulo, Rev. Bras. Med., 17, 43, 1960.
18. Schwartz, L., Tulipan, L., and Birmingham, D. J., Occupational Diseases of the Skin, 3rd ed., Lea
and Febiger, Philadelphia, 1957, 637.
19. Baer, H., Chemistry and immunochemistry of poisonous Anarcardiaceae, Clin. Dermatol., 4, 152,
1986.
20. Lovell, C. R., Plants and the Skin, Blackwell Scientific Publications, Oxford, 1993.
21. Mitchell, J. C. and Rook, A., Botanical Dermatology: Plants and Plant Products Injurious to the
Skin, Greengrass, Vancouver, BC, 1979.
22. Connor, H. E., The Poisonous Plants of New Zealand, 2nd ed., Government Printer, Wellington, 1977.
CONTENTS
26.1 Introduction
26.2 Origin of Spices and Herbs
26.3 Constituents of Spices and Herbs
26.4 Irritant and Allergic Reactions to Spices and Herbs
26.4.1 Immediate Nonallergic Skin Reactions
26.4.2 IgE-Mediated Allergy
26.4.2.1 Skin Testing with Spices and Herbs
26.4.2.2 RASTs with Spices
26.4.2.3 Immediate Skin Challenge Reactions
26.4.2.4 Immediate Skin Reactions to Ingested Spices .
26.4.2.5 Allergens for Skin Prick Testing and RASTs
26.5 Delayed Type Allergy
26.5.1 Proteins
26.5.2 Chemicals
26.5.3 Systemic Contact Dermatitis
26.5.4 Patch Testing
26.6 References
26.1 INTRODUCTION
Aromatic seeds, fruits, roots, buds, flowers, and barks of certain plants used to flavor foods and
beverages, mostly native to the tropics, are called spices or genuine spices. Herbs are another group
of aromatic plants used in foods and beverages to enhance or replace the flavor of spices. Herbs
can be divided into nine categories, namely culinary, salad, scented, strewing, and medicinal herbs,
and into berry vegetables, tea herbs, and dye plants.1 The borderlines between the different herb
categories and between spices and culinary herbs are poorly established. In addition to spices and
herbs, natural or synthetic essential oils are often added to our daily food both at home and in the
food-processing industry. Spices and herbs cause both irritant and allergic skin reactions that may
be immediate or delayed, local or systemic. Most of the reactions are mild and harmless, but
widespread dermatitis or anaphylactic reactions may occasionally develop. Owing to the high
number of aromatic plants, only plants belonging either to genuine spices or to common culinary
herbs are discussed in this chapter.
* Unripe berry.
** Ripe berry.
*** Genus of up to 10 species.
oriental mustards and named, respectively, as Bra j 1 and Sin a 1.6-8 Several other proteins with
molecular weights ranging from 12 to 90 kDa have been detected in anise, coriander, ginger, cumin,
and curry,9,10 but their amino acid sequences have not been identified yet. In a case of a systemic
reaction after ingestion of oregano and thyme, obvious cross allergy was found between thyme,
oregano, hyssop, peppermint, and sage but not for lavender and basil.10
In IgE-mediated cross allergy, plant profilins have been found to be responsible for most
reactions between pollens, vegetables, and spices.12-14 In birch pollen, Bet v 1 and Bet v 2 are the
most common, but not the only cross-reacting proteins.15 Untoward reactions to genuine spices by
patients with several plant cross allergies are usually mild.13 Severe reactions have occasionally
been reported from occupational exposure.13, 16-18
1. Allergens
Carnosol Salvia carnosa, S. officinalis, S. canariensis,
S. calycina, S. triloba, Rosemary
Carvone Caraway, dill, spearmint
Cinnamic aldehyde Cinnamon, cassia
Dipentene Cardamom
Eugenol Jamaica pepper, clove, basil, lemon balm
Sesquiterpene lactones Laurel, Asteraceae family
2. Irritants
Capsaicin Capsicum annuum
Cinnamic aldehyde* Cassia, cinnamon
Isothiocyanates** Mustards
3. Photosensitizers
Bergapten Angelica, rue
reaction is merely edema restricted to the contact area of the spice or spice extract. Patients with
nonimmunologic immediate skin test reactions to spices develop no symptoms or signs from
ingested spices. However, irritant hand dermatitis may result from repeated exposures to spices in
food handlers.19
Jamaica pepper, vanillin, clove, white pepper, ginger, cardamom, cinnamon, and paprika, and one
spice mixture, curry, scratch-tested in 779 to 1038 atopics produced positive reactions in 0.4 to
17.4 percent.12 The twelve spices of curry (nutmeg, black pepper, turmeric, clove, ginger, cinnamon,
white pepper, cardamom, mustard, cayenne, caraway, and coriander) were scratch tested separately
in 71 patients reacting to curry. Coriander was positive in 42 (59 percent), caraway in 39 (55
percent), cayenne in 32 (45 percent), and mustard in 23 (32 percent) of them, while positive
reactions to the other components of curry were seen in less than 4 percent of the patients tested.
Highly significant positive correlations were seen between reactions to curry and birch pollen,
and between curry and fruits and vegetables, especially carrot.12 In the same study, over 300
nonatopics were also scratch tested and 1.3 percent of them showed a positive result to 1 of the
9 spices. Vanillin, white pepper, ginger, cinnamon, and curry caused a positive reaction in one
patient each.
26.5.2 CHEMICALS
Spices and their essential oils were already known to produce contact dermatitis more than 100
years ago, vanilla and cinnamon being the causative spices (see Reference 2). Vanilla allergy was
seen in vanilla factories and bakeries, and cinnamon allergy in bakeries. In his extensive study on
balsams, Hjorth40 laid the basis for our present knowledge of the frequency and significance of
contact allergy to balsams and spices containing the same or related essential oils and other odorous
substances. Balsam of Peru contains 60 to 70 percent of benzyl benzoate, benzyl cinnamate,
cinnamic acid, benzoic acid, vanillin, farnesol and nerolidol, and 60 to 70 percent of unknown
resins of an unknown composition.40,41 The list of fragrance materials capable of causing contact
allergy comprises roughly 100 chemicals.42 Many of them are present in spices and herbs.
Among 118 dermatological patients with contact allergy to balsam of Peru, positive patch test
reactions to clove were seen in 46 percent, to Jamaica pepper in 21 percent, and to cinnamon in
15 percent, whereas ginger, curry, cardamom, white pepper, vanillin, and paprika were positive in
less than 10 percent of the cases. Only 3 positive reactions were seen in 220 other dermatitis patients
not allergic to balsam of Peru.43 Occupational exposure to spices may cause contact allergy to them
without concomitant balsam of Peru allergy.17
Essential oils of 12 spices were patch-tested on 539 dermatitis patients with a positive result
in 27 percent.44 A majority of the patients with positive responses reacted to an average of 2 of
the 12 oils. Reactions to oils of lavender and caraway were encountered especially in those who
26.6 REFERENCES
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1995.
4. Bremness, L., The Complete Books of Herbs, Borling Kindersley Ltd., London, 1988.
5. Reynolds, J. E. F., Ed., Martindale. The Extra Pharmacopoeia, 31st ed., Royal Pharmaceutical Society,
London, 1996.
6. Menéndez-Arias, L., Moneo, I., Domínguez, J., and Rodríguez, R., Primary structure of the major
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characterization of a major allergen from oriental mustard seeds, Bra j 1, Int. Arch. Allerg. Appl.
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with celery, apiaceous spices and birch pollen, Ann. Allerg., 70, 495, 1993.
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report, Allergy, 34, 327, 1979.
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spices, Allergy, 51, 117, 1996.
19. Niinimäki, A., Scratch-chamber tests in food handler dermatitis, Contact Derm., 16, 11, 1987.
20. Wütrich, B. and Dietschi, R., Das “Sellerie-Karotten-Beifuss-Gewürz-Syndrom”. Hauttest- und RAST-
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