Marles & Farnsworth 1995 Antidiabetic Plants

Phytomedicine Vol. 2 (2), pp.
137-189, 1995
@
Review alilcie
1995 by Gustav Fischer Verlag, Stuttgart Jena . New York
Antidiabetic plants and their active constituents1

R. J. MARLEsa and N. R. FARNSWORTHb
Department of Botany, Brandon University, Brandon, MB R7A 6A9, CANADA
b Program for Collaborative Research in the Pharmaceutical Sciences, College of Pharmacy, University of
Illinois at Chicago, Chicago, Illinois 60612, U.S.A.
Summary
Diabetes mellitus is a debilitating and often life-threatening disease with increasing incidence in
rural populations throughout the world. A scientific investigation of traditional herbal remedies
for diabetes may provide valuable leads for the development of alternative drugs and therapeutic
strategies. Alternatives are clearly needed because of the inability of current therapies to control
all of the pathological aspects of diabetes, and the high cost and poor availability of current therapies for many rural populations, particularly in developing countries. This review provides information on more than 1200 species of plants reported to have been used to treat diabetes
and/or investigated for antidiabetic activity, with a detailed review of representative plants and
some of great diversity of plant constituents with hypoglycemic activity, their mechanisms
of action, methods for the bioassay of hypoglycemic agents, potential toxicity problems, and
promising directions for future research on antidiabetic plants. The objective of this work is to
provide a starting point for programs leading to the development of indigenous botanical resources as inexpensive sources for standardized crude or purified antidiabetic drugs, and for the
discovery of lead compounds for novel hypoglycemic drug development.
Key words: antidiabetic plants, botany, chemistry, mechanism of action, bioassays for hypoglycemic agents.
Introduction
At least 30 million people throughout the world suffer

from diabetes mellitus. Life expectancy may be halved by
this disease, especially in developing countries where its
prevalence is increasing and adequate treatment is often unavailable. Even in developed countries such as the USA,
where sophisticated therapy is widely available, more
deaths are attributed to diabetes than to lung cancer, breast
cancer, or motor vehicle accidents (World Health Organization 1985).
Diabetes not only kills, but is a major cause of adult
blindness, kidney failure, gangrene, neuropathy. heart attacks, and strokes. In the USA, where there are an estimated 14 million diabetics (Bransome 1992), the economic im1 Reprinted. with revisions and additions, from Economic and
Medicinal Plant Research Volume 6. Academic Press ltd., 1994,
with permission.
pact of the disease is enotmous. In 1987 an estimated 5.7

million hospital days were attributed to the treatment of diabetic complications, with an additional 2 million labor
days lost to out-patient physician visits and work loss. Direct medical costs due to diabetes are estimated to have
been $9.6 billion, and indirect costs for short-term morbidity, long-term disability, and mortality (more than 80,000
deaths) are estimated to have been $10.6 billion (Center for
Economic Studies in Medicine 1988).
There has been a striking emergence of non-insulin-dependent diabetes mellitus as a major health problem in
populations undergoing modernization of life-style, both in
developing nations and in rural areas of developed countries (Bennett 1983, Bransome 1992, World Health Organization 1985, Gohdes 1986, Schraer et al. 1988). The enormous costs of modem treatment indicate that alternate
strategies for the prevention and treatment of diabetes must
be developed. Since almost 90 % of the people in rural are-
138
R. J. Maries and N. R. Farnsworth
as of developing countries still rely on traditional medicines

for their primary health care, and scientific investigations
of traditional medicines have led to the discovery of at least
88 drugs now in professional use worldwide (Soejarto and
Farnsworth 1989), a synthesis of local traditional and modern knowledge and techniques for the management of diabetes should be feasible. A rationally designed interdisciplinary research program could lead to the development of indigenous, renewable, medicinal plant resources as practical
and cost-efficient alternatives. The purpose of this review is
to provide the information needed for the design of such a
project.
Background: Diabetes Classification

and Modern Therapy
Diabetes mellitus comprises a group of etiologically and

clinically heterogeneous disorders with a common set of
symptoms: excessive thirst and hunger, muscular weakness
and weight loss, excessive urination, and elevation of the
blood glucose level which, when it exceeds the renal threshold, results in the excretion of glucose in the urine. These
symptoms were described by the ancient Egyptians in the
Ebers Papyrus about 3500 years ago (Hengesh and Holcomb 1981), and by the Greek physicians Aretaeus the
Cappadocian (A.D. 30-90) and Galen (A.D. 130-200)
(Farnsworth and Segelman 1971).
There are three main types of diabetes mellitus recognized by the World Health Organization (1985). Insulin-dependent diabetes mellitus (IDDM) requires daily injections
of insulin to prevent a catabolic cascade culminating in diabetic ketoacidosis, coma, and death. It is characterized by
the virtual absence of p-cells from the islets of Langerhans
in the pancreas, and a level of insulin secretion insufficient
to restrain excessive secretion of glucagon or to counter its
enhancement of hepatic glucose and ketone production.
The loss of J3-cells may be due to exogenous chemicals from
the environment or diet, viral infection, or immunological
factors such as an autoimmune disorder in genetically vulnerable individuals (Unger and Foster 1985).
Non-insulin-dependent diabetes mellitus (NIDDM, also
known as Type II or maturity-onset) occurs predominantly
in older people, e.g. 16.8 % of persons over 65 years of age
in the United States have NIDDM, and it is often associated with obesity (I1arde and Tuck, 1994). NIDDM represents a variety of diabetic states in which the J3-cells are usually low in number relative to a-cells and insulin secretion
is usually sufficient to oppose the ketogenic actions of glucagon but not to prevent hyperglycemia. The basal rate of
hepatic glucose production is elevated in subjects with
NIDDM and this is positively correlated with the degree of
fasting hyperglycemia. This increased rate of glucose release by the liver results from impaired hepatic sensitivity to
insulin, reduced insulin secretion through impaired p-cell
responsiveness to glucose, and increased glucagon secretion

through a reduced ability of glucose to suppress glucagon.
The efficiency of glucose uptake by the peripheral tissues is
also impaired due to a combination of decreased insulin secretion and defective cellular insulin action (insulin resistance) (Porte and Kahn 1991). Receptor mediated insulin
resistance may be a consequence of various factors including increased serine/threonine phosphorylation of the receptor with decreased tyrosine phosphorylation, receptor
desensitization, auto-antibodies to the receptor and inherited structural defects in the insulin receptor. Defects in insulin action could also arise at post-receptor events particularly glucose transport. Other circulating hormones such as
islet amyloid polypeptide (amylin) may also cause insulin
resistance (Pillay and Makgoba 1991).
Malnutrition-related diabetes mellitus (MRDM) refers to
the condition of young diabetics in tropical developing
countries with a history of nutritional deficiency and a set
of symptoms which fail to meet the criteria used to classify
IDDM and NIDDM. The subclass, "fibrocalculous pancreatic diabetes" (FCPD), is believed to be associated with
the consumption of foods containing cyanogenic glycosides, such as cassava (Manihot esculenta Crantz, Euphorbiaceae). The other main subclass, "protein-deficient pancreatic diabetes" (PDPD), is believed to be associated with
early childhood malnutrition conditions such as kwashiorkor in which p-cell damage occurs (World Health Organization 1985, McMillan and Geevarghese 1979). Both
FCPD and PDPD may be forms of NIDDM complicated by
dietary factors, and thus not necessarily associated with living in a tropical developing country (Alberti 1988).
Although this classification of diabetes mellitus is actually too simplistic to properly explain the etiology of the disease in most individuals, since a wide range of factors may
determine the expression of diabetic symptoms (Rossini et
al. 1988), it is still a clinically useful scheme for determining the appropriate therapeutic method.
Modern therapy of IDDM began with the discovery of
the involvement of the pancreas in diabetes by von Mering
and Minkowski in 1889, and the demonstration by Banting
and Best in 1921 that an extract of beef pancreata could
successfully lower blood glucose levels in pancreatectomized dogs. Their use of a pancreatic extract in a human diabetic in 1922 marked the first use of the pancreatic antidiabetic principle, insulin, in the treatment of diabetes mellitus. Several different preparations of bovine, porcine, and
human insulin (1, in Fig. 1) are now available, including
lente or long-acting forms, and a regimen of daily injections
represents the current standard of therapy for IDDM (Hengesh and Holcomb 1981).
Insulin acts by binding to a cell membrane tetrameric
protein receptor which consists of two extracellular a- and
two transmembrane p-subunits. Binding of insulin to the asubunit causes autophosphorylation of J3-subunit intracellular tyrosine residues. The activated insulin receptor then
Antidiabetic plants and their active constituents

gl y~ i
139
le-cys - ser-leu- tyr"gln-Leu-glu-asn-tyr-cys-asn

10
le~v.lgluglncys-cys-thr-ser- j
s~
ph.-val- n-gln-hi .-Iou-cys-gl y-ser-hi s-Ieu-val-glu-ala-leu-tyr-Ieu- val-cys-gl y-g lu-.rg-gl y-phe-ph.- tyr-thr
.---J
pro-Iy.-thr
30
8
9 10
.ll-ser-val
thr-ser- i Ie
Boyine insul in:

Porcine insuL in:
30
ala
ala
N~S02NHC(=O)NH-o
E
~
CI
OCH 3
'.0
HN-<N~
NHCNH 2
II
NH
Fig. 1. Insulin and some synthetic oral hypoglycemic drugs.
couples to cytosolic receptor substrates which can affect

different signalling cascades eliciting the pleiotropic hormone response on cell metabolism and growth. Most of the
proteins involved in the signal transduction pathway of insulin are not known yet, but each of them may playa role
in the various forms of insulin resistance (Muller-Wieland
et al. 1993).
Insulin is a polypeptide drug which would be subject to
digestion in the stomach and small intestine if taken orally.
Preparations for nasal and rectal administration have been
developed. Low biological efficacy restricts their use but
absorption-promoting mechanisms are being developed
and easier administration and acceptance by patients is encouraging the development of new intranasal insulin preparations (Gizurarson and Bechgaard 1991). Insulin can be
combined with protease inhibitors for administration in the
ileum and the ascending colon (Damge et al. 1988). How-
ever, the oral route is the most practical for patients. This
has been achieved by encapsulation of insulin in liposomes,
impervious polymer films, or in polyalkylcyanoacrylate
nanocapsules which can pass through the intestinal epithelium (Damge et al. 1988, Saffran et al. 1986).
Unfortunately, although administration of insulin orally
or by injection reverses the main symptoms of diabetes,
with a return to a near-normal life expectancy, it does not
prevent all of the metabolic defects of diabetes, nor does it
prevent all the diabetic complications from developing. It is
believed that the problem lies in the fluctuation of blood
glucose levels caused by injection of insulin, and several
methods are being developed to achieve a more constant
state of normoglycemia, including portable insulin pumps
with blood glucose monitors for feedback regulation (Pfeiffer 1987), allotransplantation of pancreatic islet endocrine
aggregates (Kakizaki et al. 1987), and fetal or dispersed
140
R. J. Marles and N. R. Farnsworth
adult pancreas transplantation (Hellerstrom et al. 1988).

Treatment with an insulin pump or multiple daily injections
still differs from the natural situation because exogenous
insulin is entering the peripheral circulation first rather
than the liver and these methods do not perfectly imitate
the pulsatile character of insulin secretion nor the rapid
post-prandial rise of insulin levels and subsequent rapid
drop. Microencapsulation of pancreatic islets has been attempted in spontaneously diabetic models, but variable results were obtained due to fibrosis of the capsules. This can
be minimized by purification of the capsule material (sodium alginate-poly-L-lysine) and decreasing the size of the
microcapsules (Clayton et al. 1993). Hybrid artificial pancreas consist of insulin-secreting pancreatic tissue surrounded by a membrane that protects the tissue from rejection by the immune system following implantation. Unresolved problems with this mode of therapy include biocompatibility, oxygen supply limitations, and prevention of immune rejection (Colton and Avgoustiniatos 1991).
Due to the immunological nature of some cases of
100M, treatment with immune suppressants has been attempted. Cyclosporin is only temporarily effective in
100M and its use is not recommended (Faulds et al. 1993).
Therapy of NIDDM involves modifications of lifestyle
and diet, an exercise regimen, and use of oral hypoglycemic
agents (Fig. 1). Dietary modifications include limiting total
caloric intake, increasing the percentage of calories from
complex carbohydrates and reducing the intake of fats and
cholesterol (Ilarde and Tuck, 1994). To be effective, therapeutic interventions for NIDDM must reduce heptic glucose production either by improving islet dysfunction and
raising plasma insulin levels, or improving the effectiveness
of insulin on the liver (Porte and Kahn 1991). The use of
oral hypoglycemic drugs may be effective in controlling
blood glucose levels, but may not prevent all the complications of diabetes (Unger and Foster 1985).
Observations in the 1940's that certain sulfonamide antibiotics, used to treat typhoid fever and pneumonia, caused
the side-effect of hypoglycemia led to the development of
the sulfonylurea hypoglycemic agents. Tolbutamide (2) was
the first, approved for use in the United States in 1957. Although the "first generation" drug chlorpropamide (3)
causes side effects more often, the incidence of severe hypoglycemia, the major lethal side effect, is at least as high with
the "second generation" glyburide (4). To lower the incidence of this problem gliclazide (5) was developed. Its
mechanisms of action involve stimulation of insulin secretion through the j3-cell sulfonylurea receptor, involving closure of K+ ATP channels, and possibly through a direct effect on intracellular calcium transport. and also reduction
of hepaeic glucose production and improvement in glucose
clearance. This is accomplished without changes in insulin
receptors, suggesting a pose-receptor effect on insulin action perhaps by stimulation of hepaeic fructose-2,6-bisphosphatase and muscle glycogen synthetase. Additional
effects of gliclazide beneficial for the prevention of diabetic

microangiopathic complications include reduction of platelet adhesion, aggregation and hyperactivity, and increased
fibrinolysis (Campbell et al. 1991, Alberti et al. 1994). Possible detrimental side effects of sulfonylureas include hyponatremia, dermatological reactions, hepatitis, and hematologic effects (Ferner 1988).
None of the currently available sulfonylureas completely
normalize insulin secretion and action (Beck-Nielsen et al.
1988). Failure to respond to sulfonylurea drugs may be primary (25 % to 30 % of initially treated patients) or secondary, occurring in 5 % to 10 % of patients per year (Ilar-de
and Tuck 1994), e.g. when NIDDM is a transitional state
preceding 100M. Combination therapy with insulin and a
sulfonylurea agent only slightly improved glycemic control
in NIDDM patients - less exogenous insulin was needed
but fasting serum insulin levels showed no difference
berween treatment groups. This therapy did not produce
near-normal blood glucose levels and so it is not recommended for poorly controlled NIDDM patients receiving
insulin (Peters and Davidson 1991).
Another class of drugs, the biguanides, was also shown to
be effective, and phenformin (6) was approved in 1959, but
due to its association with fatal lactic acidosis it was recalled in 1977. Metformin (7) is a less toxic biguanide
which can be a useful adjunct in NIDDM therapy, since it
improves peripheral sensitivity to insulin through a stimulated tissue glucose uptake by a transporter-linked system
(Sirtori and Pasik 1994).
Other therapeutic options for NIDDM include the use of
insulin-sparing antihyperglycemic agents such as a-glucosidase inhibitors, thiazolidinediones, chloroquine or hydroxychloroquine, or fibric acid derivatives such as clofibrate. Other experimental agents include fatty acid oxidation inhibitors and dichloroacetate. To prevent the complications arising from the spectrum of clinical and metabolic
abnormalities which arise from insulin resistance other specific agents may be used including antihypertensives, lipid
lowering agents and sorbitol inhibitors (Ilarde and Tuck
1994). Insulin-like growth factor-1 (IGF-1) produced by recombinant DNA technology is being used in NIDDM patients to stimulate glucose uptake, improve glucose tolerance. decrease hyperinsulinemia and decrease hypertriglyceridemia. Since it improves metabolic control in patients
with extreme insulin resistance it is a useful therapeutic adjunct (Kolaczynski and Caro 1994).
From this brief overview of diabetes classification and
modern therapy, it can be seen that current methods of
treatment for all types of diabetes mellitus fail to achieve
the ideals of normoglycemia and the prevention of diabetic
complications. Promising fields of research such as pancreatic transplants offer little hope to the majority of the
world's diabetics, for whom such procedures will be too expensive and difficult to obtain. Most developing countries
cannot even afford adequate conventional therapy at the
Antidiabetic plants and their active cQnstituents

1987 average U.S. price Qf $14.28 per oral hYPQglycemic
prescriptiQn, Qr $14.23 per insulin prescriptiQn (Center fQr
EcQnQmic Studies in Medicine 1988).
Further prQblems with cQnventiQnal therapy in develQPing cQuntries include insulin supply, storage, and injectiQn,
dietary cQntrQl and cQmplicatiQns frQm malnutritiQn, a
lack Qf trained health care wQrkers, and a lack Qf educatiQn
fQr the patients (Gill 1988). In such situatiQns the incidence
Qf diabetes-related mQrtality is far greater than in wellserved urban areas. There is, therefQre, a clear need fQr alternate SQurces Qf bQth Qral and parenteral antidiabetic
drugs and alternate strategies fQr diabetes therapy.
Plants and the Treatment of Diabetes Mellitus
141
Table 1. Plant Families Most Often Cited for Antidiabetic Activity.

Family
Species cited
Total species'
Fabaceae
Asteraceae
Lamiaceae
Liliaceae
Poaceae
Euphorbiaceae
127
98
36
35
30
30
18,000
21,300
3,500
6,460
10,000
7,000
"According to Thorne (1981).
Qften useful in the discQvery O'f new plants with biO'IO'gically active cQnstituents, it will be necessary to learn mO're
abQut particular grO'UPS Qf hYPQglycemic natural prO'ducts
and their mechanisms Qf actiO'n befO're this methQd Qf drug
discO'very can be successfully emplQyed.
Half O'f the species fQund in Qur literature review have
been used in traditiO'nal medicine to' treat symptQms O'f diabetes. Half O'f these traditiO'nal remedies have had sO'me experimental testing fO'r hypoglycemic activity, e.g., in normal, glucO'se-loaded, allO'xan- or streptQzQtO'cin-induced diabetic, or naturally diabetic subjects. DistinctiQns Qf the experimental mQdel used are clearly impO'rtant fO'r gaining an
understanding Qf the mechanism Qf actiQn of these bQtanical drugs. Further details Qf the biQassay methQds cO'mmO'nly used and their significance fO'r the discQvery Qf new antidiabetic agents will be prQvided belQw.
A summary of the results of screens fQr blQQd glucQse
lO'wering activity, presented in Table 2, shQWS that 81 % Qf
thQse traditiO'nal antidiabetic plants tested gave PQsitive results. Even fO'r thQse plants fO'r which nO' traditiQnal use was
mentiQned, 47 % Qf those species screened were active.
This rate Qf PO'sitive results is higher than Qne WQuid expect
by random chance - perhaps 10 % WO'uid be reasQnable,
based Qn the number of active species Qbtained by the U.S.
NatiO'nal Cancer Institute's random screening O'f mO're than
35,000 species fQr antitumor activity (Spjut and Perdue
1976). The high percentage Qf active plants prO'bably reflects, at least in part, the great variety Qf PQssible active
cO'nstituents and mechanisms O'f actiQn, the PQssibility that
nO't all negative results were repQrted, and fO'r the nO'n-traditional plants, Qther cO'nsiderations made in selecting them
fO'r study (e.g. chemQtaxQnO'mic). Nevertheless, it is clear
from the above results that the study of traditiQnal remedies fO'r diabetes mellitus yields an excellent return in potential new sources of antidiabetic drugs.
If the same O'r a closely related plant is used traditiO'nally
for the same purpQse in mQre than Qne cQuntry, it suggests
TraditiQnal medicines fQr the treatment Qf diabetes mellitus are probably based mainly Qn treatment Qf its QbviQUS
symptQms Qf prQnQunced thirst and PQlyuria. Even glycQsuria was recQgnized as a symptQm Qf diabetes in ancient
Ayurvedic medical texts such as the Sushruta Samhita and
Charaka Samhita (Nagaraj an et al. 1982). The Greek physician Aretaeus recQmmended treatment Qf diabetes by
treatment Qf the profQund thirst. FQr this he recQmmended
starting with a purgative to' strengthen the stQmach, fQllQwed by cQnsuming water bQiled with autumn fruit (a
gQQd SQurce Qf sQluble fibre and cQmplex carbQhydrates
like pectin), milk, gruels Qf a variety Qf whQle grains (an excellent SQurce Qf sQluble and insQluble fibre and glycans),
and astringent wines (alcQhQl is hYPQglycemic accQrding to'
Hengesh and HQlcQmb 1981, LQmeQ et al. 1988). He alsO'
recQmmended a crude drug Qf animal Qrigin: venQm Qf the
"dipsas" viper, which in bite victims causes a severe thirst.
Aretaeus suggested it CQuid be used as a mithridate, i.e., a
PQisQn which is deliberately administered in small, gradually increasing dQses in Qrder to' develQP an immunity to' the
effect Qf the PQisQn (Adams 1856). In fact, the venQm Qf the
Middle Eastern viper PiscivQrus PiscivQrus (Crotalidae)
was fQund to' be hYPQglycemic when administered i.v. at a
dQse Qf lOJ.1g!kg in nQrmal rats and rabbits, but was inactive against allQxan-induced hyperglycemia in rats (Taha
1982).
MQre than 1200 species Qf Qrganisms have been used ethnQpharmacQIQgically Qr experimentally to treat symptQms
Qf diabetes mellitus (see the Appendix). They represent
mQre than 725 genera in 183 families, extending phylQgenetically all the way frQm marine algae and fungi to advanced plants such as the cQmpQsites. The mQst frequently
cited families are shQwn in Table 1. These are very large
and widely distributed families, SO' the large number Qf spe- Table 2. Activity of Traditional Antidiabetics vs. Other Plants.
cies repQrted to' have been used traditiQnally Qr experimenOthers
Traditionals
tally fQr the treatment Qf diabetes may be cQincidental. The
295"
541
phylQgenetic distance between even this select group Qf Total no. tested
254 (47%)
238 (81 %)
families is a strong indicatiQn Qf the varied nature Qf the ac- Total active
tive cQnstituents. Thus, while chemQtaxQnQmic studies are
Out of a total of 582 known traditionally used plants
d
142
R.]. Marles and N. R. Farnsworth
Table 3. Most Widely Used Traditional Antidiabetic Plants.

Scientific name
CUCURBITACEAE
Momordica charantia
APOCYNACEAE
Catharanthus roseus
Countries where used traditionally

Saudi Arabia, West Africa, Pakistan, India, Sri Lanka, Thailand, Fiji, Bimini, Panama, Puerto Rico,
Belize, Jamaica, Trinidad, Virgin Islands, England
Australia, England, Thailand, Natal, Mozambique, India, Philippines, Vietnam, Dominican Republic,
Jamaica
ANACARDIACEAE
Anacardium occidentale
Ecuador, Colombia, Mexico, Venezuela, Jamaica, Madagascar, India, Thailand, England
MYRTACEAE
Syzygium cumini
Eucalyptus globulus
India, Pakistan, Thailand, West Indies, USA, Portugal

West Indies, Mexico, Guatemala, China
FABACEAE
Lupinus albus
Trigonelfa foenum-graecum
Canary Islands, India, Israel, Portugal, Morocco

Israel, Egypt, France, India
LILIACEAE
Aloe vera
Allium cepa
Allium sativum
Haiti, India, Tunisia, Kuwait, Saudi Arabia

India, Saudi Arabia, North Africa, Peru
India, Saudi Arabia, Mexico, Venezuela
BIGNONIACEAE
Tecoma stans
India, Mexico, Guatemala, Virgin Islands, Cuba
URTICACEAE
Urtica dioica
England, USA, Guatemala, Nepal, India
ASTERACEAE
Taraxacum officjnale
Europe, Costa Rica, Mexico, USA
CYPERACEAE
Kyllinga monocephala
India, Ethiopia, Indonesia, South America (country not specified)
EUPHORBIACEAE
Phyllanthus emblica
Phylfanthus niruri
India, Nepal, Tibet, Pakistan

Indonesia, India, West Indies, Brazil
MELIACEAE
Azadirachta indica
India, Fiji, Saudi Arabia, Trinidad
MORACEAE
Morusalba
India, USSR, China, Peru
ROSACEAE
Poterium ancistroides
Spain, Greece, Syria, Israel
APIACEAE
Daucus carota
India, China, England, USA
either cultural contact between the countries or independent discovery. In either case, the conservation of that traditional use indicates a higher probability that the traditional practitioners found the remedy to be effective. Table
3 lists the twenty most widely used traditional antidiabetic
plants. With the notable exception of Kyllinga, all of these
species have already been studied and shown to be active or
have active constituents, and for most of them the identity
of the probable active constituents is known. Several of
these plants will be discussed in detail below.
Seventeen of the twenty most widely used traditional
antidiabetic plants, and many others too, are used in India.
The Indian subcontinent has an extensive indigenous pharmacopoeia, including the Ayurvedic, Unani, and folkloric
medical systems, which has already supplied the world with
such useful drugs as reserpine, from Rauvolfia serpentina,

which is used as an antihypertensive and tranquilizer (Tyler
et al. 1981). Reserpine is also reported to be hypoglycemic
in normal animals and animals made hyperglycemic by pretreatment with epinephrine (Ricci and Ricordati 1955). Indian traditional medicines may very well supply the world
with some new antidiabetic drugs.
Several reviews of plants with known antidiabetic activity or traditional use as antidiabetic remedies, prepared on
a more limited scale than the current work, have been published (Farnsworth and Segelman 1971, Ajgaonkar 1979,
Oliver-Bever and Zahnd 1979, Oliver-Bever 1980, Nagarajan et al. 1982, Mossa 1985, Oliver-Bever 1986, Day and
Bailey 1988, Bailey and Day 1989, Handa et al. 1989, Rah-
o:fOOH
1
"-':::
NH
ccr
1
"-':::
NH
C02H
l,fi
N
11
~O'/COOH
NH2
CI
I~
10
COOH
143
COOH
a
Ih
:::,...1
NH2
12
N+
I
CH
C02
-
C02H
:::,...1
13
OH
14
Fig. 2. Plant growth regulators with hypoglycemic activity.
man and Zaman 1989, Ivorra et al. 1989, Winkelman

1989).
The object of this review is to present a comprehensive
literature review of plants associated with the treatment of
diabetes mellitus, and to discuss with detailed examples
their potential as sources for new antidiabetic drugs. The
primary source of the information on antidiabetic plants
presented here was the NAPRALERT (Natural Products
Alert) computer database of the Program for Collaborative
Research in the Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago.
Hypoglycemic Constituents and

Mechanisms of Action
To understand how plant constituents can be hypoglycemic in animals, it is worthwhile to consider the reasons why
compounds with hypoglycemic activity occur in plants. In
general, discussions of medicinal agents from plants center
on plant secondary metabolites, i.e., non-ubiquitous constituents with no known essential role in the plant's metabolism.
It has been postulated that bioactive plant secondary metabolites may play a role in chemical defense mechanisms
(Ehrlich and Raven 1964, Berenbaum 1983). While the
precise mechanisms that may be involved in chemically mediated coevolution between plants and herbivores or pathogenic organisms are controversial (Strong et al. 1984,
Spencer 1988), it has been suggested that natural selection
would ensure the survival for reproduction of those individuals of a species having the gene coding for production
of a toxin, while individuals without the toxin would be
consumed (Williams et al. 1989).
Most hypoglycemic plant constituents, such as the Catharanthtts alkaloids, might fit in this category, but there are
other rather common plant constituents for which this explanation is not entirely satisfactory. At the cellular and
molecular levels, plants and animals are not very different
in their metabolic processes. Glucose is the metabolic energy source and most important biosynthetic precursor in
plants, so glucose undergoes storage and mobilization
under hormonal control in plants as it does in animals.
Plant growth regulators such as indole-3-acetic acid (Fig. 2,
8) and natural and synthetic analogs such as indole-3-butyric acid, indole-3-propionic acid, L-tryptophan (9), and
p-chlorophenoxyacetic acid (10) , inhibit insulinase in vitro
and are hypoglycemic in vivo in normal rats (Mirsky et al.
1956). Nicotinic acid (11) and anthranilic acid (12) also inhibit insulinase and potentiate simultaneously administered
insulin. An inhibitor of indole-3-acetic acid oxidase from
Phaseo/us vulgaris fruit exocarps also has hypoglycemic activity. The hypoglycemic alkaloid trigonelline (13), from
Trigone//a (oenum-graecum, is a plant growth inhibitor
and produces dormancy.
Salicylic acid (14) is also a plant growth inhibitor and hypoglycemic agent (Oliver- Bever and Zahnd 1979). Thus,
plant metabolism-regulating constituents can also be animal metabolism-regulating agents. The variety of ways in
which this may be possible will become more clear with the
discussion of hypoglycemic mechanisms of action to follow.
Possible active hypoglycemic constituents have been reported for 88 (16 %) of the plants used traditionally as
antidiabetics and 62 (11 "!o) of the other plants screened.
There are more than 200 pure compounds from plant
sources reported to show blood glucose lowering activity.
Table 4 provides a summary of the chemical classes of these
compounds. The wide variety of chemical classes indicates
that a variety of mechanisms must be involved in the lowering of the blood glucose level. Some of these compounds
may have therapeutic potential, while others may produce
hypoglycemia as a side-effect of their toxicity, especially hepatotoxicity.
Some of the compounds reported to be active in vitro or
at high doses in vivo, e.g., ~-sitosterol-D-glucoside (daucosterol, Fig. 3, 16), occur so widely in nature that therapeutic
activity seems unlikely. This could be due to their low concentration in the plant or co-occurrence with complexing
144
Table 4. Hypoglycemic Natural Products

Chemical class
Number active
Chemical class
Number active
Alkaloids
Carbohydrates
Coumarins
Cyanogenic gycosides
F1avonoids
Glycopeptides
Inorganic salts
Iridoids
Lipids
38
Pep tides and amines

Phenolics (simple)
Phenolpropanoids
Steroids
Stilbenes
Sulfur compounds
Terpenoids
Vitamins
Xanthenes
15
4
66
4
1
20
3
4
or counteracting constituents. Some examples of plants

with known active constituents and known mechanisms of
action will be described below to show the range of active
constituents and mechanisms of hypoglycemic action.
Pep tides and Terpenoids from Momordica
The most widely used traditional remedy for diabetes

mellitus is Momordica charantia L. (Cucurbitaceae), common names for which are "bitter gourd," "balsam pear,"
"cundeamor," and "cerasee." The fruit, leaf, and stem have
been used to make an antidiabetic decoction (Rivera 1941,
Rivera 1942, Pons and Stevenson 1943, Ram 1956, Oakes
and Morris 1958, Khan and Burney 1962, Lotlikar and
Rajarama Rao 1966, Jain and Sharma 1967, Morton 1967,
Olaniyi 1975, Ayensu 1978, Halberstein and Saunders
1978, Aslam and Stockley 1979, Gupta et al. 1979, Arnason et al. 1980, Oliver-Bever 1980, Nagarajan et al. 1982,
Morrison and West 1982, Mossa 1985, Bailey et al. 1986,
Singh 1986). In antihyperglycemic bioassays using oral,
subcutaneous, and intravenous dosing of mice, rats, and
rabbits pretreated with anterior pituitary extract, alloxan,
or streptozotocin, and in diabetic humans, it gave different
and often apparently conflicting results (Chatterjee 1964,
Khanna et al. 1981, Mossa 1985, Bailey et al. 1985, Welihinda et al. 1986). In a clinical trial with NIDDM patients,
73 % of the patients showed improved glucose tolerance
with oral administration of M. charantia fruit juice (Weli-
ij
17
2
1
hinda et al. 1986). Some confusion also prevails with hypoglycemic testing in normal animals (Rivera 1942, Pons and
Stevenson 1943, Morrison and West 1982, Karunanayake
et al. 1984, Meir and Yaniv 1985, Welihinda and Karunanayake 1986).
Several active compounds have been isolated from M.
charantia (Fig. 3), and some mechanistic studies have been
done. Khanna et at. (1981) have reported the isolation from
the fruits, seeds, and tissue culture of seedlings, of "polypeptide-p," a 17-amino acid, 166-residue polypeptide
which did not cross-react in an immunoassay for bovine insulin. This peptide was shown to be "insulinomimetic"
when administered subcutaneously in rodent and primate
experimental assays and in a limited clinical trial with both
juvenile- and maturity- onset diabetic patients. A number
of other polypeptides from M. charantia seeds have been
studied in vitro for the insulin-like activities of stimulation
of lipogenesis and inhibition of corticotropin-induced lipolysis. The mechanism was suggested to involve interaction
of the peptides with a-adrenergic or cotticotropin receptors
(Ng et al. 1986).
Another active constituent, charantin, has been isolated
from both M. charantia and M. foetida, and identified as a
mixture of two steroid glycosides: ~-sitosterol-D-glucoside
(15) and 5,25-stigmastadien-3-~-01-D-glucoside (16). Antihyperglycemic activity in alloxan-treated rabbits and depancreatized cats dosed p.o. or i.v. was equivocal, but hypoglycemic activity was observed in normal rabbits, rats,
~H
7
1
2
HO
OH
15
Fig. 3. Steroid glycosides of Momordica charantia reported to be hypoglycemic.
16

and cats dosed p.o., i.p., or i.v. (Lotlikar and Rajarama Rao
1966). Studies performed in vitro with M. charantia fruit
extracts indicated a significant enhancement of glucose uptake in muscle tissue and of glycogen accumulation in muscle and hepatic tissue, but no effect on glucose uptake or
triglyceride synthesis in adipose tissue (Meir and Yaniv
1985, Welihinda and Karunanayake 1986). Inhibition of
glucose uptake by intestinal fragments was also observed
and attributed to a glycosidic constituent of the fruit extract (Meir and Yaniv 1985). Thus, there appear to be constituents of M. charantia with both pancreatic and extrapancreatic effects with therapeutic potential for diabetic
patients. Caution is advised, however, because a mildly toxic lectin has been reported from the seeds and outer rind of
the fruits, which is capable of interfering with protein synthesis in the intestinal wall (Lampe and McCann 1985).
Alkaloids from Catharanthus
The Madagascar periwinkle (Catharanthus roseus [L.] G.
Don, Apocynaceae), is another widely used traditional remedy for diabetes, and a proprietary preparation, Vinculin,
was marketed in England as a "treatment" for diabetes.
Pharmacological studies have been conducted on periwinkles since the 1920's, and while two studies of leaf aqueous
extracts administered orally to rabbits (Asthana and Misra
1979) and dogs (Morrison and West 1982) reported a hypoglycemic response, many other experiments with a variety of laboratory animals and limited clinical studies have
given negative or at best equivocal results (Noble et al.
1958, Farnsworth 1961, Svoboda et al. 1959 and 1964,
Farnsworth and Segelman 1971, Swanston-Flatt et al.
1989).
Despite these disappointing results, Svoboda et al. (1964)
tested for hypoglycemic activity a number of alkaloids (Fig.
4) isolated from C. roseus during an investigation of the
plant's oncolytic activity, which was discovered by Noble et
al. (1958) while investigating the plant's reputed antidiabetic activity. Hypoglycemic activity was observed for catharan thine (17), leurosine (18), lochnerine (19), tetrahydroalstonine (20), vindoline (21), and vindolinine (22). Administered orally in a dose of 100 mg/kg, leurosine sulfate and
vindolinine hydrochloride were more hypoglycemic than
tolbutamide, the commercial antidiabetic sulfonylurea used
as a positive control (Svoboda et al. 1964). Svoboda et al.
(1964) suggested that toxicity of crude extracts and fractions (e.g., several of the alkaloids are potent cytotoxic
agents) may have made their experimental antidiabetic verification difficult, but that further study of C. roseus as a
natural antidiabetic agent would be worthwhile.
Some progress has been made in this direction. The Catharanthus and Vinca alkaloids, vincamine (23) and (-)-eburnamonine (24), have been shown to induce an extensive decrease in rat brain tissue glucose, a concomitant increase in
lactate and pyruvate concentrations and the lactateJpyru-
145
vate ratio, and an increase in ATP contents and energy

charge potential (Benzi et al. 1984). Tetrahydroalstonine
(20), administered orally in rats with alloxan-induced hyperglycemia, produced a triphasic response of a rapid-onset
hypoglycemia, a recovery period from 2-12 hours posttreatment, and then a prolonged hypoglycemic effect lasting more than 48 hours post-treatment (Kocialski et al.
1972).
In an in vitro study of the mechanism of action of the
quinoline derivatives, quinolate and 3-mercaptopicolinate,
Snell (1979) reported that hepatic gluconeogenesis from
lactate or alanine, and the release from muscle of alanine, is
inhibited through inhibition of cytosolic and mitochondrial
phosphoenolpyruvate carboxykinase. The mechanism involves a direct effect which is facilitated by complex formation between the agent and Fe2+ or Mn2+, an inhibitory action on the ferroactivator-mediated Fe 2+ activation of cytosolic phosphoenolpyruvate carboxykinase, and indirect effects by lowering of cytosolic oxaloacetate concentrations
through blocking the translocation of anions such as 2- oxoglutarate from mitochondria, and inhibiting cytosolic
aspartate aminotransferase.
Certainly the active alkaloids of Catharanthus could
serve as models for the development of new antidiabetic
drugs. Eleven indolizine alkaloids, synthesized as analogs
of vincarnine, vindoline, and vindolinine, were tested for
oral hypoglycemic activity in fasted rats, but the best was
only one third as active as tolbutamide (De and Saha 1975).
Sulfur Compounds from Allium
The hypoglycemic principles of onion (Allium cepa L.,
Liliaceae) and garlic (A. sativum L.) are the sulfur-containing compounds, allyl propyl disulfide (25 in Fig. 5) and diallyl disulfide oxide (allicin, 26). Active in normal and alloxan-diabetic animals and patients with NIDDM, but not
pancreatectomized animals, they are believed to act by
competing with insulin, which has a disulfide linkage, for
endogenous sulfhydryl-rich insulin-inactivating compounds (Augusti et al. 1974, Oliver-Bever and Zahnd
1979). However, an oral feeding study of garlic bulbs given
to normal or streptozotocin-diabetic mice showed reduced
hyperphagia and polydipsia but no effect on hyperglycemia
or hypoinsulinemia (Swanston-Flatt et al. 1990).
Inorganic Ions from Atriplex
The saltbush (Atriplex halimus L., Chenopodiaceae) was
investigated for antidiabetic activity after sand rats (Psammomys obesus), that in nature feed extensively on the
leaves of this plant, developed diabetic symptoms after being captured and fed laboratory rat chow or fresh vegetables. The sand rats have a genetic predisposition to diabetes
that seems to be prevented by the presence of chromium,
manganese, and magnesium salts in the saltbush leaves.
146
17
18
H
19
20
21
22
~N
CXXJ
p
23
CH CH
2
3
24
Fig. 4. Hypoglycemic alkaloids of Catharanthus roseus.
Studies of the leaf ash and chromium in vitro showed a potentiation of insulin-stimulated glucose utilization by epididymal fat cells of chromium deficient rats. The mechanism may involve Cr2+ inactivation of an insulin-inactivating enzyme (Aharonson et al. 1969, Oliver-Bever and
Zahnd 1979). The reputed hypoglycemic activity of the
"glucose- tolerance factor" of brewer's yeast, Saccharomyces cerevisiae, which has been attributed to trivalent chromium (CrJ +), was contradicted by long-term feeding studies
in genetically diabetic mice, in which no beneficial t;ffect
was seen (Flatt et al. 1989). However, chromium does potentiate the action of insulin in vitro and in vivo. Maximal in
vitro activity requires mineral complexation, e.g. a chromium-nicotinic acid complex. Clinical trial results were vari-
able but the majority of patients showed an improved efficiency of insulin. (Mertz 1993).
Chronic administration of magnesium salts has also been
shown to be beneficial in the treatment of NIDDM. Hypomagnesemia is a common finding in diabetic subjects. Magnesium is a necessary cofactor for many enzymes and is involved in protein synthesis. Treatment with magnesium
salts resulted in a net increase in acute insulin response and
the rate of glucose disappearance after glucose loading
(Paolisso et al. 1989, White and Campbell 1993).
Other minerals may also playa role in diabetes pathogenesis and therapy. The protein tyrosine kinase associated
with the insulin receptor has been shown to be Mn2+dependent (Reddy and Kahn 1988). Vanadium is another trace
147
2S
CH 2=CH-CH 2-S(....O)-S-CH 2-CH=CH 2
27
26
Fig. 5. Hypoglycemic sulfur compounds from Allium spp.
mineral whose salts have insulin-like properties in animal

models of insulinopenia or insulin resistance in vitro and in
vivo, due to stimulation of glucose metabolism. Like most
dietary trace minerals vanadium is toxic in excess so its
therapeutic potential is being investigated carefully (Brichard et al. 1991).
28
(CH 3hN+CH 2 CH(NHCOCH 3)CH 2 COO-
Amino Acids from Blighia

Ingestion of unripe akee fruit (Blighia sapida Koenig, Sapindaceae) causes the often fatal disorder " \-omiting sickness" in Jamaica. The emetic constituents were discovered
to be the cyclopropanoid amino acid, hypoglycin A (27 in
Fig. 6), and its y-L-glutamyl dipeptide, hypoglycin B (28).
which are also potent hypoglycemics. They appear to act by
inhibiting ~-oxidase enzymes, thus blocking oxidation of
long-chain fatty acids. Since the fatty acids are no longer
available as an energy source, hepatic glycolysis is stimulated to provide an alternate source, and the increased utilization of glucose brings about a fall in blood glucose levels.
Hypoglycin A is twice as potent a hypoglycemic as hypoglycin B; the latter is also teratogenic, so these compounds
are too toxic to be used therapeutically, though they may
provide models for the development of new hypoglycemic
agents (Feng and Patrick 1958, von Holt et al. 1966, Tanaka et al. 1972, Oliver-Bever and Zahnd 1979).
In order to find a more specific inhibitor of free fatty acid
oxidation, Kanamaru et al. (1985) screened microbial metabolites for substances that would inhibit the oxidation of
long-chain fatty acids in rat liver mitochondria. This research led to the discovery of the ~-aminobetaines, emericedin (29) and its more potent synthetic derivative emeriamine (30), from the fungus Emericella quadrilineata IFO
5859 (Trichocomaceae). Emeriamine was shown to be a potent and specific inhibitor of carnitine palmitoyltransferase
I, and both compounds had dose-dependent oral hypoglycemic and anti ketogenic activities in fasted normal, streptozotocin-diabetic, and genetically obese (Zucker) rats.
Guanidines from Galega

Seeds of the traditional antidiabetic plant. "goat's rue:'
(Galega officinalis L., Fabaceae) contain the guanidine derivative, galegine (31 in Fig. 7). Like synthetic biguanide
hypoglycemics (6, 7), galegine blocks succinic dehydroge-
29
(CH 3hN'CH 2CH(NH 2)CH 2COO-
30
Fig. 6. Inhibitors fo fatty acid oxidation.
nase and cytochrome oxidase, thus increasing anaerobic

glycolysis and decreasing gluconeogenesis, resulting in enhanced glucose uptake and hypoglycemia. Biguanides are
also known to inhibit glucose absorption from the intestine
(Oliver-Bever and Zahnd 1979).
Vitamins, Coumarins, and Steroids from Trigonella

Fenugreek (TrigonelLa foenum-graecum L.), seeds contain a number of hypoglycemic principles, although an oral
feeding study performed with normal and streptozotocindiabetic mice showed no significant effect of seed consumption on basal glucose and insulin, insulin-induced hypoglycemia, glycosylated hemoglobin, or pancreatic insulin concentration (Swanston-Flatt et al. 1989). Trigonelline (Fig.
2: 13), which is the N-methyl derivative and main human
metabolite of the vitamin nicotinic acid (niacin, 11), has a
weak and transient hypoglycemic effect when administered
orally to diabetic patients. It acts by slowing the metabolism of nicotinic acid, also present in Trigonella, which is
known to increase glucose uptake from the blood and its
subsequent oxidation, if administered orally. Nicotinic acid
is hyperglycemic if administered parenterally, by means of
impairment of carbohydrate utilization (Mishkinsky et al.
1967, Shani et al. 1974). Taken orally, nicotinic acid is converted in the body into nicotinamide, which is an inhibitor
of the enzyme poly(ADP-ribose) synthetase, responsible for
the depletion of NAD from pancreatic ~-cells, and is also a
potent hydroxyl-radical scavenger, by which mechanisms
148

HN=<
NH
NH
2
HO
~=<
31
32
Fig. 7. Comparison of the structures of galegine and metformin.
nicotinamide can prevent the ~-cell toxicity of streptozotocin and alloxan (Ledoux et al. 1988). Free-oxygen radicals
are important mediators of ~-cell destruction in IDDM,
and nicotinamide's antioxidant activity has been shown to
have some effect on preventing IDDM in high-risk individuals and has a slight effect on residual insulin secretion in
newly diagnosed patients. Other antioxidants have been
tested in animal models with results suggesting prevention
of diabetes (Ludvigsson 1993).
Vitamin E (a-tocopherol, 32 in Fig. 8), which occurs in
seed oils and green leafy vegetables, has been shown at doses of 600-1200 mg daily to reduce the levels of glycosylated hemoglobin in diabetic subjects independently of changes in plasma glucose, which may help reduce the incidence
of diabetic complications (Ozden et al. 1989, Ceriello
1991).
Coumarin (33), another constituent of Trigonella, is profoundly hypoglycemic in normal and alloxan-diabetic rats
(Shani et al. 1974). The mechanism for this observation
probably involves hepatotoxicity. Coumarin is hepatotoxic
in rats and dogs, where it is metabolized through 3-hydroxycoumarin to reactive quinone metabolites that bind
covalently to microsomal proteins. In humans and other
primates, however, coumarin is metabolized through 7-hydroxycoumarin to a glucuronide conjugate that is rapidly
excreted, and no hepatotoxicity occurs (Cohen 1979). S_copoletin (34), another coumarin constituent of Trigonella,
exerted borderline hypoglycemic effects in normal and alloxan-diabetic rats at high doses (Shani et al. 1974). Fenugreekine (35), a steroidal sapogenin-peptide ester, is another hypoglycemic constituent (Ghosal et al. 1974).
Complex Carbohydrates and Postprandial
Blood Glucose
Seeds of a number of other members of the Fabaceae are

used traditionally to treat diabetes. In addition to direct hypoglycemic effects of their constituents, dietary effects are
also important. Clinical studies of high legume diets
showed improvement in many of the indices of blood glucose control, especially postprandial levels. Beans are high
in complex carbohydrates which are more slowly digested
than other types of starch. Non-cellulosic types of dietary
fiber such as carob gum and guar gum, high-molecularweight galactomannans from Ceratonia siliqua L. and Cyamopsis tetragonoloba (L.) Taub . respectively, slow intestinal absorption of glucose by slowing gastric emptying and
eel
o
33
34
3S
Fig. 8. Some antidiabetic constituents of Trigonella foenum-graecum.
by thickening the unstirred water layer adjacent to the intestinal villi (Leeds 1981, Karlstrom et al. 1987). Modification of the physical and chemical characteristics of the intestinal contents by leguminous gums might also modify
the release of gastrointestinal hormones which influence insulin secretion and gastrointestinal motility (Forestieri et al.
1989). Provision of purified guar fiber as tablets taken with
meals significantly reduced low-density lipoprotein cholesterollevels but did not improve excessive postprandial glycemia in ~DDM patients in whom near-normal fasting
plasma glucose levels had been obtained with diet, sulfonylurea, or human ultralente insulin therapy (Holman et al.
1987). Patient compliance may be a problem with pure
guar gum due to its unpalatability and tendency to cause
abdominal distension and diarrhea, but incorporation into
high-carbohydrate foods has been shown to provide even
more effective blunting of the postprandial glycemic profile
without gastric distress (Briani et al. 1987).
Some legumes also contain low levels of lectins, which if
incompletely destroyed by inadequate cooking, might accelerate intestinal motility and increase mucus secretion,
thus modifying absorption of glucose (Leeds 1981). The
antidiabetic activities of a number of other plant gums were
attributed to inhibition of gluconeogenesis and stimulation
of peripheral glucose utilization, not to interference with
intestinal absorption of glucose (AI-Awadi and Gumaa
1987). Some structure-activity relationships of hypoglycemic plant mucilages have been studied (Tomoda et al.
1987). Intestinal bacterial fermentation of leguminous olig-
~HOHN~3
2OH
HO
HO
HO
HO
o~20H
HO
HO
2OH
HO
HO
mulberry (Morus alba L., Moraceae) root bark and also

leaves of Jacobinia (Acanthaceae) and cultures of Bacillus
and Streptomyces, inhibits intestinal a-glucosidase potently
but only weakly inhibits l3-glucosidase, glucoamylase, and
a-amylase (Yoshikuni 1988). Miglitol (39), prepared semisynthetically from moranoline, is an a-glucosidase inhibitor which, unlike acarbose, is absorbable from the gastrointestinal tract. It may exert inhibitory effects on nonintestinal a-glucosidase present in various cell types, and has been
clinically evaluated as a hypoglycemic agent in both IDDM
and NIDDM (Reuser and Wisselaar 1994).
OH
36
Hypoglycemic Glycans
~r~~H
HO~~
HO
OH
OH
37
149
38
39
Fig. 9. Hypoglycemic intestinal enzyme inhibitors.
osaccharides and fiber, in addition to producing a feeling of

satiety that might aid in compliance with a fixed diet, produces short-chain fatty acids which are then absorbed and
affect metabolic processes relevant to diabetic control, such
as hepatic gluconeogenesis (Leeds 1981).
A microbial product, acarbose (36 in Fig. 9), isolated
from strains of Actinoplanes sp. (in the order Actinomycetales) (Hillebrand 1987), is known to inhibit the intestinal
a-glucosidases, y-amylase, sucrase, and maltase. This action reduces the release of glucose from carbohydrates, resulting in a dose-related delay in, or reduction of, the postprandial increase in blood glucose and triglycerides, diminished prevalence of diabetic nephropathy, as well as increased insulin binding in muscle (Hillebrand 1987, Yoshikuni 1988, Le Marchand-Brustel et al. 1990, Hanefield et
al. 1991).
Castanospermine (37), an indolizidine alkaloid isolated
from Castanospermum australe A. Cunn. (Fabaceae), is another example of an intestinal enzyme inhibitor with hypoglycemic activity. Structurally, castanospermine shares similarities with the pyranose form of glucose in the orientation of its hydroxyl groups. It blocks the hyperglycemic response to oral doses of sucrose through inhibition of disaccharase, but does not reduce glucose-induced hyperglycemia (Rhinehart et al. 1987). Moranoline (38), isolated from
Hikino's research group (Hikino et al. 1985a-c, 1986a-c,

1988, Konno et al. 1985a-e, Takahashi et al. 1985a,b,
1986, Tomoda et al. 1987, 1990) has isolated a variety of
glucans, peptidoglucans, and heteroglycans from plants
used in oriental traditional medicine. These complex carbohydrates, with molecular weights ranging from approximately 1000 - >10,000,000 amu, were shown to have remarkable hypoglycemic activity when administered intraperitoneally (i.p.) to normal, alloxan-hyperglycemic, and
spontaneously diabetic mice.
The mechanism of action of the glucan aconitan A, from
Aconitum carmichaeli Debeaux (Ranunculaceae), involves
significant potentiation of the activity of hepatic phosphofructokinase. Acceleration of glycolysis in the liver was accompanied by some increase in hepatic total glycogen synthetase, but liver glycogen content and plasma and liver
cholesterol and triglyceride contents were unchanged, indicating that the conversion of glucose into glycogen or lipids
does not contribute to the hypoglycemic activity of aconitan A. Plasma insulin levels and insulin binding to isolated
adipocytes also were unaffected. Stimulation of glucose uptake and metabolism in small intestine tissues was observed. Thus, stimulation of glucose utilization in the liver
and peripheral tissues is the main mechanism for the hypoglycemic activity of aconitan A (Hikino et al. 1989a).
Ganoderan B, a glycan from Ganoderma lucidum Karsten (Polyporaceae), increases the plasma insulin level in
normal and glucose-loaded mice, increases the activities of
hepatic glucokinase, phosphofructokinase, and glucose-6phosphate dehydrogenase, decreases the activities of hepatic glucose-6-phosphatase and glycogen synthetase, and
reduces hepatic glycogen content. The observed stimulation of glucose metabolism in a homogenate of the
small intestine suggests that acceleration of glucose utilization may also occur in peripheral tissues (Hikino et al.
1989b).
Panaxans A-E, glycans of ginseng (Panax ginseng CA.
Meyer, Araliaceae), show different mechanisms of action
despite their similar structures. Panaxans A and B stimulate
hepatic glucose utilization by increasing the activity of glucose-6-phosphate dehydrogenase, phosphorylase-a, and
150
40
Fig. 10. Sapogenin of ginsenosides and panaxosides: protopanaxadiol Rj =H, ptotopanaxatriol Rj =OH; sugars in glycosides are
attached to oxygens at R,-R j
phosphofructokinase. Panaxan A decreases the activity of

glucose-6-phosphatase but does not affect hepatic glycogen content. Panaxan B has no effect on glucose-6-phosphatase but decreases glycogen synthetase activity and hepatic glycogen content. Panaxan A does not affect plasma
insulin levels and insulin sensitivity, but panaxan B elevates
the plasma insulin level by potentiating insulin secretion
from pancreatic islets and enhances insulin sensitivity by
increasing insulin binding to receptors (Suzuki et al.
1989a,b).
Ginseng contains a number of other hypoglycemic constituents, with different mechanisms of action. Adenosine
was isolated from a water extract of the rhizomes by bioassay-guided fractionation, and was shown to enhance lipogenesis and cyclic adenosine monophosphate (cAMP) accumulation in adipocytes, which possess specific adenosine
receptors. Some of the sterol glycosi-des known as ginsenosides (40 in Fig. 10) inhibited adrenocorticotropin-induced
lipolysis and at the same doses suppressed insulin-stimulated lipogenesis, while others stimulated the release of insulin
from cultured islets (Waki et al. 1982. Ng and Yeung
1985).
Plant Constituents that Modulate Intracellular SecondMessengers
Pancreatic ~-cell membranes possess adenosine triphosphate (ATP)-sensitive K+ channels which, in the absence of
glucose, allow an efflux of K+ to contribute a hyperpolarizing membrane current that maintains the hyperpolarized
resting membrane potential of the cell. Metabolites of glucose and amino acids inhibit this channel. causing a reduction in the hyperpolarizing current, which leads to ~-cell_
depolarization and voltage-dependent Ca~+ uptake. Binding of Ca2+ to calmodulin results in microfilament contraction, resulting in exocytosis of insulin from storage granules. Intracellular ATP is believed to have a second-messenger role in inhibiting the K+ channel by almost 99 %, thus
making the ~-cell very sensitive to changes in channel activity (Cook et al. 1988, Misler et al. 19891. Tolbutamide (2)
specifically mimics the effects of glucose stimulation, depo-
larizing the ~-cells by inhibiting the ATP-sensitive K+ channel, which has been suggested to be the ~-cell receptor for
sulfonylureas. The alkaloid quinine (41 in Fig. 11) is also a
potent blocker of this channel, although, unlike the sulfonylureas, it also blocks Ca2+-activated K+ channels (Cook
and Ikeuchi 1989).
Intracellular cAMP also acts as a second-messenger in the
~-cells. Increasing the intracellular cAMP concentration
potentiates cholecystokinin- and glucose-stimulated insulin
release. The mechanism involves synergistic action with the
influx of Ca 2+ that occurs as a consequence of the glucose
metabolite-induced increase in intracellular K+ (Hill et al.
1987). The physiological actions of glucagon result from
stimulation of cAMP synthesis, which in pancreatic ~-cells
forms part of the pancreatic hormone regulatory mechanism (Lamer 1980). The role of second-messengers in insulin action has been reviewed by Saltiel (1990).
The most famous plant product for the stimulation of
intracellular cAMP is forskolin (42), a diterpene from Coleus forskohlii (Poir.) Briquet (Lamiaceae). It is an adenylate
cyclase activator which increases intracellular cAMP by
stimulating its biosynthesis. Theophylline (43) and other
methylxanthenes from Camellia sinensis (L.) Kuntze (Theaceae) and flex guayusa Loesner (Aquifoliaceae), and papaverine (44) from Papaver somniferum L. (Papaveraceae), are
phosphodiesterase inhibitors which increase intracellular
cAMP by preventing its breakdown (Gearien and Mede
1981, Hill et al. 1987, Zawalich et al. 1988). Theophylline
is orally hypoglycemic when administered chronically to
normal rats, but this in vivo effect was not attributed to its
phosphodiesterase inhibition, but rather due to its induction of intracellular Cal. efflux. Increased extracellular
Ca l + might enhance calcium-stimulated ATPases, which
would result in decreased cellular ATP levels, enhanced lipolysis, and reduced glycogenolysis. This effect is also seen
with administration of caffeine (45) (Tobin et al. 1976).
Sodium salicylate (salt of 14) inhibits cyclooxygenase,
thus preventing the metabolic cascade from arachidonic acid to the prostaglandins. Inhibition of ~-cell PGE2 synthesis
increases glucose-induced insulin secretion because this
prostaglandin binds to specific ~-cell receptors that are coupled to regulatory components that inhibit adenyl ate cyclase. Inhibition of this enzyme would lead to a decrease in
intracellular cAMP (Robertson 1988). Additionally, arachidonic acid (46) itself is an insulin secretagogue, acting to
mobilize Ca 2+, increasing its free cytosolic concentration,
and to activate protein kinase C (Metz 1988).
Carbohydrate components of the diet stimulate the release of the hormone "gastric inhibitory polypeptide,"
which is thought to influence insulin secretion by elevating
islet ~-cell cAMP levels. The activity of cAMP is also synergized by phosphoinositide-derived second-messenger molecules generated during the phospholipase C-mediated
cleavage of membrane phospholipids in the ~-cell. This hydrolysis is thought to be activated by the interaction of ex-
151
HO"
"',,=
0
"
OH
"",
'
H
OH
OCOCH 3
41
42
43
44
45
46
"l?)::::'&
~
I '"
OH
OH
HO
OH
HO
OH
OH
OH
OH
OH
47
48
OH
49
50
Fig. 11. Modulators of intracellular second-messenger systems.
tracellular hormones and agonists with a specific membrane receptor (Zawalich 1988).
The flavonoid, (-)-epicatechin (47), isolated as the active
principle of the traditional antidiabetic plant Pterocarptls
marsupium Roxb. (Fabaceae), has been shown to cause an
ATP-dependent enhancement of glucose-stimulated insulin
secretion from isolated islets, and to cause a rise in islet insulin content in vivo in rats. Inhibition of cAMP phosphodiesterase and stimulation of insulin biosynthesis were suggested to be the mechanisms for the observed effects (Hii
and Howell 1984). The flavonoids quercetin (48) and myricetin (49) have also been reported to be hypoglycemic
(Rahman and Zaman 1989), but they are known to be potent inhibitors of protein tyrosine kinase (Geahlen et al.
1989), the activity of which is essential in the post-receptorbinding activity of insulin.
When insulin binds to the extracellular a-subunit of its

heterodimeric cell surface receptor, the insulin-receptor
complexes aggregate along the plasma membrane and are
then internalized rapidly. Activation of a Mn 2 +-dependent
protein tyrosine kinase in the transmembrane ~-subunit ensues, resulting in phosphorylation of the receptor and other
proteins with phosphate groups from ATP (Reddy and
Kahn 1988). Activation of a phosphatidylinositol-specific
phospholipase C leads to hydrolysis of a membrane glycan
phosphoinositide. This produces a cyclic inositol phosphate-glucosamine second-messenger that activates phosphodiesterase, decreasing intracellular cAMP, and also produces diacylglycerol, which activates protein kinase C (Saltiel et al. 1986). Protein kinase C regulates a number of enzymes and the insulin receptor through phosphorylation
(van de Werve 1985a).
152
Some tumor-promoting phorbol esters, such as 12-0-tetradecanoylphorbol-13-acetate (TPA, 50), share structural
similarities with diacylglycerol, and are potent activators of
protein kinase C (van de Werve et al. 1985). Phorbol esters
are diterpenes isolated from species of Euphorbia and a few
other genera of the Euphorbiaceae (Kinghorn 1983), 30
species of which have been associated with the treatment of
diabetes. Phorbol esters have been reported to have a number of insulinomimetic effects, including stimulation of glucose transport, lipogenesis, and amino acid uptake. However, they may reduce insulin receptor affinity for insulin,
insulin stimulation of glucose transport and lipogenesis,
and basal glycogen synthesis (Sowell et al. 1988). It has
been suggested that phorbol ester-stimulated serine phosphorylation of insulin receptors may be associated with a
decrease in the affinity of the receptor for insulin and decreased receptor tyrosine kinase activity, although conflicting results have been reported (van de Werve et al. 1985a,
Obermaier et al. 1987, Sowell et al. 1988). Ishizuka et al.
(1991) found that phorbol esters, glucose, and insulin
translocatively activate protein kinase C, resulting in a subsequent down-regulation of protein kinase C and insulinstimulated glucose uptake in adipocytes. This contributes
to impaired responsiveness of the glucose transport system
after prolonged insulin and/or glucose exposure. Phorbol
esters can inhibit ai-adrenergic stimulation of glucose production by inhibiting phosphorylase activity, also through
their effect on protein kinase C (van de Werve et al. 1985b).
They can also inhibit glucagon-stimulated adenylate cyclase, but the metabolic significance of this is much less
than that of their inhibition of ai-adrenergic effects (Garda- Sainz et al. 1985). Tumor promotion may also be
explained by phorbol ester activation of protein kinase C
(van de Werve et al. 1985a).
Plant Hypoglycemics Acting by Adrenergic Effects
In addition to the ai-adrenergic inhibition described

above for tumor-promoting phorbol esters, a number alkaloids are known to affect blood glucose levels by a similar
mechanism. In normal patients, there is no effect of a-, ~-,
or a+~-blockade on the slope of glucose-potentiated insulin
secretion. In patients with NIDDM, only selective a-adrenergic blockade increases glucose-potentiated insulin secretion, through both a decrease in an endogenous overactive
a-adrenergic stimulation and an increase in synaptic cleft
norepinephrine levels, which results in an increase in islet ~
adrenergic stimulation. Thus, a chronic decrease in islet aadrenergic stimulation may be a useful adjunct to NIDDM
management (Broadstone et al. 1987).
Ergot alkaloids, occurring in fungi such as Claviceps pttrpurea (Fries) Tulasne (Hypocreaceae) and at least one
group of higher plants, Rivea corymbosa (L.) Hallier f. and
closely related Ipomoea and Argyreia species (Convolvulaceae), are a-adrenergic blockers which inhibit epinephrine-
induced hepatic glycogenolysis and hyperglycemia, but not

glycogenolysis in skeletal muscle. These effects are not correlated with their well-known smooth muscle effects, and
may not be due to a specific a-receptor effect (Weiner
1980). Dihydroergotamine (51 in Fig. 12) and yohimbine
(52), another a-adrenergic blocking alkaloid from Pausinystalia yohimbe (K. Schumann) Pierre (Rubiaceae), prevented epinephrine-induced inhibition of insulin release,
but not diazoxide-induced inhibition (Henquin et al. 1982).
However, yohimbine is also a monoamine oxidase inhibitor
and is contraindicated for patients with diabetes (Tyler et
al. 1993).
Beta-adrenergic blocking agents reduce the hyperglycemic response to epinephrine by blocking its stimulation of
cAMP production. Epinephrine-induced glycogenolysis in
heart and skeletal muscle and lipolysis in isolated rat adipocytes is inhibited. By these mechanisms, the non-selective
~-adrenergic blocking agent, propranolol, slows the postinsulin recovery of glucose concentration and prevents the
usual rebound of plasma glycerol, while not affecting plasma glucose or insulin concentrations in normal individuals,
or the rate or magnitude of the fall of plasma glucose after
insulin (Weiner 1980). Beta-adrenergic blocking agents can
also reduce insulin resistance caused by ~-adrenergic stimulation (Attvall et al. 1987). Kimura et al. (1988) suggested
a possible ~-adrenergic blockade mechanism for the hypoglycemic activity of an orally-administered aqueous extract
of Ganoderma lucidum (Leyss. ex Fr.) P. Karst (Ganodermataceae).
Reserpine (53), from Rauvolfia serpentina (L.) Benth. ex
Kurz (Apocynaceae), is an adrenergic blocking agent that
causes intracellular depletion of catecholamines and serotonin. Uptake of catecholamines is also antagonized by inhibition of the ATP-Mg2+-dependent uptake mechanism of
the chromaffin granule membrane. A transient sympathomimetic effect is seen only after parenteral administration of relatively large doses; pharmacological effects of the
released catecholamines are minimal unless monoamine
oxidase has been inhibited (Weiner 1980). Reserpine enhanced the hypoglycemic effect of insulin and the hyperglycemic effect of epinephrine in normal subjects. In glucose
tolerance tests it inhibited the hyperglycemic response, even
in diabetic patients (Ricci and Ricordati 1955). However,
hypoglycemia is not reported as a significant side-effect of
reserpine, nor are interactions with other hypoglycemic
drugs listed (American Pharmaceutical Association 1976).
Photosensitizers and IDDM
Insulin-dependent diabetes may arise through T-Iymphocyte mediated ~-cell destruction. One possible novel approach to interrupting this pathogenic process is photopheresis, whereby lymphocytes would be treated with a
photosensitizer such as 8-methoxypsoralen (54 in Fig. 13)
and UVA radiation to cause a change in the antigenicity of
153
f'o~oAo
f)I
OCH 3
S4
OH
S2
SI
S3
Fig. 12. Adrenergic-blocking hypoglycemic alkaloids.
the treated lymphocytes. This is postulated to cause a vaccination-like effect in the patient when they are retransfused at repeated intervals into the patient. This has proved
effective in other autoimmune diseases and is now in clinical trials for IDDM (Ludvigsson 1993). Photosensitizers
have been isolated from more than 30 flowering plant families (both monocots and dicots) and represent a wide range
of chemical classes including: polyacetylenes, thiophenes,
lignans, porphyrins, quinones, chromenes, benzofurans, furoflavonoids, furocoumarins (e.g. 54), furochromones, furoquinoline alkaloids, and (3-carboline alkaloids (Downum
1986, Hudson 1990). A thiophene such as a-terthienyl (55)
may have an advantage over 8-methoxypsoralen in these
applications because of its lack of genotoxicity (MacRae et
al. 1980, Tuveson et al. 1986). Structure-activity relationship studies of thiophenes have shown the possibility of
achieving some cell or organism specificity despite the general mechanism of action involving singlet oxygen generation (Maries et aI. 1992).
Plant Hypoglycemic Drug Screening

Methodology
Scientific investigation of traditional medicines, as in the

examples provided above, has resulted in the discovery of a
number of promising leads for new antidiabetic agents.
Modern drug discovery requires a systematic approach to
optimize time and resource use for testing the maximum
number of samples in bioassays which hopefully are predictive for therapeutic efficacy. These approaches to bioassayguided antidiabetic drug discovery can be divided into two
main classes: in vivo and in vitro techniques.
5S
Fig. 13. Plant-derived photosensitizers.
In Vivo Techniques
Techniques for the study of hypoglycemic activity in vivo

employ animals with normoglycemia or induced hyperglycemia, as well as diabetic humans. Methods used to experimentally induce hyperglycemia include loading with glucose or cholesterol, treatment with drugs such as alloxan,
streptozotocin, 2,4-dinitrophenol, and diazoxide, hormones such as epinephrine, glucagon, corticotropin, somatotropin, and anterior pituitary extract, and surgical procedures such as partial or full pancreatectomy. Genetically
obese and hyperglycemic animals such as Zucker falfa rats
(e.g. Rosen et aI. 1986, Young et a!. 1991), yellow KK mice
(e.g. Kanamaru et al. 1985), spontaneously diabetic mice of
strain C57BUKsj-db/db (Suzuki and Hikino 1989), and
sand rats (Psammomys obesus) (e.g. Aharonson et al.
1969) have also been used.
The most popular in vivo models for diabetes are rodents
treated with alloxan (56 in Fig. 14) or streptozotocin (57).
The history and mechanism of alloxan, a pyrimidine derivative, has been reviewed by Lenzen and Panten (1988), who
point out that, while it is a very selective toxin of pancreatic (3-cells through its inhibition of glucokinase, thus making
it a good model for diabetes mellitus, there are a number of
problems with its use. Alloxan's chemical instability, rapid
metabolism, thiol reactivity, and effects of factors such as
diet, age, and species, have made it almost impossible to establish a clear relationship between the dose of alloxan and
its effective concentration in the pancreas. Thus it is difficult to be certain of the extent of (3-cell inhibition and necrosis from a particular dose of alloxan.
Streptozotocin, also known as streptozocin, is a natural
nitrosourea glycoside isolated from Streptomyces achromogenes, which also causes degeneration of pancreatic (3-cells.
A single dose in the neonatal rat can produce an experimental model of NIDDM, characterized by deficient insulin
biosynthesis and release in response to glucose and diminished pancreatic insulin content. There is a selective lack of
sensitivity of the l3-cells to glucose and glyceraldehyde, but
continued response to other secretagogues. The insensitivity of the islets to glucose is associated with deficient islet
glucose metabolism, probably due to a streptozotocin-induced alteration in islet mitochondrial function (Portha et
al. 1988). Looking at adipocyte insulin binding and glucose
transport, however, Fantus et a!. (1987) concluded that the
neonatal streptozotocin-injected rat model did not provide
a complete representation of human NIDDM.
154
;;~;
H~OH
NHCON(NO)CH
S6
S7
Fig. 14. Commonly used drugs for creating models of diabetes

mellitus.
For a model of IDDM where there is a total absence of pcell function, pancreatectomy is sometimes used. However,
at least in rabbits, due to the extended distribution of the
pancreas and its close association with the duodenum, a total pancreatectomy may not be feasible or totally successful
if attempted. An in vivo bioassay employing surgical removal of the pancreas and a complementary injection of alloxan was shown to give blood glucose values significantly
different from those of animals with only surgical intervention (Ibanez-Camacho et al. 1983).
A further complication of in vivo hypoglycemic screening
was described during an investigation of aqueous extracts
of Tecoma stans Juss. (Bignoniaceae). Although initial in vivo hypoglycemic screening of the extract gave inconclusive
results, chemical investigations resulted in the isolation of
two monoterpene alkaloids, tecomanine (58 in Fig. 15) and
tecostanine (59), which were shown to be hypoglycemic
when administered i.v. or p.o. in rabbits (Hammouda et al.
1964, Hammouda and Amer 1966). The crude aqueous extract of the plant, when administered i.v. to fasted dogs or
i.p. to glucose-loaded rats, produces a sharp but transient
(10 min) fall of arterial blood pressure and a transient
(180 min) but significant hyperglycemia due to induction of
hepatic glycogenolysis and subsequent elicitation of insulin
release. This was followed by a slight hypoglycemia with a
maximum decrease of the blood glucose level occurring
from five to six hours after injection (Lozoya-Meckes and
Mellado-Campos 1985, Meckes-Lozoya and Ibanez-Camacho 1985). Further investigations determined that the initial hypotension and hyperglycemia could be abolished by
administration of antihistamines or by filtration of the extract with a 0.5 pm pore-size membrane capable of retaining high molecular weight compounds such as proteins and
kinins, which might cause the release of histamine. The late
hypoglycemic effect remained, and thus is not secondary to
the initial hyperglycemia (Meckes-Lozoya and Lozoya
1989).
A number of other plants, including Allium cepa, A. sativa, Brassica o/eracea, Hordeum vulgare, Oplopanax horridum, Phaseo/us vulgaris, Saccharomyces cerevisiae, Urtica dioica, and Vaccinium myrtillus have been reported to
contain hyperglycemic as well as hypoglycemic constituents
(Oliver-Bever and Zahnd 1979). Caution should therefore
be employed in interpreting the results of in vivo administration of crude extracts.
S8
S9
Fig. 15. Hypoglycemic alkaloids from Tecoma.
There is extensive evidence for involvement of both cellular and humoral immune phenomena in the destruction of
pancreatic p-cells characteristic of IDDM (Spencer and
Cudworth 1983, Bottazzo 1986, Montana et al. 1989). Immunosuppressive drug therapy has been recommended in
some cases of IDDM (e.g. Vardi et al. 1986). An enzymelinked immunosorbent assay (ELISA) has been developed
as a means of quantifying humoral immune responses in
rats exposed to immunomodulating chemicals (Koller et al.
1983). This assay could be used for screening plant extracts
and isolates for immunomodulating activity.
Unquestionably, in vivo bioassays are essential to prove
the value of new hypoglycemic agents. However, whole animal tests reveal relatively little about the mechanism of action of the compound, and it can be seen from the previous
section that there are a great many mechanisms by which
blood glucose levels may be reduced. Some of these mechanisms, such as those involving hepatotoxicity, are obviously not useful in diabetes therapy. The lack of perfect models
for NIDDM and IDDM, coupled with financial restrictions
on obtaining and maintaining animals, and social restrictions on extensive use of animals in experimentation, indicate that a more practical approach would involve a series
of in vitro prescreens before testing a potential new hypoglycemic agent in animals. This is in agreement with the position statement of the American Diabetes Association
(1990) that antidiabetic research should use alternative
methods to live animals when appropriate.
In Vitro Techniques
Many in vitro techniques have been developed to elucidate the varied mechanisms of action of hypoglycemic
agents discovered by in vivo bioassays. For the purpose of
screening large numbers of plant extracts and chromatographic fractions in order to isolate novel hypoglycemic
agents, some of these in vitro bioassays should be employed
as the first steps rather than the last steps of drug discovery.
Three aspects of the hypoglycemic response are commonly studied in vitro: insulin release from the pancreatic islets,
peripheral insulin binding and glucose utilization, and effects on hepatic enzymes.
For studying the effect of potential hypoglycemic agents
on the release of insulin, perfused pancreas, intact isolated
islets, and dispersed islet cell techniques have been devel-

oped. Characteristics of insulin and glucagon release from
these preparations have been studied comparatively by
Weir et al. (1986). Most of the original work was done with
tissues from rats, for which the experimental techniques of
isolation and culture are well established (Larner and Pohl
1984a,b, 1985, Pipeleers 1986,1987, Pipeleers et al. 1991).
More appropriate to large scale screening procedures are
the techniques of Ricordi et al. (1986, 1988) for the mass
isolation of porcine and human pancreatic islets. Much of
the recent work on the mechanism of sulfonylureas at the
cellular and subcellular level has been done with cultured ~
cells (e.g., Boyd 1988, Gorus et al. 1988, Garvey 1992,
Lienhard et al. 1992).
Non-insulin-dependent diabetes mellitus is not due just
to a defect in the ~-cells, but rather to a collusion between
~-cells, the liver, and peripheral tissues (DeFronzo 1988,
1992, Mueckler 1990, Granner and O'Brien 1992). Hepatic involvement in diabetes and its therapy has been studied
in primary cultures of rat hepatocytes (e.g., Salhanick et al.
1983, Rinninger et al. 1984, McCormick et al. 1986) using
techniques developed by Fry et al. (1976) and Bellemann et
al. (1977). More recently, a human hepatoma cell line has
been used to study insulin receptors (McClain and Olefsky
1988). Hikino's group has done mechanistic studies on
plant hypoglycemic agents with a variety of hepatic enzyme
preparations (Hikino et al. 1989a,b, Suzuki and Hikino
1989).
For studying in vitro insulin resistance, insulin internalization, and glucose transport in peripheral tissues, the
most common techniques involve cultures of skeletal muscle strips or cells (Beck-Nielsen et al. 1992) or adipocytes
derived from rat epididymal pads (Jochen and Berhanu
1987) or from humans by surgical excision (Kashiwagi et
al. 1983) or less invasive needle biopsy (Yki-]iirvinen et al.
1986). The effect of natural products on glucose uptake
and metabolism in peripheral tissues has also been studied
by use of fragments or a homogenate of the rat's small intestine (Hikino et al. 1989a,b). These methods could also
be adapted to use larger animal tissues available from
slaughterhouses.
Screening techniques have been developed to detect in vitro natural products that show immunoreactivity with
guinea pig insulin (de Pablo et al. 1986), inhibition of long
chain farty acid oxidation (Kanamaru et al. 1985), elevation of intracellular cAMP concentration (Swanson et al.
1988), and inhibition of protein-tyrosine kinase activity
(Geahlen et al. 1989).
Finally, the measurement of insulin levels is a critical step
in several of the bioassays. The original immunoassay technique (Wright et al. 1968, 1971, Makulu et al. 1969) was
replaced by a radioimmunoassay technique that earned a
Nobel prize for its developer (Yalow 1978), and is still the
most widely used technique. However, an enzyme-linked
immunosorbent assay (ELISA) with increased sensitivity,
high accuracy, and greater practicability (Kekow et al.
155
1988) may soon replace radioimmunoassay as the method

of choice.
Toxicity of Hypoglycemic Plants
If most hypoglycemic plant constituents have arisen

through coevolution as chemical defense compounds, then
it should be recognized that for the source plant's survival,
the best strategy is a non-selective toxin which will deter
herbivory regardless of the species of herbivore attacking it.
Often the development of new drugs from plants does not
involve increasing the potency of the lead natural product
because this has been optimized by millions of years of coevolution. Rather, the task is to achieve optimum selectivity
and minimize general toxicity. Quantitative structure-activity relationship analysis is an essential tool for achieving
this goal.
While a long history of traditional medicinal use may
suggest that a plant is relatively non-toxic, this should be
confirmed by in-depth literature review and properly-controlled experimental bioassays. Some of the reports of toxicity for antidiabetic plants are derived from case studies or
Poison Control Center reports of human poisoning or injury. Species known to contain toxic constituents, such as
pyrrolizidine alkaloids, were recorded in the database for
this review as toxic, even though the actual concentration
in the plant may not be known.
Information was also included from acute toxicity studies. Usually performed by i.p. injection of extracts into rodents, they do not necessarily relate closely to human oral
toxicity (Irwin 1962). Also, the technique is not employed
with as much standardization as it should be, e.g., extracts
are prepared differently, and mortality may be recorded after 24 hours (der Marderosian et al. 1976) or 7 to 14 days
(Klaasen 1980). For this study a plant was considered toxic if the median lethal dose (LDso) by i.p. administration in
mammals was 500 mg/kg or less.
Approximately one-third (377 species) of the plants associated with the treatment of diabetes are to be considered
toxic by the above criteria, while for another third their
safety is uncertain. In some cases, such as the ingestion of
unripe akee fruit (Blighia sapida Koenig, Sapindaceae), toxicity is expressed in part as a profound hypoglycemia
caused by the constituents, hypoglycin A and B (27 and 28
in Fig. 6). There are many other toxicological effects of
plants which may result in hypoglycemia, such as hepatotoxicity or ~-adrenergic blockade. Many plants used to
treat diabetes or shown experimentally to be hypoglycemic
have toxic effects unrelated to their desired effect.
Toxicity is influenced by the plant part, method of preparation, route of administration, and test organism. For example, the leaves of Abrus precatorius L. (Fabaceae) are
used in traditional medicine to treat diabetes, and both the
leaves and roots have been used to sweeten foods. While
156
the leaves and roots are relatively non-toxic and non-mutagenic (Choi et al. 1989), the seeds contain the glycoprotein,
abrin, one of the most potent of all known botanical toxins,
with a minimum lethal dose of 0.7 pg/kg when administered i.v. to mice. Sublethal doses of abrin i.v. are hypoglycemic (Fodstad et al. 1979), but since a single well-chewed
seed can be fatal to a human (Lampe and McCann 1985),
the seed or isolated abrin are not suitable alternative hypoglycemic agents.
When calculated on the basis of dose per body weight,
humans are generally vulnerable to a drug at a dose onetenth that shown to have the same effect in experimental
animals; when calculated per unit of body surface area,
toxic effects in man are usually within the same dosage
range as animals (Klaassen 1980). With i.p. administration,
the peritoneal cavity offers a large absorbing surface from
which drugs enter the circulation rapidly. The dose-response relationship might be quite different from oral administration, where absorption from the gastrointestinal
tract is governed by a wide variety of factors, including proportion of the drug in non-ionized form, presence of food,
gastric emptying time, decomposition of the drug by gastric
acids and enzymes, diffusion rate across the gastrointestinal
epithelium, and the "first-pass effect" of gastrointestinal
epithelial and hepatic drug-metabolizing enzymes (Mayer
et al. 1980).
Since a very small dose of some toxic drugs provides important therapeutic effects, while a large dose of other
drugs with low toxicity is required to achieve the desired effect, more useful information would be provided by the
Therapeutic Index, which is generally expressed as a ratio
of the median lethal dose to the median effective dose
(LDsJEDso), or the Certain Safety Factor (LD 1IED 99 ).
However, such information is rarely available for plants
other than those already well known to modern pharmacology.
Allergenicity and photosensitization are other aspects of
toxicity that would not be revealed by regular acute toxicity tests, yet are significant risks in the therapeutic use of
plants, especially when employing members of the Anacardiaceae (urushiol), Asteraceae (thiophenes, sesquiterpene
lactones), Hypericaceae (hypericin), and Apiaceae (furanocoumarins). Lewis and Elvin-Lewis (1977) and Lampe and
McCann (1985) have tabulated many of the plants believed
to cause these problems. The mutagenicity of any compound with potential for therapeutic use should also be examined (Ames et al. 1975, Skopek et al. 1978a,b).In general, little is known about the chronic toxicity of plants. Since
diabetes mellitus is a chronic condition with no known
cure, antidiabetic drugs must be taken for the lifetime of the
patient. It is therefore important that chronic toxicity studies be performed before recommending a plant-derived
drug for antidiabetic therapy.
Prospects for Future Antidiabetic

Plant Research
For both the discovery of locally available alternative
medicines to treat diabetics in developing countries, and for
the commercial development of new botanical hypoglycemic agents and adjuncts to antidiabetic therapy, the best
strategy will involve the study of traditional antidiabetic
plants.
There will be a number of obstacles to overcome, not the
least of which is financial. To bring a new drug to market,
it will likely cost more than $300 million and 10 years to
perform the pharmacological and toxicological testing required by current strict regulations such as those of the u.S.
Food and Drug Administration (Soejarto and Farnsworth
1989). Only pharmaceutical companies can afford this type
of investment, and they will only undertake such projects if
they can be assured of recovering their costs and making a
profit, through patent protection. While it is possible to
patent a natural product, particular applications, and derivatives made from it, it is difficult to obtain the degree of
patent coverage for a plant isolate that would be desired by
most companies (Tyler 1979).
The cost of bringing a new plant-derived drug to market
could be reduced substantially by changes in government
regulations regarding the methods for proving efficacy and
safety of traditionally used drugs from natural sources. The
current regulations of West Germany and those under development in Canada could serve as models (Morrison
1984, Tyler 1987, Blackburn et al. 1986, 1993, Liston
1986, 1987, 1990, Canada Department of National Health
and Welfare 1992).
Despite the difficulties, the financial rewards of success in
marketing plant-derived drugs are great. In the United
States, 25 % of all prescriptions dispensed from community
pharmacies in 1980 contained active principles prepared
from higher plants. Consumers paid more than $8 billion
for these prescription natural products, which include such
essential medicines as vincristine, digitoxin, quinidine, and
L-dopa (Farnsworth et al. 1985).
The supply of medicinal plants and their active constituents can also be a problem. Of the 121 natural products
currently in pharmaceutical use, only 12 % are produced
commercially by synthesis (Farnsworth et al. 1985). While
it may be technically possible to synthesize most of these
compounds, their chemical complexity often makes it more
economical to obtain them by isolation. Collection from
the wild, cultivation, or tissue culture of medicinal plants,
are techniques that involve many more problems.
More than one-third of all plant-derived drugs come
from tropical rainforest species, and that proportion could
be expected to rise substantially if we could learn as much
about the phytochemistry and pharmacology of tropical
plants as we now know of temperate and subtropical
plants. Even with their greater accessibility and longer his-

tory of study, most temperate plants have not been exhaustively studied for therapeutic usefulness (Soejarto and
Farnsworth 1989). Thus, the destruction of tropical rainforests is resulting in the loss of a tremendous natural resource for potential new drugs, in terms of supply of the
plants themselves, their germ plasm which would be necessary for genetic improvement of cultivated varieties and tissue cultures, and their constituents which could serve as
new drugs or prototypes for synthetic drug research. Hopefully, the economic potential of novel drugs derived from
primary rainforest species could serve as an incentive for
preservation of the rainforest and its management as a renewable resource rather than just a source of land for mineral and agricultural exploitation.
The rapidity with which the rainforest is being destroyed,
and the urgent need for alternative medicines for diabetes
throughout the world, underscore the need for immediate
expansion of the current level of research on antidiabetic
medicines from plants. This is probably the motivation behind the numerous reviews on antidiabetic plants published
in the last few years.
The first step needed to accelerate antidiabetic plant research is to compile a more comprehensive review of antidiabetic plants than has previously been published, which is
being accomplished in the present work. Next, high priority plants need to be selected from the general list. The criteria for high priority may vary from one researcher to another, based on their particular interests, national and institutional health goals, and geographic location. However,
the following general criteria may be useful:
1. Traditional use in one or more countries.
2. Experimentally determined hypoglycemic activity.
3. Lack of detailed information on hypoglycemic constituents.
4. Experimental evidence for low toxicity.
5. Botanical abundance.
Thus, plants which show great promise but are already
under extensive investigation would be excluded from this
list, although they may be of great interest to clinical researchers. Hypoglycemic plants which are uncommon or
not abundant are excluded because of potential supply
problems, although they might be readily available to researchers in certain locations or might be amenable to cultivation. Past experience with relatively common, large
plants like the western yew (Taxus brevifolia Nutt., Taxaceae) as a source of the anticancer drug taxol (Wall and Wani 1994) suggests that in most cases sustainable harvest of
medicinal plants from the wild is not feasible for commercial drug production, so the environmental impact of harvest and agronomics (including farm and tissue culture production) of plants being considered for development must
be studied.
The best strategy for screening the high priority plant extracts and chromatographic fractions for antidiabetic activity would be to select one or two in vitro bioassays, e.g., a
157
pancreatic islet culture for stimulation of insulin release

and an adipocyte culture for insulin binding and peripheral
glucose transport and metabolism. Active isolates could
then be subjected to in vitro screens for general toxicity,
such as the brine shrimp bioassay (Meyer et al. 1982, Alkofahi et al. 1989), mutagenicity, and hepatic enzyme effects.
Active isolates with no mutagenicity and low potential toxicity, could then be subjected to in vivo bioassays for hypoglycemic activity and toxicity. This method should allow
the discovery of more natural hypoglycemic compounds
with therapeutic potential, with less use of expensive and
highly regulated live animal research.
The final steps in the process of drug development for
antidiabetic agents from plants wiII be the pharmaceutical
preparation and distribution of the proven product. Farnsworth et al. (1985) and the World Health Organization
(1991) have outlined the steps necessary to identify, evaluate the safety and efficacy, and prepare plant-derived drugs
for therapeutic use. In many cases the use of a standardized
galenical preparation of a drug is equally efficacious and
much less expensive than using a purified active principle
prepared as a tablet or injection, and so would better suit
the needs of primary health care in developing nations. Details of plant identification, part to be used, preparation,
chemical and biological standardization of the extract,
stability of the extract, dosage regimens, therapeutic and
side effects, drug and food interactions, and contraindications, could be incorporated into the national pharmacopoeia or a supplementary herbal formulary. A good example of this type of drug development is provided by Hansson et al. (1986), who described the steps taken to bring a
proven anthelmintic preparation of Ficus glabrata (Moraceae) latex from the folklore stage to routine professional
use in local government health clinics in the Amazonian
lowlands of Peru.
Since most traditional uses of plants involve consumption
of an aqueous extract, it may be practical in many cases to
prepare and distribute lyophilized extracts of standardized
composition, packaged in plasticized aluminum foil envelopes. This method of preparation is relatively inexpensive,
within the technological means of most countries, resistant
to decomposition by heat and humidity, easily transportable, and can provide a fixed dose, needing only to be reconstituted with boiled water. It has also been found to be
acceptable to rural people accustomed to taking traditional
herbal decoctions as medicines (X. Lozoya, personal communication). Distribution can involve both modern clinics
in rural areas and the organizations of traditional healers
which many countries are now encouraging to become involved in cooperative efforts to improve primary health
care (Bannermann 1983).
It will be essential to involve traditional healers, educated
local people, and medical professionals, working together
to derive the greatest benefit from new drugs developed
from traditional remedies. Since the major diseases in devel-
158
oping countries are largely brought about by a synergism

between malnutrition (protein and energy) and infectious
and/or parasitic diseases, the control of diabetes will have a
low national priority, so any control program proposed
must be simple and inexpensive. Some practical suggestions
for antidiabetic health care programs in developing countries are provided by Bollag (1983). Finally, this must not be
an isolated effort, but rather part of a comprehensive public
health program for the development of clean water and
good nutrition, without which provision of new medicines
will have little impact on the people's health status.
Conclusions
More than 1200 species of plants have been involved in
the therapy of diabetes mellitus, half as traditional remedies
and half as experimental agents studied for their hypoglycemic effects. More than 80 % of those traditional remedies
studied pharmacologically were demonstrated to have hypoglycemic activity, indicating the value of studying traditional remedies as a source for new hypoglycemic agents.
However, further analysis revealed a great variety of mechanisms of action for their hypoglycemic effects, not all of
which are therapeutically useful. More than one-third of all
the plants described here have been reported to be toxic,
emphasizing the need for carefully planned scientific research to identify those hypoglycemic plants with true therapeutic efficacy and safety.
While different researchers will have different priorities,
this comprehensive literature review can serve as a useful
tool for the selection of plants with strong potential for the
discovery of novel antidiabetic agents, and the compilation
of a "top 20" list has been suggested. Information has also
been provided on some of the methodology which will be
necessary for the bioassay-guided isolation of potential hypoglycemic natural products and their in vitro and in vivo
pharmacological evaluation.
With the increasing incidence of diabetes mellitus in rural
populations throughout the world, the inability of current
therapies to control all the metabolic defects of the disease
and their pathological consequences, and the great expense
of modern therapy, there is a clear need for the development of alternative strategies for diabetes therapy. The
main objective of this work has been to provide some impetus to the development of such strategies. Through provision of a logical starting point and information on practical
methods, it is hoped that this work wiII lead to both the development of indigenous botanical resources as inexpensive
sources for new hypoglycemiC drugs, and the discovery of
novel hypoglycemic compounds which can serve as models
for modern hypoglycemic drug development.
Acknowledgements
The authors wish to thank Ms. Mary Lou Quinn and the staff of
the NAPRALERT project, Program for Collaborative Research in
the Pharmaceutical Sciences (PCRPS), College of Pharmacy, University of lllinois at Chicago, for their assistance in obtaining much
of the information on antidiabetic plants reported herein, and Dr.
A. Bingel of PCRPS for helpful suggestions and advice.
References
Adams, E: The Extant Works of Aretaeus, the Cappadocian. Republication of 1856 edition by Longwood Press, Boston, MA,
1978.
Aharonson, Z., Shani,]., Sulman, EG.: Hypoglycaemic effect of
the Salt Bush (Atriplex halimus) - a feeding source of the Sand
Rat (Psammomys obesus). Diabetologia 5: 379-383, 1969.
Ajgaonkar, S.S.: Herbal drugs in the treatment of diabetes. Int. Diabetes Fed. Bull. 24: 10- 19, 1979.
Al-Awadi, E, Gumaa, K.A.: Studies on the activity of individual
plants of an antidiabetic plant mixture. Acta Diabet. Lat. 24: 37
-41,1987.
Alberti, K.G.M.M.: "Tropical" diabetes - an elusive concept.
Practical Diabetes 5: 152-155, 1988.
Alberti, K.G.: Gliclazide: review of metabolic and vascular action.
Diabetes Metab. 20: 341- 348,1994.
Alkofahi, A., Rupprecht, J.K., Anderson, J.E., McLaughlin, J.L.,
Mikolajczak, K.L, Scott, B.A.: Search for new pesticides from
higher plants. In: Insecticides of Plant Origin (J.T. Arnason,
B.J.R. Philogene, P. Morand, eds.), pp. 25-43. ACS Symposium
Series 387, American Chemical Society, Washington, DC, 1989.
American Diabetes Association: Responsible use of animals in research. Diabetes Care 13 (Suppl.): 38, 1990.
American Pharmaceutical Association: Evaluation of Drug Interactions, 2nd ed. American Pharmaceutical Association, Washington, DC, 1976.
Ames, B.N., McCann, J., Yamasaki, E.: Methods for detecting carcinogens and mutagens with the salmonella/mammalian-microsome mutagenicity test. Mutat. Res. 31: 347- 364, 1975.
Ammon, H.P.T., Miiller, A.B.: Forskolin: From an ayurvedic remedy to a modern agent. Planta Med. 51: 473-477, 1985.
Arnason, T., Uck, E, Lambert, ]., Hebda, R.: Maya medicinal
plants of San Jose Succotz, Belize. ]. Ethnopharmacol. 2:
345-364, 1980.
Aslam, M., Stockley, I.H.: Interaction between curry ingredient
(Karela) and drug (Chlorpropamide). Lancet, i, 607, 1979.
Asthana, R.B., Misra, M.K.: Orally effective hypoglycemic agent
from Vinca rosea. Indian]. Biochem. Biophys. 16: 30-32, 1979.
Attvall, S., Fowelin,]., von Schenck, H., Lager, I., Smith, U.: Insulin resistance in Type I ( insulin-dependent) diabetes following
hypoglycemia - evidence for the importance of B-adrenergic
stimulation. Diabetologia 30: 691-697, 1987.
Augusti, K.T., Roy, V.C.M., Semple, M.: Effect of allyl propyl disulphide isolated from onion (Allium cepa L.) on glucose tolerance of alloxan diabetic rabbits. Experientia 30: 119-120,
1974.
Ayensu, E.S.: Medicinal Plants of West Africa. Reference Publications, Algonac, MI, 1978.
Bailey, c.J., Day, c.: Traditional plant medicines as treatments for
diabetes. Diabetes Care 12: 553-564, 1989.
Bailey, c.]., Day, c., Leatherdale, B.A.: Traditional plant remedies
for diabetes. Diabetic Med. 3: 185-186,1986.
Bailey, c.J., Day, c., Turner, S.L., Leatherdale, B.A.: Cerasee, a tra-

ditional treatment for diabetes. Studies in normal and streptozotocin diabetic mice. Diabetes Res. 2: 81-84, 1985.
Bannermann, R.H.: The role of traditional medicine in primary
health care. In: Traditional Medicine and Health Care Coverage
(R.H. Bannerman, J. Burton, w'-c. Ch'en, eds.), pp. 318-327.
World Health Organization, Geneva, 1983.
Beck-Nielsen, H., Hother-Nielsen, 0., Pedersen, 0.: Mechanism
of action of sulphonylureas with special reference to the extrapancreatic effect: An overview. Diabetic Med. 5: 613-620,
1988.
Beck-Nielsen,H., Vaag, A., Damsbo, P., Handberg, A., Nielsen,
O.H., Henriksen, J,E., Thye-Renn, P.: Insulin resistance in skeletal muscle in patients with NIDDM. Diabetes Care 15:
418-429,1992.
Bellemann, P., Gebhardt, R., Mecke, D.: An improved method for
the isolation of hepatocytes from liver slices. Selective removal
of trypan blue-dyeable cells. Anal. Biochem. 81: 408-415,
1977.
Bennett, P.H.: Diabetes in developing countries and unusual populations. In: Diabetes in Epidemiological Perspective (J.I. Mann,
K. Py6rala, A. Teuscher, eds.) pp. 43-57. Churchill Livingstone,
Edinburgh, 1983.
Benzi, G., Villa, R.F., Dossena, M., Vercesi, L., Gorini, A., Pastoris, 0.: Role of drugs in recovery of metabolic function of rat
brain following severe hypoglycemia. Neurochem. Res. 9:
979-992, 1984.
Berenbaum, M.: Coumarins and caterpillars: A case for coevolution. Evolution 37: 163-179, 1983.
Blackburn, J.L., Beliveau, J., Chandler, R.F., Hedley, M., Myers,
G.N., Pasen, L., Shantz, R.C., Willard, T.L., Zhu, D.: Report of
the Expert Advisory Committee on Herbs and Botanical Preparations. Health and Welfare Canada, 1986.
Blackburn, J.L., Chandler, R.E, Hedley, M., O'Neil, T., Pasen, L.,
Salvador, R., Shantz, R.C., Stelling, K., Willard, T.L., Zhu, D.:
Second Report of the Expert Advisory Committee on Herbs and
Botanical Preparations. Health Canada, 1993.
Bollag, U.: Practicable measures for the detection and care of diabetes mellitus in developing countries. In: Diabetes in Epidemiological Perspective (J.1. Mann, K. Py6rala, A. Teuscher, eds.),
pp. 345-355. Churchill Livingstone, Edinburgh, 1983.
Bottazzo, G.E: Death of a beta cell: homicide or suicide? Diabetic
Med. 3: 119-130,1986.
Boyd, A.E.III.: Sulfonylurea receptors, ion channels and fruit flies.
Diabetes 37: 847-850, 1988.
Bransome, E.D.Jr.: Financing the care of diabetes mellitus in the
U.S. Diabetes Care 15 (Suppl. 1): 1-5, 1992.
Briani, G., Bruttomesso, D., Bilardo, G., Giorato, c., Duner, E..
lori, E., Sgnaolin, E., Pedrini, P., Tiengo, A.: Guar-enriched pasta and guar gum in the dietary treatment of Type II diabetes.
Phytother. Res. 1: 177-179, 1987.
Brichard, S.M., Lederer, J., Henquin, J.e.: The insulin-like properties of vanadium: a curiosity or a perspective for the treatment
of diabetes? Diabet. Metab. 17: 435-440, 1991.
Broadstone, V.L., Pfeifer, M.A., Bajaj, V., Stagner, J.I., Samols, E.:
a-Adrenergic blockade improves glucose-potentiated insulin secretion in non-insulin-dependent diabetes mellitus. Diabetes 36:
932-937, 1987.
Campbell, D.B., Lavielle, R., Nathan, C.: The mode of action and
clinical pharmacology of gliclazide: a review. Diabetes Res. Clill.
Pract. 14 Suppl. 2: S21-36, 1991.
Canada Department of National Health and Welfare: Food and
Drug Regulations - Amendment (Schedule No. 705). CanadJ
Gazette Part 1126: 3908-3915, 1992.
Center for Economic Studies in Medicine: Direct and Indirect
159
Costs of Diabetes in the United States in 1987. American Diabetes Association, Alexandria, VA, 1988.
Ceriello, A., Giugliano, D., Quatraro, A., Donzella, c., Dipalo, G.,
Lefebvre, P.].: Vitamin E reduction of protein glycosylation in
diabetes. Diabetes Care 14: 68-72, 1991.
Chatterjee, K.P.: On the presence of an antidiabetic principle in
Momordica charantia. Indian J. Physio/. Pharmaco/. 7: 240,
1964.
Choi, Y.-H., Hussain, R.A., Pezzuto, J.M., Kinghorn, A.D., Morton, J.F.: Abrusides A-D, four novel sweet-tasting triterpene glycosides from the leaves of Abrus precatorius. j. Nat. Prod. 52:
1118-1127,1989.
Clayton, H.A., James, R.F., London, N.J.: Islet microencapsulation: a review. Acta Diabeto/ogica 30: 181-189,1993.
Cohen, A.J.: Critical review of the toxicology of coumarin with
special reference to interspecies differences in metabolism and
hepatotoxic response and their significance to man. Food Cosmet. Toxico/. 17: 277-289, 1979.
Colton, C.K., Avgoustiniatos, E.S.: Bioengineering in development
of the hybrid artificial pancreas. j. Biomech. Eng. 113:
152-170, 1991.
Cook, D.L., Ikeuchi, M.: Tolbutamide as mimic of glucose on Bcell electrical activity. ATP-sensitive K+ channels as common
pathway for both stimuli. Diabetes 38: 416- 421, 1989.
Cook, D.L., Satin, L.S., Ashford, M.L.J., Hales, e.N.: ATP-sensitive K+ channels in pancreatic ~-cells. Spare-channel hypothesis.
Diabetes 37: 495-498, 1988.
Damge, e., Michel, e., Aprahamian, M., Couvreur, P.: New approach for oral administration of insulin with polyalkylcyanoacrylate nanocapsules as drug carrier. Diabetes 37: 246-251,
1988.
Day, c., Bailey, c.J.: Hypoglycaemic agents from traditional plant
treatments for diabetes. Int. Industrial Biotech. 8: 5-8, 1988.
De, A.U., Saha, B.P.: Indolizines II. Search for potential oral hypoglycemic agents. j. Pharm. Sci. 64: 249-252, 1975.
DeFronzo, R.A.: The triumvirate: ~-cell, muscle, liver. A collusion
responsible for NIDDM. Diabetes 37: 667-687, 1988.
DeFronzo, R.A., Bonadonna, R.C., Ferrannini, E.: Pathogenesis of
NIDDM. A balanced overview. Diabetes Care 15: 318-368,
1992.
De Pablo, E, Lesniak, M.A., Hernandez, E.R., LeRoith, D., Shiloach, J., Roth, ].: Extracts of protozoa contain materials that
react specifically in the immunoassay for guinea pig insulin.
Horm. Metab. Res. 18: 82-87, 1986.
Der Marderosian, A.H., Giller, F.B., Roia, Ee.Jr.: Phytochemical
and toxicological screening of household ornamental plants potentially toxic to humans. j. Toxico/. Envir. Health 1: 939-953,
1976.
Downum, K.R.: Photoactivated biocides from higher plants. In:
ACS Symposium Series 296: Natural Resistance of Plants to
Pests: Roles of Allelochemicals (M.B. Green, P.A. Hedin, eds.),
pp. 197-205. American Chemical Society, 1986.
Ehrlich, P.R., Raven, P.H.: Butterflies and plants: A study in coevolution. Evolution 18: 586-608, 1964.
Fantus, I.G., Chayoth, R., O'Dea, L., Mariiss, E.B., Yale, J.E,
Grose, M.: Insulin binding and transport in adipocytes in neonatal streptozocin-injected rat model of diabetes melitus. Diabetes
36: 654-660, 1987.
Farnsworth, N.R.: The pharmacognosy of the periwinkles: Vinca
and Catharanthus. Lloydia 24: 105-138,1961.
Farnsworth, N.R., Akerele, 0., Bingel, A.S., Soejarto, D.D., Guo,
Z.: Medicinal plants in therapy. 81/11. World Health Org. 63:
965-981, 1985.
160
Farnsworth, N.R., Segelman, A.B.: Hypoglycemic plants. Tile and

Til/57: 41-56, 1971.
Faulds, D., Goa, K.L., Benfield, P.: Cyclosporin. A review of its
pharmacodynamic and pharmacokinetic properties, and therapeutic use in immunoregulatory disorders. Drugs 45:
953-1040, 1993.
Feng, P.e., Patrick, S.].: Studies of the action of hypoglycin-A, an
hypoglycaemic substance. Brit. j. Pharmacol. 13: 125-130,
1958.
Ferner, R.E.: Oral hypoglycemic agents. Med. Clin. N. Amer. 72:
1323-1335,1988.
Flatt, P.R., juntti-Berggren, L., Berggren, P.-O., Gould, B.].,
Swanston-Flatt, S.K.: Failure of glucose tolerance factor-containing brewer's yeast to ameliorate spontaneous diabetes in
C57BUKsj DBIDB mice. Diabetes Res. 10: 147-151, 1989.
Fodstad, 0., johannessen, j.V., Schjerven, L., Pihl, A.: Toxicity of
abrin and ricin in mice and dogs. J. Toxicol. Envir. Health 5:
1073-1084, 1979.
Forestieri, A.M., Galati, E.M., Trovato, A., Tumino, G.: Effects of
guar and carob gums on glucose, insulin and cholesterol plasma
levels in the rat. Phytother. Res. 3: 1-4, 1989.
Fry, j.R., jones, e.A., Wiebkin, P., Bellemann, P., Bridges, ].w.:
The enzymic isolation of adult rat hepatocytes in a functional
and viable state. Anal. Biochem. 71: 341-350, 1976.
Garda-Sainz, j.A., Mendlovic, E, Martinez-Olmedo, M.A.: Effects
of phorbol esters on IXJ-adrenergic-mediated and glucagon-mediated actions in isolated rat hepatocytes. Biochem. j. 228: 277280,1985.
Garvey, W.T.: Glucose transport and NIDDM. Diabetes Care 15:
396-417,1992.
Geahlen, R.L., Koonchanok, N.M., McLaughlin, j.L., Pratt, D.E.:
Inhibition of protein-tyrosine kinase activity by flavanoids and
related compounds. j. Nat. Prod. 52: 982- 986, 1989.
Gearien, j.E., Mede, K.A.: Cholinergics, anticholinesterases, and
antispasmodics. In: Principles of Medicinal Chemistry, 2nd ed.
(W.O. Foye, ed.), pp. 353-376. Lea and Febiger, Philadelphia,
1981.
Ghosal, S., Srivastava, R.S., Chatterjee, D.e., Dutta, S.K.: Fenugreekine, a new steroidal sapogenin-peptide ester of Trigonella
foenum-graecum. Phytochemistry 13: 2247- 2251, 1974.
Gill, G.V.: Problems of diabetic care in tropical countries. Practical
Diabetes 5: 156-158, 1988.
Gizurarson, S., Bechgaard, E.: Intranasal administration of insulin
to humans. Diabetes Res. Clin. Pract. 12: 71-84, 1991.
Gohdes, D.M.: Diabetes in American Indians: A growing problem.
Diabetes Care 9,609- 613, 1986.
Gorus, EK., Schuit, Ee., In't Veld, P.A., Gepts, w., Pipe leers, D.G.:
Interaction of sulfonylureas with pancreatic B-cells. A study
with glyburide. Diabetes 37: 1090- 1095, 1988.
Granner, D.K., O'Brien, R.M.: Molecular physiology and genetics
of NIDDM. Importance of metabolic staging. Diabetes Care 15:
369-395,1992.
Gupta, M.P., Arias, T.D., Correa, M., Lamba, S.S.: Ethnopharmacognostic observations on Panamanian medicinal plants. Part I.
Quart. j. Crude Drug Res. 17: 115-130, 1979.
Halberstein, R.A., Saunders, A.B.: Traditional medical practices
and medicinal plant usage on a Bahamian island. CuI. Med. Psychiat. 2: 177-179, 1978.
Hammouda, Y., Amer, M.S.: Antidiabetic effect of tecomine and
tecostanine. j. Pharm. Sci. 55: 1452-1454, 1966.
Hammouda, Y., Rashid, A.-K., Amer, M.S.: Hypoglycaemic properties of tecomine and tecostanine. Letters to the Editor. j.
Pharm. Pharmacal. 16: 833-834, 1964.
Handa, S.S., Chawla, A.S., Maninder: Hypoglycemic plants - a review. Fitoterapia 60: 195- 224, 1989.
Hanefield, M., Fischer, S., Schultze, j., Spengler, M., Wargenau,
M., Scholl berg, K., Fiicker, K.: Therapeutic potential of acarbose as first-line drug in NIDDM insufficiently treated with diet
alone. Diabetes Care 14, 732-737, 1991.
Hansson, A., Veliz, G., Naquira, e., Amren, M., Arroyo, M., Arevalo, G.: Preclinical and clinical studies with latex from Ficus
glabrata HBK, a traditional intestinal anthelmintic in the Amazonian area. J. Ethnopharmacol. 17: 105-138, 1986.
Hellerstrom, e., Andersson, A., Groth, e.G., Sandler, S., jansson,
L., Korsgren, 0., Swenne, I., Petersson, B., Tollemar, j., Tyden,
G.: Experimental pancreatic transplantation in diabetes. Diabetes Care 11 (Suppl. 1): 45-53, 1988.
Hengesh, E.j., Holcomb, G.N.: Drugs affecting sugar metabolism.
In: Principles of Medicinal Chemistry, 2nd ed., (W.O. Foye, ed.),
pp. 591-612. Lea and Febiger, Philadelphia, 1981.
Henquin, j.e., Charles, S., Nenquin, M., Mathot, E, Tamagawa,
T.: Diazoxide and D600 inhibition of insulin release. Distinct
mechanisms explain the specificity for different stimuli. Diabetes 31: 776-783, 1982.
Hii, e.S.T., Howell, S.L.: Effects of epicatichin on rat Islets of
Langerhans. Diabetes 33: 291-296, 1984.
Hikino, H., Ishiyama, M., Suzuki, Y., Konno, e.: Mechanisms of
hypoglycemic activity of ganoderan B: A glycan of Ganoderma
lucidum fruit bodies. Planta Med. 55: 423-428, 1989a.
Hikino, H., Kobayashi, M., Suzuki, Y., Konno, e.: Mechanisms of
hypoglycemic activity of aconitan A, a glycan from Aconitum
carmichaeli roots. J. Ethnopharmacol. 25: 295-304, 1989b.
Hikino, H., Konno, e., Mirin, Y., Hayashi, T.: Isolation and hypogycemic activity of ganoderans A and B, glycans of Ganoderma
lucidum fruit bodies. Planta Med. 51: 339-340, 1985a.
Hikino, H., Konno, C., Takahashi, M., Murakami, M., Kato, Y.,
Karikura, M., Hayashi, T.: Isolation and hypoglycemic activity
of dioscorans A,B,C,D,E,and F: Glycans of Dioscorea ;aponica
rhizophors. Planta Med. 52: 168-171, 1986a.
Hikino, H., Mizuno, T., Oshima, Y., Konno, C.: Isolation and hypoglycemic activity of moran A, a glycoprotein of Morus alba
root barks. Planta Med. 51: 159-160, 1985b.
Hikino, H., Murakami, M., Oshima, Y., Konno, e.: Isolation and
hypoglycemic activity of oryzarans A,B,C and D: Glycans of
Oryza sativa roots. Planta Med. 52: 490-492, 1986b.
Hikino, H., Oshima, Y., Suzuki, Y., Konno, e.: Isolation and hypoglycemic activity of panaxans F,G and H, glycans of Panax
ginseng roots. Shoyakugaku Zasshi 39: 331, 1985c.
Hikino, H., Takahashi, M., Murakami, M., Konno, e., Mirin, Y.,
Karikura, M., Hayashi, T.: Isolation and hypoglycemic activity
of arborans A and B, glycans of Aloe arborescens var. natalensis
leaves. Int. j. Crude Drug Res. 24: 183-186, 1986c.
Hikino, H., Takahashi, M., Oshima, Y., Konno, e.: Isolation and
hypoglycemic activity of oryzabrans A,B,C and D, glycans of
Oryza sativa bran. Planta Med. 54: 1-3, 1988.
Hill, R.S., Oberwetter, j.M., Boyd, A.E.III: Increase in cAMP levels
in l3-cell line potentiates insulin secretion without altering cytosolic free-calcium concentration. Diabetes 36: 440-446, 1987.
Hillebrand, I.: Pharmacological modification of digestion and absorption. Diabetic Med. 4: 147-150, 1987.
Holman, R.R., Steemson, j., Darling, P., Turner, R.e.: No glycemic benefit from guar administration in NIDDM. Diabetes Care
10: 68-71, 1987.
Hudson, j.B.: Antiviral compounds from plants. CRC Press, Boca
Raton, FL, 1990.
Ibanez-Camacho, R., Meckes-Lozoya, M., Mellado-Campos, V.:
The hypoglucemic effect of Opuntia streptacantha studied in

different animal experimental models. ]. Ethnopharmacol. 7:
175-181,1983.
Ilarde, A., Tuck, M.: Treatment of non-insulin-dependent diabetes
mellitus and its complications. A state of the art review. Drugs
and Aging 4: 470-491,1994.
Irwin, S.: Drug screening and evaluative procedures. Science 136:
123-129, 1962.
Ishizuka, T., Cooper, D.R., Arnold, T., Hernandez, H., Farese,
R.V.: Downregulation of protein kinase C and insulin-stimulated 2-deoxyglucose uptake in rat adipocytes by phorbol esters,
glucose and insulin. Diabetes 40: 1274-1281, 1991.
Ivorra, M.D., Paya, M., Villar, A.: A review of natural products
and plants as potential antidiabetic drugs. ]. Ethnopharmacol.
27: 243-275, 1989.
Jain, S.R., Sharma, S.N.: Hypoglycaemic drugs of Indian indigenous origin. Planta Med. 15: 439-442, 1967.
Jochen, A.L., Berhanu, P.: Insulin-stimulated glucose transport and
insulin internalization share a common postbinding step in adipocytes. Diabetes 36: 542-545, 1987.
Kakizaki, K., Basadonna, G., Merrell, R.C.: Allotransplantation of
islet endocrine aggregates. Diabetes 36: 315-319,1987.
Kanamaru, T., Shinagawa, S., Asai, M., Okazaki, H., Sugiyama,
Y., Fujita, T., Iwatsuka, H., Yoneda, M.: Emeriamine, an antidiabetic ~-aminobetaine derived from a novel fungal metabolite.
Life Sci. 37: 217-223,1985.
Karlstrom, B. Vessby, B., Asp, N.-G., Boberg, M., Lithell, H.,
Berne, c.: Effects of leguminous seeds in a mixed diet in non-insulin-dependent diabetic patients. Diabetes Res. 5: 199-205,
1987.
Karunanayake, E.H., Welihinda, J., Sirimanne, S.R . Sinnadorai,
G.: Oral hypoglycaemic activity of some medicinal plants of Sri
Lanka.]. Ethnopharmacol. 11: 223-231,1984.
Kashiwagi, A., Verso, M.A., Andrews, J., Vasquez, B., Reaven, G.,
Foley, J.E.: In vitro insulin resistance of human adipocytes isolated from subjects with noninsulin-dependent diabetes mellitus.
]. C/in. Invest. 72: 1246-1254, 1983.
Kekow, J., Ulrichs, K., Miiller-Ruchholtz, w., Gross, W.L.: Measurement of rat insulin. Enzyme-linked immunosorbent assay
with increased sensitivity, high accuracy and greater practicability than established radioimmunoassay. Diabetes 37: 321-326,
1988.
Khan, A.H., Burney, A.: A preliminary study of the hypoglycaemic properties of indigenous plants. Pak. ]. Med. Res. 2:
100-116, 1962.
Khanna, P., Jain, S.c., Panagariya, A., Dixit, V.P.: Hypoglycemic
activity of polypeptide-p from a plant source.]. Nat. Prod. 44:
648-655, 1981.
Kimura, Y., Okuda, H., Arichi, S.: Effects of the extract of Ganoderma lucidum on blood glucose level in rats. Planta Med. 54:
290-293, 1988.
Kinghorn, A.D.: Carcinogenic and cocarcinogenic toxins from
plants. In: Handbook of Natural Toxins. Volume 1: Plant and
Fungal Toxins (R.E Keeler, A.T. Tu, eds.), pp. 239-298. Marcel
Dekker, Inc., New York, 1983.
Klaassen, C.D.: Principles of toxicology. In: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 6th ed. (A.G.
Gilman, L.S. Goodman, A. Gilman, eds.). pp. 1602-1614. MacMillan Publishing Co., Inc., New York, 1980.
Kocialski, A.B., Marozzi, F.J.Jr., Malone, M.H.: Effects of certain
nonsteroid anti-inflammatory drugs, tolbutamide. and tetrahydroalstonine on blood glucose and carrageenin-induced pedal
edema in rats.]. Pharm. Sci. 61: 1202-1205, 1972.
Kolaczynski, J. W., Caro, J.F.: Insulin-like growth factor-l therapy
in diabetes: physiologic basis, clinical benefits. and risks. Ann.
161
Intern. Med. 120: 47-55, 1994.

Koller, L.D., Exon, J.H., Moore, S.A., Watanabe, P.G.: Evaluation
of ELISA for detecting in vivo chemical immunomodulation. ].
Toxicol. Envir. Health 11: 15-22,1983.
Konno, c., Mizuno, T., Hikino, H.: Isolation and hypoglycemic
activity of lithospermans A, Band C, glycans of Lithospermun
erythrorhizon roots. Planta Med. 51: 157-158, 1985a.
Konno, c., Mizuno, T., Hikino, H.: Isolation and hypoglycemic
activity of ephedrans A, B, C, D and E, glycans of Ephedra distachya herbs. Planta Med. 51: 162-163, 1985b.
Konno, c., Murakami, M., Oshima, Y., Hikino, H.: Isolation and
hypoglycemic activity of panaxans Q, R, S, T, and U, glycans of
Panax ginseng roots. J. Ethnopharmacol. 14: 69-74, 1985c.
Konno, c., Murayama, M., Sugiyama, K., Arai, M., Murakami,
M., Takahashi, M., Hikino, H.: Isolation and hypoglycemic activity of aconitans A, B, C and D, glycans of Aconitum carmichaeli roots. Planta Med. 51: 160-161, 1985d.
Konno, c., Suzuki, Y., Oishi, K., Munakata, E., Hikino, H.: Isolation and hypoglycemic activity of atractans A, Band C, glycans
of Atractylodes japonica rhizomes. Planta Med. 51: 102-103,
1985e.
Lampe, K.F., McCann, M.A.: AMA Handbook of Poisonous and
Injurious Plants. American Medical Association, Chicago,
1985.
Lamer, J.: Insulin and oral hypoglycemic drugs; glucagon. In:
Goodman and Gilman's The Pharmacological Basis of Therapeutics, 6th ed. (A.G. Gilman, L.S. Goodman, A. Gilman, eds.).
pp. 1497-1523. MacMillan Publishing Co., Inc., New York,
1980.
Lamer, J., Pohl, S.L. (eds.): Methods in Diabetes Research, Volume
1: Laboratory Methods, Part A. John Wiley and Sons, New
York,1984.
1: Laboratory Methods, Part B. John Wiley and Sons, New
York, 1984.
1: Laboratory Methods, Part C. John Wiley and Sons, New
York,1985.
Ledoux, S.P., Hall, C.R., Forbes, P.M., Parton, N.J., Wilson, G.L.:
Mechanisms of nicotinamide and thymidine protection from alloxan and streptozocin toxicity. Diabetes 37: 1015-1019, 1988.
Leeds, A.R.: Legume diets for diabetics? J. Plant Foods 3:
219-223,198l.
Le Marchand-Brustel, Y., Rochet, N., Gremeaux, T., Marot, I, Van
Obberghen, E.: Effect of an a-glycosidase inhibitor on experimentally-induced obesity in mice. Diabeto/ogia 33: 24-30,
1990.
Lenzen, S., Panten, U.: Alloxan: History and mechanism of action.
Diabetologia 31: 337- 342,1988.
Lewis, W.H., Elvin-Lewis, M.P.F.: Medical Botany: Plants Affecting Man's Health. John Wiley and Sons, New York, 1977.
Lienhard, G.E., Slot, J.W., James, D.E., Mueckler, M.M.: How
cells absorb glucose. Scientific Amer. 266: 86-91, 1992.
Liston, A.J.: Herbs and botanical preparations. Health and Welfare Canada Health Protection Branch Information Letter 704:
1-15,1986.
Liston, A.J.: Herbs and botanical preparations. Health and Welfare Canada Health Protection Branch Information Letter 726:
1-24,1987.
Liston, A.J.: Traditional herbal medicines. Health and Welfare
Canada Health Protectioll Branch Information Letter 771: 1-8,
1990.
Lomeo, F., Khokher, M.A., Dandona P.: Ethanol and its novel me-
162
R.
J. Maries and N. R. Farnsworth
tabolites inhibit insulin action on adipocytes. Diabetes 37: 912915, 1988.

Lotlikar, M.M., Rajarama Rao, M.R.: Pharmacology of a hypoglycemic principle isolated from the fruits of Momordica charantia. Indian}. Pharmacy 28: 129, 1966.
Lozoya-Meckes, M., Mellado-Campos, V.: Is the Tecoma stans infusion an antidiabetic remedy? }. Ethnopharmacol. 14: 1-9,
1985.
Ludvigsson, J.: Intervention at diagnosis of Type I Diabetes using
either antioxidants or photopheresis. Diabetes Metab. Rev. 9:
329-336, 1993.
MacRae, W.D., Chan, G.EQ., Wat, c.K., Towers, G.H.N., Lam,
J.: Examination of naturally occurring acetylenes for their ability to induce cytogenetic damage. Experientia 36: 1096-1097,
1980.
Makulu, D.R., Vichick, D., Wright, P.H., Sussman, K.E., Yu, P.-L.:
Insulin immunoassay by back-titration using alcohol precipitation of insulin-antibody complexes. Diabetes 18: 660-669,
1969.
Marles, R.J., Hudson, J.B., Graham, E.A., Soucy-Breau, c., Morand, P., Compadre, R.L., Compadre, C.M., Towers, G.H.N.,
Amason, J.T. : Structure-activity studies of photo activated antiviral and cytotoxic tricyclic thiophenes. Photochem. Photobiol.
56: 479-487,1992.
Mayer, S.E., Melmon, K.L., Gilman, A.G.: Introduction: the dynamics of drug absorption, distribution, and elimination. In:
Goodman and Gilman's The Pharmacological Basis of Therapeutics, 6th ed. (A.G. Gilman, L.S. Goodman, A. Gilman, eds.).
pp. 1-27. MacMillan Publishing Co., Inc., New York, 1980.
McClain, D.A., Olefsky, J.M.: Evidence for two independent pathways of insulin-receptor internalization in hepatocytes and hepatoma cells. Diabetes 37: 806-815, 1988.
McCormick, K., Williams, M.C., Sicoli, R., Chen, L.: Effect of tolazamide on basal ketogenesis, glycogenesis, and gluconeogenesis in liver obtained from normal and diabetic rats. Endocrinology 119: 1268-1273, 1986.
McMillan, D.E. Geevarghese, P.J.: Dietary cyanide and tropical
malnutrition diabetes. Diabetes Care 2: 202-208, 1979.
Meckes-Lozoya, M., Ibanez-Camacho, R.: Hepatic glycogenolysis
produced by intraperitoneal administration of total extract of
Tecoma stans in rats. Arch. Invest. Med. (Mex.) 16: 387-393,
1985.
Meckes-Lozoya, M., Lozoya, X.: Histaminic resopnse induced by
the intravenous administration of Tecoma stans crude extract in
the dog. Herba Hungarica 28: 117- 122, 1989.
Meir, P., Yaniv, Z.: An in vitro study on the effect of Momordica
charantia on glucose uptake and glucose metabolism in rats.
Planta Med. 51: 12, 1985.
Mertz, w,: Chromium in human nutrition: a review. J. Nutr. 123:
626-633, 1993.
Metz, S.A.: Exogenous arachidonic acid promotes insulin release
from intact or permeabilized rat islets by dual mechanisms. Putative activation of Ca 2+ mobilization and protein kinase C. Diabetes 37: 1453-1469,1988.
Meyer, B.N., Ferrigni, N.R., Putnam, J.E., Jacobsen, L.B., Nichols,
D.E., McLaughiin, J.L.: Brine shrimp: A convenient general bioassay for active plant constituents. Planta Med. 45: 31-34,
1982.
Mirsky, LA., Diengott, D., Perisutti, G.: The hypoglycemic and insulinase-inhibitory action of some plant growth regulators. Endocrinology 59: 715-718,1956.
Mishkinsky, J., Joseph, B., Sulman, EG., Goldschmied, A.: Hypoglycaemiceffectoftrigonelline. Lancet 1967: 1311-1312, 1967.
Misler, S., Gee, W.M., Gillis, K.D., Scharp, D.W., Falke, L.c.: ~le-
tabolite-regulated ATP-sensitive K+ channel in human pancreatic islet cells. Diabetes 38: 422-427, 1989.
Montana, E., Goday, A., Rosel, P., Casamitjana, R., Soler, J., Gomis, R.: Islet-cell antibodies: Markers of a more severe insulindependent diabetes mellitus? Diabetes Res. 11: 167-171, 1989.
Morrison, A.B.: Herbs and botanical preparations. Health and
Welfare Canada Health Protection Branch Information Letter
666: 1-3,1984.
Morrison, E., West, M.: A preliminary study of the effects of some
West Indian medicinal plants on blood sugar levels in the dog.
West Indian Med.}. 31: 194-197, 1982.
Morton, J.E: The balsam pear - an edible, medicinal, and toxic
plant. Econ. Bot. 21: 57, 1967.
Mossa, J.S.: A study on the crude antidiabetic drugs used in Arabian folk medicine. Int. J. Crude Drug Res. 23: 137-145, 1985.
Mueckler, M.: Family of glucose-transporter genes. Implications
for glucose homeostasis and diabetes. Diabetes 39: 6-11, 1990.
Muller-Wieland, D., Streicher, R., Siemeister, G., Krone, W.: Molecular biology of insulin resistance. Exp. Clin. Endocrinol. 101:
17-29,1993.
Nagarajan, S., Jain, H.C., Aulakh, G.S.: Indigenous plants used in
the control of diabetes. In: Cultivation and Utilization of Medicinal Plants (C.K. Atal, B.M. Kapur, eds.), pp. 584-604. Regional Research Laboratory, Council of Scientific and Industrial Research, Jammu-Tawi, India, 1982.
Ng, T.B., Wong, C.M., Li, W.w., Yeung, H.W.: Insulin-like molecules in Momordica charantia seeds. }. Ethnopharmacol. 15:
107-117,1986.
Ng, T.B., Yeung, H.W.: Hypoglycemic constituents of Panax ginseng. Gen. Pharmac. 16: 549-552, 1985.
Noble, R.L., Beer, C.T., Cutts, J.H.: Role of chance observation in
chemotherapy: Vinca rosea. Ann. N. Y. Acad. Sci. 76: 882-894,
1958.
Oakes, A.J., Morris, M.P.: The West Indian weedwoman of the
United States Virgin Islands. Bull. Hist. Med. 32: 164, 1958.
Obermaier, B., Ermel, B., Kirsch, D., Mushack, J., Rattenhuber, E.,
Biemer, E., Machicao, E, Haring, H.U.: Catecholamines and tumor promoting phorbolesters inhibit insulin receptor kinase and
induce insulin resistance in isolated human adipocytes. Diabetologia 30: 93-99, 1987.
Olaniyi, A.A.: A neutral constituent of Momordica foetida. Lloydia 38: 361, 1975.
Oliver-Bever, B.: Oral hypoglycaemic plants in West Africa.}. Ethnopharmacol. 2: 119- 127, 1980.
Oliver-Bever, B.: Medicinal Plants in Tropical West Africa. Cambridge University Press, Cambridge,1986.
Oliver-Bever, B., Zahnd, G.R.: Plants with oral hypoglycaemic action. Quart.}. Crude Drug Res. 17: 139-196,1979.
Ozden, I., Deniz, G., Tasali, E., Ulusaraty, A., Altu_, T.,
Biiyiikdevrim, S.: The effect of vitamin E on glycosylated hemoglobin levels in diabetic rats: A preliminary report. Diabetes
Res. 12: 123-124, 1989.
Paolisso, G., Sgambato, S., Pizza, G., Passariello, N., Varricchio,
M., D'Onofrio, E: Improved insulin response by chronic magnesium administration in aged NIDDM subjects. Diabetes Care
12: 265-269, 1989.
Peters, A.L., Davidson, M.B.: Insulin plus a sulfonylurea agent for
treating Type II diabetes. Ann. Intern. Med. 115: 45-53, 1991.
Pfeiffer, E.E: On the way to the automated (blood) glucose regulation in diabetes: The dark past, the grey present and the rosy future. Diabetologia 30: 51-65, 1987.
Pillay, T.S., Makgoba, M.W.: Molecular mechanisms of insulin resistance. S. Afr. Med. J. 79: 607-613, 1991.

Pipeleers, D.: Purified islet cells in diabetes research? Hormone
Res. 23: 225-234, 1986.
Pipeleers, D.: The biosociology of pancreatic ~ cells. Diabetologia
30: 277-291, 1987.
Pipeleers, D., Pipeleers-Marichal, M., Hannaert, J.C, Berghmans,
M., In't Veld, P.A., Rozing, ]., van de Winkel, M., Gepts, W.:
Transplantation of purified islet cells in diabetic rats. Diabetes
40:908-919,1991.
Pons, J.A., Stevenson, D.S.: Effect of Momordica charantia (cundeamor) in diabetes mellitus. I. A test for hypoglycemic activity
in an alcoholic extract. Puerto Rico ] . Pub. Health Trop. Med.
19: 196 (CA 38: 2117-9),1943.
Porte, D.Jr., Kahn, S.E.: Mechanisms for hyperglycemia in type II
diabetes mellitus: therapeutic implications for sulfonylurea
treatment - an update. Am. ]. Med. 90: 8S- 14S, 1991.
Portha, B., Giroix, M.-H., Serradas, P., Welsh, N., Hellerstrom, C,
Sener, A., Malaisse, W.].: Insulin production and glucose metabolism in isolated pancreatic islets of rats with NIDDM. Diabetes
37: 1226-1233, 1988.
Rahman, A.-V., Zaman, K.: Medicinal plants with hypoglycemic
activity.]. Ethnopharmacol. 26: 1-55, 1989.
Ram, S.: Karela and diabetes.]. Indian Med. Assoc. 19: 181, 1956.
Reddy, S.S.-K., Kahn, CR.: Insulin resistance: A look at the role of
insulin receptor kinase. Diabetic Med. 5: 621-629,1988.
Reuser, A.J., Wisselaar, H.A.: An evaluation of the potential side
effects of a-glucosidase inhibitors used for the management of
diabetes mellitus. Eur.]. Clin. Invest. 24 Suppl. 3: 19-24, 1994.
Rhinehart, B.L., Robinson, K.M., Payne, A.J., Wheatly, M.E.,
Fisher, ].L., Liu, P.S., Cheng, W.: Castanospermine blocks the
hyperglycemic response to carbohydrates in vivo: a result of intestinal disaccharidase inhibition. Life Sci. 41: 2325-2331,
1987.
Ricci, G.C, Ricordati, M.: Physiopathologic and clinical therapeutic effects of an alkaloid from Rauwolfia serpentina and of its
total extracts. 1. Glycemic changes caused in normo- and hypoglycemic subjects by reserpine, total extracts plus glucose, insulin and adrenaline Arch. "E. Maragliano" Patol. e Clin. 11:
359-401 (CA 50: 4401h), 1955.
Ricordi, C., Finke, E.H., Lacy, P.E.: A method for the mass isolation of islets from the adult pig pancreas. Diabetes 35: 649-653,
1986.
Ricordi, C., Lacy, P.E., Finke, E.H., Olack, B.]., Scharp, D.W.: Automated method for isolation of human pancreatic islets. Diabetes 37: 413-420,1988.
Rinninger, E, Kirsch, D., Haring, H.V., Kemmler, W.: Extrapancreatic action of the sulfonylurea gliquidone: Post-receptor effect on insulin-stimulated glycogen synthesis in rat hepatocytes
in primary culture. Diabetologia 26: 462-465, 1984.
Rivera, G.: Preliminary chemical and pharmacological studies on
"cundeamor," Momordica charantia, I. Amer. J. Pharm. 113:
281,1941.
Rivera, G.: Preliminary chemical and pharmacological studies on
"cundeamor," Momordica charantia, II. Amer.J. Pharm. 114:
72,1942.
Robertson, R.P.: Eicosanoids as pluripotential modularors of pancreatic islet function. Diabetes 37: 367-370, 1988.
Rosen, P., Herberg, L., Reinauer, H., Adrian, M., Feuerstein, J.,
Topiitt, B.: Different types of postinsulin recepror defects contribute to insulin resistance in hearts of obese Zucker rats. Endocrinology 119: 1285-1291,1986.
Rossini, A.A., Mordes, J.P., Handler, E.S.: Speculations on etiology of diabetes mellitus. Tumbler Hypothesis. Diabetes 37:
257-261,1988.
Saffran, M., Kumar, G.S., Savariar, C, Burnham, J.C, Williams,
163
F., Neckers, D.C.: A new approach to the oral administration of

insulin and other peptide drugs. Science 233: 1081-1084, 1986.
Salhanick, A.I., Konowitz, P., Amatruda, J.M.: Potentiation of insulin action by a sulfonlyurea in primary cultures of hepatocytes
from normal and diabetic rats. Diabetes 32: 206-212,1983.
Saltiel, A.R.: Second messengers of insulin action. Diabetes Care
13: 244-256, 1990.
Saltiel, A.R., Fox, J.A., Sheriine, P., Cuatrecasas, P.: Insulin-stimulated hydrolysis of a novel glycolipid generates modulators of
cAMP phosphodiesterase. Science 233: 967- 972, 1986.
Schraer, CD., Lanier, A.P., Boyko, E.J., Gohdes, D., Murphy, N.].:
Prevalence of diabetes mellitus in Alaskan Eskimos, Indians and
Aleuts. Diabetes Care 11: 693- 700, 1988.
Shani, ]., Goldschmied, A., Joseph, B., Ahronson, Z., Sulman,
F.G.: Hypoglycaemic effect of Trigonelfa foenum graecum and
Lupinus termis (Leguminosae) seeds and their major alkaloids
in alloxan-diabetic and normal rats. Arch. Int. Pharmacodyn.
210: 27- 37, 1974.
Singh, Y.N.: Traditional medicine in Fiji: some herbal folk cures
used by Fiji Indians. J. Ethnopharmacol. 15: 57-88, 1986.
Sirtori, C.R., Pasik, C: Reevaluation of a biguanide, metformin:
mechanism of action and tolerability. Pharmacol. Res. 30:
187-228,1994.
Skopek, T.R., Liber, H.L., Kaden, D.A., Thilly, w.G.: Relative sensitivities of forward and reverse mutation assays in Salmonella
typhimurium. Proc. Natl. Acad. Sci. USA 75: 4465-4469,
1978.
Skopek, T.R., Liber, H.L., Krolewski, J.J., Thilly, W.G.: Quantitative forward mutation assay in Salmonelfa typhimurium using
8-azaguanine resistance as a genetic marker. Proc. Natl. Acad.
Sci. USA 75: 410-414,1978.
Snell, K.: Non-hormonal hypoglycaemic compounds. Hypoglycaemia caused by indole and quinoline derivatives. Biochem. Soc.
Trans. 7: 745-749, 1979.
Soejarto, D.D., Farnsworth, N.R.: Tropical rain forests: Potential
source of new drugs? Perspectives in BioI. and Med. 32:
244-256,1989.
Sowell, M.O., Treutelaar, M.K., Burant, CF., Buse, M.G.: Minimal effects of phorbol esters on glucose transport and insulin
sensitivity of rat skeletal muscle. Diabetes 37: 499-506, 1988.
Spencer, K.C: Introduction: Chemistry and coevolution. In:
Chemical Mediation of Coevolution (K.C Spencer, ed.), pp.
1-11. Academic Press, San Diego, 1988.
Spencer, K.M., Cudworth, A.G.: The aetiology of insulin dependent diabetes mellitus. In: Diabetes in Epidemiological Perspective (J.I. Mann, K. Pyorala, A. Teuscher, eds.), pp. 99-121.
Churchill Livingstone, Edinburgh, 1983.
Spjut, R.W., Perdue, R.E.Jr.: Plant folklore: A tool for predicting
sources of antitumor activity? Cancer Treat. Rep. 60: 979-985,
1976.
Strong, D.R., Lawton, ].H., Southwood, R.: Insects on Plants:
Community Patterns and Mechanisms. Harvard University
Press, Cambridge, MA, 1984.
Suzuki, Y., Hikino, H.: Mechanisms of hypoglycemic activity of
panaxans A and B, glycans of Panax ginseng roots: Effects on
the key enzymes of glucose metabolism in the liver of mice. Phytother. Res. 3: 15-19, 1989a.
Suzuki, Y., Hikino, H.: Mechanisms of hypoglycemic activity of
panaxans A and B, glycans of Panax ginseng roots: Effects on
plasma level, secretion, sensitivity and binding of insulin in
mice. Phytother. Res. 3: 20-24, 1989b.
Svoboda, G.H., Gorman, M., Root, M.A.: Alkaloids of Vinca
rosea (Catharanthus roseus). XXVIII. A preliminary report on
hypoglycemic activity. Lloydia 27: 361-363, 1964.
164
Svoboda, G.H., Neuss, N., Gorman, M.: Alkaloids of Vinca rosea

Linn. (Catharanthus roseus G. Don.) V. J. Amer. Pharm. Assoc.
48: 659-667, 1959.
Swanson, S.M., Jiang, J.-X., Chang, Y.S., De Souza, N.]., Pezzuto,
J.M.: A rapid and sensitive bioassay involving cultured rat glioma cells to screen for substances capable of elevating intracellular cyclic AMP concentration. J. Nat. Prod. 51: 929-936, 1988.
Swanston-Flatt, S.K., Day, e., Bailey, c.J., Flatt, P.R.: Traditional
plant treatments for diabetes. Studies in normal and streptozotocin diabetic mice. Diabetologia 33: 462- 464, 1990.
Swanston-Flatt, S.K., Day, e., Flatt, P.R., Gould, B.J., Bailey, e.].:
Glycaemic effects of traditional European plant treatments for
diabetes. Studies in normal and streptozotocin diabetic mice.
Diabetes Res. 10: 69-73, 1989.
Taha, S.A.: Hypoglycemic effect of the venom from the snake Piscivorus piscivorus. Toxicologist 2:184, 1982.
Takahashi, M., Konno, e., Hikino, H.: Isolation and hypoglycemic activity of anemarans A, B, C and D, glycans of Anemarrhena asphodeloides rhizomes. Planta Med. 51: 100- 102, 1985a.
Takahashi, M., Konno, e., Hikino, H.: Isolation and hypoglycemic activity of saccharins A, B, C, D, E and F, glycans of
Saccharum officinarum stalks. Planta Med. 51: 258- 260,
1985b.
Takahashi, M., Konno, c., Hikino, H.: Isolation and hypoglycemic activity of coixans A, B, and C, glycans of Coix lachrymajobi var. ma-yuen seeds. Planta Med. 52: 64-65, 1986.
Tanaka, K., Isselbacher, K.J., Shih, V.: Isovaleric and a-methylbutyric acidemias induced by hypoglycin A: mechanism of Jamaican vomiting sickness. Science 175: 69-71, 1972.
Thorne, R.E: Phytochemistry and angiosperm phylogeny. A summary statement. In: Phytochemistry and Angiosperm Phylogeny
(D.A. Young, D.S. Seigler, eds.), pp. 233-295. Praeger Scientific, New York, 1981.
Tobin, R.B., Friend, B., Berdanier, e.D., Mehlman, M.A., De Vore,
V.: Metabolic responses of rats to chronic theophylline ingestion. J. Toxicol. Envir. Health 2: 361- 369, 1976.
Tomoda, M., Shimizu, N., Gonda, R., Kanari, M., Yamada, H.,
Hikino, H.: Anti-complementary and hypoglycemic activities of
the glycans from the seeds of Malva verticillata. Planta Med. 56:
168-170, 1990.
Tomoda, M., Shimizu, N., Oshima, Y., Takahashi, M., Murakami.
M., Hikino, H.: Hypoglycemic activity of twenty plant mucilages and three modified products. Planta Med. 53: 8-12, 1987.
Tuveson, R.W., Berenbaum, M.R., Heininger, E.: Inactivation and
mutagenesis by phototoxins using E. coli strains differing in sensitivity to near and far UV light. J. Chem. Ecol. 12: 933-947,
1986.
Tyler, V.E.: Plight of plant-drug research in the United States today.
Econ Bot. 33: 377-383, 1979.
Tyler, V.E.: Herbal medicine in America. Planta Med. 53: 1-4.
1987.
Tyler, V.E., Brady, L.R., Robbers, J.E.: Pharmacognosy, 8th ed. Lea
and Febiger, Philadelphia, 1981.
Unger, R.H., Foster, D.W.: Diabetes Mellitus. In: Williams T~xt
book of Endocrinology, 7th ed. (J.D. Wilson, D.W. Foster, eds.l.
pp. 1018-1080. W.B. Saunders, Philadelphia, 1985.
van de Werve, G.,_Proietto, j ., Jeanrenaud, B.: Tumor-promoting
phorbol esters increase basal and inhibit insulin-stimulated lipogenesis in rat adipocytes without decreasing insulin binding. Biochem.J.225: 523-527,1985.
van de Werve, G., Proietto J., Jeanrenaud B.: Control of glycogen
phosphorylase interconversion by phorbol esters, diacylglycerols, Ca 2 and hormones in isolated rat hepatocytes. Biochem . .T.
231:511-516,1985.
Vardi, P., Benderly, A., Kanter, Y., Etzioni, A.: Immunosuppressive

drugs to prevent diabetes. Diabetes Care 9: 214-215, 1986.
von Holt, C., von Holt, M., Bohm, H.: Metabolic effects of hypogycin and methylenecyclopropaneacetic acid. Biochem. Biophys. Acta 125: 11-21, 1966.
Waki, I., Kyo, H., Yasuda, M., Kimura, M.: Effects of a hypoglycemic component of Ginseng radix on insulin biosynthesis
in normal and diabetic animals. J. Pharm. Dyn. 5: 547-554,
1982.
Wall, M.E., Wani, M.e.: Taxol: Discovery to clinic. Economic and
Medicinal Plant Research 6: 299-322, 1994.
Weiner, N.: Drugs that inhibit adrenergic nerves and block adrenergic receptors. In: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 6th ed. (A.G. Gilman, L.S. Goodman,
A. Gilman, eds.). pp. 176-210. MacMillan Publishing Co., Inc.,
New York, 1980.
Weir, G.c., Leahy,J.L., Barras, E., Braunstein, L.P.: Characteristics
of insulin and glucagon release from the perfused pancreas, intact isolated islets and dispersed islet cells. Hormone Res. 24: 62
-72,1986.
Welihinda, J., Karunanayake, E.H.: Extra-pancreatic effects of
Momordica charantia in rats. J. Ethnopharmacol. 17: 247-255,
1986.
Welihinda, j., Karunanayake, E.H., Sheriff, M.H.R., jayasinghe,
K.S.A.: Effect of Momordica charantia on the glucose tolerance
in maturity onset diabetes. J. Ethnopharmacol. 17: 277-282,
1986.
White, J.R., Campbell, R.K.: Magnesium and diabetes: a review.
Ann. Pharmacother. 27: 775-780, 1993.
Williams, D.H., Stone, M.J., Hauck, P.R., Rahman, S.K.: Why are
secondary metabolites (natural products) biosynthesized? J.
Nat. Prod. 52: 1189-1208, 1989.
Winkelman, M.: Ethnobotanical treatments of diabetes in Baja California Norte. Med. Anthro. 11: 255-268, 1989.
World Health Organization: Diabetes Mellitus: Report of a WHO
Study Group. WHO Technical Report Series 727, WHO, Geneva, 1985.
World Health Organization: Guidelines for the Assessment of Herbal Medicines. Programme on Traditional Medicines. WHO/
TRMI91.4, WHO Geneva, 1991.
Wright, P.H., Makulu, D.R., Malaisse, W.]., Roberts, N.M., Yu,
P.-L.: A method for the immunoassay of insulin. Diabetes 17:
537-546,1968.
Wright, P.H., Makulu, D.R., Vichick, D., Sussman, K.E.: Insulin
immunoassay by back-titration. Some characterisitics of the
technic and the insulin precipitant action of alcohol. Diabetes
20: 33-45, 1971.
Yalow, R.S.: Radioimmunoassay: a probe for the fine structure of
biologic systems. Science 200: 1236-1245, 1978.
Yki-Jiirvinen, H., Nikkilii, E.A., Kubo, K., Foley, J.E.: Assay of
glucose transport in human fat cells obtained by needle biopsy.
Diabetologia 29: 287-290, 1986.
Yoshikuni, Y.: Inhibition of intestinal a-glucosidase activity and
postprandial hypoglycemia by moranoline and its N-alkyl derivatives. Agric. Bioi. Chem. 52: 121-128, 1988.
Young, P., Kirkham, D.M., Murphy, G.]., Cawthorne, M.A.: Evaluation of inhibitory guanine nucleotide regulatory protein G
function in hepatocyte and liver membranes from obese Zucker
(fa/fa) rats and their lean (Fa/?) littermates. Diabetologia 34:
565- 569,1991.
Zawalich, W.S.: Modulation of insulin secretion from j3-cells by
phosphoinositide-derived second-messenger molecules. Diabetes 37: 137-141,1988.

Zawalich, W.S., Diaz, V.A., Zawalich, K.C.: Influence of cAMP
and calcium on PH] inositol efflux, inositol phosphate accumulation and insulin release from isolated rat islets. Diabetes 37:
1478-1483,1988.
Address
R.J. Maries, Department of Botany, Brandon University,
Brandon, MB R7A 6A9, Canada.
165
Appendix: Antidiabetic Plants

This appendix comprises an extensive list of algae, fungi,
and plants used ethnomedically to treat diabetes mellitus or
in some way tested for therapeutic activity against diabetes
mellitus. Since research into antidiabetic plants is ongoing
in many institutions no list can claim to be comprehensive,
but this is the most complete listing published to date. The
information is drawn mostly from the computer database
NAPRALERT, created and maintained by the Program for
Collaborative Research in the Pharmaceutical Sciences,
College of Pharmacy, University of Illinois at Chicago. This
database is accessible through the commercial database service STN, operated by the American Chemical Society. To
save space references have been omitted from this appendix
but are available through NAPRALERT. Given the abbreviated nature of the information presented, this appendix is
intended to provide only a starting point for a rational antidiabetic drug discovery project, and readers are encouraged
to obtain the original references for proper evaluation of
the results abstracted here.
The following paragraphs explain the type of information and abbreviations used in the appendix table:
SCIENTIFIC NAME: Latin binomials are given as they
appear in the references, with only simple typographic errors corrected. Since botanical authorities were sometimes
given and sometimes omitted in the original references,
they have been omitted here for consistency and saving of
space.
ETH: Ethnopharmacological use. The number refers to
the number of countries in which the plant is used traditionally to treat diabetes.
ACTIVITY: Antidiabetic activity. +: active; =: equivocal;
-: inactive; ?: conflicting reports. Pretreattnent or precondition of experimental animals: A: alloxan; B: 2,4-dinitrophenol; C: cholesterol; D: spontaneous diabetes; E: epinephrine; G: glucose; K: corticotropin; L: glucagon; N: normal; 0: ethanol; P: pancreatectomy; S: streptozotocin; T:
somatotropin; U: unspecified; X: anterior pituitary extract;
Z: diazoxide.
PART TESTED: Abbreviations: ap: aerial parts; bl: bulb;
br: bran; cm: corm; fl: flower; fr: fruit; gl: gall; gm: gum; is:
isolate; If: leaf; mu: mucilage; rb: root bark; rn: resin; rt:
root; rz: rhizome; sb: stem bark; sd: seed; sh: shoot; sp: sap;
st: stem; sy: styles; tb: tuber; wd: wood; wp: whole plant.
ROUTE ADMIN.: im: intramuscular; in: inhaled; ip: intraperitoneal; iv: intravenous; po: per os; pn: per nares; sc:
subcutaneous; vt: in vitro.
ACTIVE CONSTITUENT: Constituents present which
have been reported to have blood glucose lowering activity.
TOXICITY: toxidnontoxic: some parts toxic, other parts
nontoxic; ?: questionable toxicity.
166
FAMILY
SCIENTIFIC NAME
PROTISTA
Rhodophyta:
Corallinaceae
Gelidiaceae
Phyllophoraceae
Phaeophyta:
Laminariaceae
Laminariaceae
Cystoseiraceae
Ern
ACTIVITY
PART
TESTED
ROUTE
ADMIN.
ACTIVE
CONSTmJENT
Corallina rubens
+N
wp
iv
Pterocladia capillacea
Phyllophora nervosa
+A,N
-N
wp
wp
IV
polypeptide of
Asp, Glu, Gly,
Sec, and The
polypeptide
Laminaria ochroleuca
Saccorhiza polyschides
Cystoseira barbata
-N
-N
+N
wp
wp
wp
po
po
Fucaceae
Himanthaliaceae
Fucus vesiculosus
Himanthalia elongata
-N
+A,N
wp
wp
po
iv
Sargassaceae
Chlorophyta:
Codiaceae
FUNGI
Basidiomycotina:
Agaricaceae
Amanitaceae
Sargassum vulgare
+N
wp
iv
Codium tomentosum
-N
wp
IV
Agaricus bisporus
Amanita phalloides
+S,-N
+N
wp
po
po
Coprinaceae
Exobasidiaceae
Polyporaceae
Polyporaceae
Polyporaceae
Coprinus comatus
Laurobasidium lauri
Fomes iaponica
Ganoderma applanatum
Ganoderma lucidum
+N
-N
+N
-S
+A,E,G,N
fr
fr
fr
fr
wp
po
po
Polyporaceae
Polyporaceae
Polyporaceae
Deuteromycotina:
Moniliaceae
Ascomycotina:
Clavicipitaceae
Clavicipitaceae
Saccharomycetaceae
Pachyma hoelen
Polyporus umbellatus
Poria cocos
1
2
?Y
?A
?S,G
fr
fr
fr
po
po
po
Beauveria bassiana
?A
wp
po
Claviceps purpurea
Cordyceps cicadae
Saccharomyces cerevisiae
+N
+N
+N
sc
wp
wp
po
ip
po
Trichocomaceae
Trichocomaceae
Aspergillus niger
Emericella quadrilineata
+A,N
+D,S,N
wp
fr
po,ip
po
Lycopodium annotinum
Lycopodium clavatum
Selaginella denticulata
+N
+N
PLANTAE
Lycopodiophyta:
Lycopodiaceae
Lycopodiaceae
Selaginellaceae
Polypodiophyta:
Actiniopteridaceae
Angiopteridaceae
Cyatheaceae
Cyatheaceae
Actiniopteris australis
Angiopteris erecta
Cyathea gigantea
Cyathea nilgirensis
IV
IV
iv
IV
wp
ap
ap
ap
polypeptide of
Thr, Sec, Glu,
Pro, His, Val,
Met, ammonia
nontoxic
toxic?
polysaccharide,
protein
(unidentified)
polypeptide
phalloidin,
phallacin,
phallacidin indolic
sulfur-cont.
cyclopeptides
nontoxic
toxic
po
ip
1
-N
-N
-N
-N
TOXICITY
po
po
po
po
glycans
ganoderan
AandB
nontoxic
ergot alkaloids
toxic
vitamin B
complex. Cc,
asparrateadenosine mix
nontoxic
emericedin &
emeriamine
(B-aminobetain)
annotinine (H, iv) nontoxic?

lycopodine (H, iv) nontoxic
toxic?
nontoxic
nontoxic
nontoxic
toxic

FAMILY
SCIENTIFIC NAME
ETH
ACI1VITY
Dicksoniaceae
Osmundaceae
Polypodiaceae
Polypodiaceae
Polypodiaceae
Polypodiaceae
Polypodiaceae
Polypodiaceae
Polypodiaceae
Polypodiaceae
Polypodiaceae
Polypodiaceae
Polypodiaceae
Polypodiaceae
Polypodiaceae
Polypodiaceae
Polypodiaceae
Equisetophyta:
Equisetaceae
Equisetaceae
Equisetaceae
Equisetaceae
Gnetophyta:
Ephedraceae
Cibotium barometz
Osmunda regalis
Acrostichum aureum
Adiantum capillus-veneris
Adiantum caudatum
Athyrium dialatatum
Athyrium fimbriatum
Blechnum occidentale
Cheilanthes pruinata
Cyclophorus parasiticus
Lindsaea trapeziformia
Notholaena aurea
Polystichum setiferum
Pteris mertensioides
Tectaria cicutaria
Thelypteris mettilineata
Woodwardia radicans
-S
-N
-N
+N
?N
-N
-N
-N
167
PART
TESTED
ROUTE
ADMIN.
rz
ap
wp
wp
wp
wp
wp
wp
po
po
po
po
po
po
po
po
-N
ap
po
-N
-N
-N
-N
-N
ap
ap
ap
ap
ap
po
po
po
po
po
nontoxic
nontoxic
toxic
nontoxic
nontoxic
-N
wp
po
-N
wp
po
toxic
toxic
nontoxic
toxic
Ephedra distachya
+A,N,-S
wp
ip,po
Callitris robusta
Cupressus funebris
Juniperus communis
Juniperus phoenicea
Thu;opsis dolabrata
Abies pindrow
Pinus longifolia
Pinus roxburghii
Pinus strobus
Taxus chinensis
Taxus cuspidata
-N
-N
+S
ap
ap
fr
po
po
po
Equisetum arvense
Equisetum bogotense
Equisetum debile
Equisetum giganteum
Pinophyta
Cupressaceae
Cupressaceae
Cupressaceae
Cupressaceae
Cupressaceae
Pinaceae
Pinaceae
Pinaceae
Pinaceae
Taxaceae
Taxaceae
Magnoliophyta:
Liliopsida:
Alismataceae
Alismataceae
Amaryllidaceae
Amaryllidaceae
Alisma orientale
Alisma plantago-aquatica
Crinum defixum
Lycoris squamigera
Amaryllidaceae
Narcissus tazetta
Araceae
Araceae
Araceae
Acorus calamus
Alocasia indica
Amorphophalus kon;ac
Araceae
Araceae
Araceae
Araceae
Araceae
Araceae
Arecaceae
Arecaceae
Arecaceae
Arecaceae
Pinellia ternata
Pistia stratiotes
Rhaphidophora glauca
Rhaphidophora lancifolia
Scindapsus officinalis
Typhonium gigantellm
Acrocomia mexicana
Areca catechu
Borassus (label/ifer
Calamus thwaitesii
ACTIVE
CONSTITUENT
TOXICITY
toxic
nontoxic
toxic
toxic
toxic
nontoxic
nontoxic
nontoxic?
nontoxic
toxic
1
1
1
1
1
1
1
1
2
1
1
1
1
1
3
1
nontoxic
nontoxic
toxic?
+N
+N
+N
If,rt,sb
sb,rt
toxic
nontoxic
po
po
nontoxic?
toxic
+N
+A,Y,N,-S,G
-S
-N
+N
rz
rz
wp
bl
po,sc
po
po
po
+N
bl
po
-N
-N
+G
rz
rz
po
po
po
?Y
tb
po
-N
-N
+N
ap
ap
fr
po
po
po
toxic
nontoxic
nontoxic
nontoxic
+A
-S
-N
-N
fr,rt
fr
sp
ap
po
po
po
po
toxic
toxic
1
1
ephedrans a-e
toxic?
(A, H, ip) glycans
lycoris-S-glucomannan
narcissus-t-gluco
mannan
konjak mannan
(glucomannan)
(A, po)
nontoxic
nontoxic
toxic
toxic
toxid
nontoxic
toxic
nontoxic
168
FAMILY
SCIENTIFIC NAME
Ern
ACTIVITY
PART
TESTED
ROUfE
ADMIN.
Arecaceae
Arecaceae
Arecaceae
Arecaceae
Bromeliaceae
Bromeliaceae
Bromeliaceae
Cannaceae
Cannaceae
Commelinaceae
Commelinaceae
Commelinaceae
Cyperaceae
Cyperaceae
Cyperaceae
Cyperaceae
Cyperaceae
Dioscoreaceae
Dioscoreaceae
Dioscoreaceae
Cocos nucifera
Lodoicea sechellarum
Phoenix dactylifera
Serenoa serrulata
Ananas comosus
Bromelia karatas
Tillandsia usneoides
Cannaagria
Canna orientalis
Forrestia mollissima
Tradescantia multiflora
Zebrina pendula
Cyperus iria
Cyperus tegetum
Kyllinga monocephala
Ky/linga triceps
Scleria levis
Dioscorea alata
Dioscorea asclepiadea
Dioscorea batatas
1
1
1
1
1
?N
-N
fr,lf
fr
po
po
Dioscoreaceae
Dioscoreaceae
Dioscoreaceae
Dioscoreaceae
Dioscoreaceae
Dioscorea bulbifera
Dioscorea dumetorum
Dioscorea gracillima
Dioscorea hispida
Dioscorea ;aponica
Dioscoreaceae
Haemodoraceae
Hydrocharitaceae
Hypoxidaceae
Iridaceae
Iridaceae
Lemnaceae
Liliaceae
Liliaceae
Dioscorea oppositifolia
Aletris farinosa
Ottelia alismoides
Curculigo orchioides
Iris kumaonensis
Iris versicolor
Lemna polyrrhiza
Allium ascalonicum
Allium cepa
Liliaceae
Allium sativum
Liliaceae
Liliaceae
Liliaceae
Liliaceae
Liliaceae
Liliaceae
Liliaceae
Allium tuberosum
Aloe africana
Aloe arborescens
Aloe barbadensis
Aloe ferox
Aloe vera
Anemarrhena asphodeloides
Liliaceae
Liliaceae
Liliaceae
Liliaceae
Liliaceae
Liliaceae
Liliaceae
Liliaceae
Liliaceae
Aphanamixis polystachya
Asparagus cochinchi1lel/sis
Asparagus gonoclados
Chamaelirium luteum
C/intonia borealis
Colchicum luteum
COl/vallaria ma;alis
Gloriosa superba
Heterosmilax ;aponica
ACTIVE
CONSTITUENT
TOXICITY
nontoxic
nontoxic
toxic?
nontoxic
2
1
1
1
1
1
1
+N
wp
po
-N
-N
ap
wp
po
po
-N
wp
po
-N
-N
?A
+N
+A,N,?G,S,Y
rt
po
po
po
?N
+A,N
+N
ap
tb
bl
+A,N
. rz
ip
-N
ap
po
-N
+A,N
-N
wp
wp
wp
po
po
po
-S
-N
+A,E,D,G,
P,?N
wp
bl
ap,bl
+A,E,G,?N,
-S,C,D
bl
po
po
po,sc,ip,iv allyl-propyl
disulfide, allicin
(diallyl disulfide
oxide) (A, H, po),
diphenylamine
po
allyl-propyl
disulfide, allicin
(diallyl disulfide
oxide) (A, H, po)
ip
ip
po,ip
arborans A and B
po
ip
lupeol (A, po)
po,iv,ip
po,ip
anemarans a-d
(A, H, ip) (glycans)
toxic?
toxic
nontoxic
nontoxic?
nontoxic
toxic
4
1
1
wp
rz
bl
rz
ip,po
po
ip
toxic
dioscorans a-f
nontoxic
(A, H, ip) g1ycans
nontoxic
dioscoretine
nontoxic?
dioscorans a-f
(A, H, ip) glycans
5
3
-A
If
If
+N
+A,N
If
+A
sp
+N
If
+N,S,D,?A
If
+A,N,Y,?G,-S rz
-N
1
1
1
-5
-N
?N,-S
-N
st
rt
cm
If
wp
nontoxic
toxic
toxic
nontoxic
toxic
toxic
nontoxic
nontoxic
nontoxic
nontoxic
toxic
nontoxic
?
po
po
po
po
toxic
toxic
toxic

FAMILY
SCIENTIFIC NAME
Liliaceae
ETH
169
ACTIVITY
PART
TESTED
ROUTE
ADMIN.
ACTIVE
CONSTITUENT
TOXICITY
Ulium auratum
+N
bl
po
toxic
Liliaceae
Ulium speciosum
+N
bl
po
Iilium-A-glucomannan
lilium-S-glucomannan
Liliaceae
Liliaceae
Liliaceae
Liliaceae
Liliaceae
Liliaceae
Liliaceae
Liliaceae
Liliaceae
Liliaceae
Liliaceae
Liliaceae
Liliaceae
Liliaceae
Liliaceae
Musaceae
Musaceae
Musaceae
Orchidaceae
Orchidaceae
Orchidaceae
Orchidaceae
Orchidaceae
Pandanaceae
Pandanaceae
Uriope graminifolia
Ophiopogon japonicus
Polygonatum humile
Polygonatum in{latum
Polygonatum macropodum
Polygonatum multi{lorum
Polygonatum odoratum
Polygonatum officinale
Scilla sibiriea
Smilax canariensis
Trillium pendulum
Urginea indiea
Veratrum album
Veratrum ealifornicum
Veratrum viride
Ensete super bum
Musa paradisiaea
Musa sapientum
Cypripedium aeaule
Cypripedium ealceolus
Orchis latifolia
Orchis mascula
Vanda testacea
Pandanus amaryllifolius
Pandanus fureatus
tb
po
po
Pandanaceae
Pandanaceae
Poaceae
Poaceae
Poaceae
Poaceae
Poaceae
Poaceae
Poaceae
Poaceae
Poaceae
Poaceae
Poaceae
Pandanus odoratissimus
Pandanus odorus
Arundo donax
Avena fatua
Avena sativa
Bambusa arundinacea
Bambusa dendrocalamus
Bambusa nutans
Bambusa vulgaris
Bothriochloa pertusa
Chrysopogon aciculatus
Cinna arundinacea
Coix lachryma-jobi
Poaceae
Poaceae
Poaceae
Poaceae
Poaceae
Poaceae
Poaceae
Poaceae
Poaceae
Poaceae
Cymbopogon citratus
Cymbopogon {lexuosus
Cymbopogon martini
Cynodon dactylon
Dermostachys bipinnata
Eragrostis bipinnata
Eragrostis pilosa
Hordeum vulgare
Imperata cylindrica
Oryza sativa
Poaceae
Poaceae
Poaceae
Poaceae
Panicum miliaceum
Pennisetllm purpllrellm
Phragmites commllnis
Phragmites maxima
1
1
1
1
1
1
+N
+S,?A
+N
+N
+N
+G
+G,N
-N,S
+N
nontoxic?
convallamarin
rt
rt
rz
po
po
po
bl
po
1
1
1
1
1
1
1
1
1
1
1
+N
+N
+E,N
+E,N
+N
+C
+N
sd
fr
fl
po
po
-N
rt
po
-N
+G
-N
wp
rt
ap,fr
po
po
po
+A
-N
-N
-N
-D,+N,G
+A.N
+A,N
+N
+N
-N
-N
rt
If
ap
wp
sd
wp
If
ap
If
wp
wp
po
po
po
po
po
po
po,ip
po
po
po
po
+A,?N
ap,sd
po,ip
-N
-N
-N
rt
wp
wp
po
po
po
+U,N
wp
nontoxic
alkaloids
alkaloids
toxic
nontoxic?
nontoxic?
nontoxic
nontoxic?
nontoxic?
toxic
nontoxic?
toxic?
toxic
toxic
toxic
nontoxic
nontoxic
nontoxic
nontoxic
nontoxic
toxicl
nontoxic
toxic
toxic
nontoxic
nontoxic
nontoxic?
nontoxic?
nontoxic
nontoxic
nontoxic
1
1
1
1
+N
-S
rz
+A,N,?Y,-S;-G br,sd,rt
+N
-N
+A
-N
wp
ap
rz
ap
coixans a, b,
c: (H); a (A) (ip)
nontoxic
nontoxic
nontoxic
toxic
?
nontoxic?
nontoxic?
nontoxic
po
po,ip
po
po
ip
po
peptidoglycans
nontoxic
oryzarans a, b, c, d;
oryzabrans a. b, c, d
toxic
nontoxic
toxic
170
R.]. Maries and N. R. Farnsworth
FAMILY
SCIENTIFIC NAME
Ern
ACTIVITY
Poaceae
Phyllostachys bambusoides
+N
Poaceae
Poaceae
Poa pratensis
Saccharum officinarum
+N
+A,N
Poaceae
Poaceae
Poaceae
Poaceae
Poaceae
Poaceae
Setaria italica
Sporobolus indicus
Tripsacum laxum
Triticum aestivum
Triticum spelta
Zea mays
Pontederiaceae
Potamogetonaceae
Typhaceae
Zingiberaceae
Zingiberaceae
Zingiberaceae
Zingiberaceae
Zingiberaceae
Zingiberaceae
Zingiberaceae
Zingiberaceae
Zingiberaceae
Zingiberaceae
Magnoliopsida:
Acanthaceae
Acanthaceae
Acanthaceae
Acanthaceae
Acanthaceae
Acanthaceae
Acanthaceae
Acanthaceae
Acanthaceae
Acanthaceae
Acanthaceae
Acanthaceae
Acanthaceae
Acanthaceae
Acanthaceae
Acanthaceae
Aceraceae
Aizoaceae
Alangiaceae
Amaranthaceae
Amaranthaceae
Amaranthaceae
Amaranthaceae
Amaranthaceae
Amaranthaceae
Amaranthaceae
Anacardiaceae
Anacardiaceae
Monocharia hastata
Potamogeton crispus
Typha latifolia
Alpinia galanga
Alpinia khulan;an
Amomum aromaticum
Amomum subulatum
Costus schlechteri
Curcuma longa
Hedychium spicatum
Zingiber capitatum
Zingiber officinale
Zingiber zerumbet
Adhatoda vasica
Andrographis paniculata
Asteracantha longifolia
Barleria cristata
Barleria nocti{lora
Barleria prionotis
Carvia callosa
Dicliptera roxburghiana
Dipteracanthus prostratus
Hygrophila auriculata
Jacobinia suberecta
Nilgirianthus barbatus
Ruellia tuberosa
Strobilanthes boerhaavioides
Strobilanthes crispus
Thunbergia mysorensis
Acer glabrum
Glinus lotoides
Alangium salviifolium
Achyranthes aspera
Aerva lanata
Aerva sanguinolenta
Cyathula capitata
Gomphrena celosioides
Gomphrena globosa
Pfaffia paniculata
Anacardium humile
Anacardium occidentale
Anacardiaceae
Anacardiaceae
Anacardiaceae
Anacardiaceae
Anacardiaceae
Holigarna grahamii
Holigarna nigra
Mangifera indica
Pistacia lentiscus
Poupartia birrea
ROUTE
ADMIN.
ACTIVE
CONSTITUENT
TOXICITY
po
lupeol (A, po),

5-hydroxytryptamine (H, ip)
toxic?
wp
st
sc
ip
nontoxic
saccharans a, b, c, nontoxic
d, e, f: (H); c (A) (ip)
-5
-N
-N
+N,-G,S
sd
wp
ap
If,sd
po
po
po
pO,sc
+U,?N
sy
po
-N
+N
-S
-N
wp
wp
pI
rz
po
po
po
+N
+N
+D
-N
+N
-N
+D,N,?Y
rz
rz
wp
rz
rz
wp
ap,rz
po
po
po
po
po
po
po
+N
-A,N
+N
+N
-N
+N
-N
-N
+N
+G
+F
-N
If,rt
If,st
wp
wp
wp
wp
ap
wp
po
po
po
po
po
ap
po
po
po
N
?N
-N
ap
If
ap
po
po
po
-N
+N
+A,N,-S
wp
If
wp
po
po
po
-N
+U
-N
wp
wp
po
po
1
9
+A,?N,-5
If,sb,sd
po,iv
ap
ap
-N
-N
-N
If
po
po
po
+A,G,-D,N
If
po
1
1
3
PART
TESTED
toxic
toxic
nontoxic
coumarm
(A, H, po)
nontoxic
nontoxic
1
2
toxic
nontoxic
toxic?
nontoxic
nontoxic
toxic
nontoxic
nontoxic
1
2
wp
IS
lupeol
po
po
nontoxic
nontoxic
nontoxic
nontoxic
nontoxic
toxic
nontoxic
moranoline
nontoxic
nontoxic
nontoxic?
nontoxic
toxic
toxic
nontoxic
nontoxic
?
toxic
cyasterone (A, po) nontoxic?
toxic
toxic?
(-)epicatechin
(A,ip)
toxic
toxic
toxic
toxic
nontoxic
nontoxic

FAMILY
SCIENTIFIC NAME
ETH
Anacardiaceae
Anacardiaceae
Anacardiaceae
Anacardiaceae
Anacardiaceae
Anacardiaceae
Anacardiaceae
Anacardiaceae
Anacardiaceae
Annonaceae
Annonaceae
Annonaceae
Annonaceae
Apiaceae
Rhus aromatica
Rhus chinensis
Rhus coriaria
Rhus glabra
Rhus toxicodendron
Rhus typhina
Rhus wallichii
Semecarpus anacardium
Spondias dulcis
Annona squamosa
Guatteria caribea
Uvaria narum
Uvariopsis guineensis
Ammi visnaga
2
1
Apiaceae
Apiaceae
Apiaceae
Apiaceae
Apiaceae
Apiaceae
Apiaceae
Apiaceae
Apiaceae
Apiaceae
Apiaceae
Apiaceae
Anethum graveolens
Angelica gigas
Angelica shikokiana
Angelica sinensis
Apium graveolens
Arracacia brandegei
Bupleurum falcatum
Centella asiatica
Changium smyrnioides
Coriandrum sativllm
Cuminum nigrum
Daucus carota
Apiaceae
Apiaceae
Apiaceae
Apiaceae
Apiaceae
Apiaceae
Apiaceae
Apiaceae
Apocynaceae
Apocynaceae
Apocynaceae
Apocynaceae
Eryngium creticum
Eryngium foetidum
Ferula assafoetida
Hydrocotyle podantha
Myrrhis odorata
Petroselinum crispum
Peucedanum dana
Sanicula marilandica
Allamanda cathartica
Alstonia macrophylla
Alstonia scholaris
Alstonia spatulata
Apocynaceae
Apocynaceae
Apocynaceae
Apocynum androsaemifolium 1
1
Catharanthus plIsillus
Catharanthus roseus
10
Apocynaceae
Apocynaceae
Apocynaceae
Apocynaceae
Apocynaceae
Apocynaceae
Holarrhena antidysellterica
Hunteria umbellata
Plumeria rubra
Rauvolfia serpelltina
Rhazya stricta
Vinca erecta
Apocynaceae
Vinca major
ACTIVITY
PART
TESTED
+N
+N
ROUTE
ADMIN.
ACTIVE
CONSlTIUENT
1
1
1
1
1
1
1
2
1
3
1
1
1
+N
+P,N
-N
+N
+N
+N
po
ap
fr
fr
If
po,ip
po
po
po
-N
+N
+C
ap
rt
+N
-N
fr
rt
po
po
-S
-A,=E,+N
rt
If
po
sc
+N,Y
-N
?A
-A,+U,S,?N
+A,N
-D,A.S,?N
rt
wp
rt
sd
sd
rt,wp
po
po
po
po
po
po,sc
-S,N
-N
+S,N
+N
-N
gm
wp
gm
ap
ap
po
po
po
po
po
-N
+N
+N
+N
ap
wp
wp
sb
po
po
po
po
TOXICITY
toxic?
toxic?
toxic?
toxic?
toxic
toxic?
toxic
nontoxic?
nontoxic
dihydrosamidin
(A, po)
nontoxic
nontoxic
toxic
nontoxic
nontoxic
diphenylamine?
nontoxic
toxic
toxic
diphenylamine
nontoxic
nontoxic?
toxid
nontoxic
nontoxic?
nontoxic
?
nontoxic
nontoxic
toxic
171
po
+U,?~,S,A
If
po
+N
fr
po
+N
-A
+E,N
st
rt
If
wp
po
po
po
sc
-N
wp
po
+D,E.~
lupeol, lupeol
acetate, ursolic acid
(A, po)
toxic
nontoxic
nontoxic
nontoxic
toxic
toxic?
toxic
catharanthine
(H CI ),Iochnerine,
tetrahydroalstonine,
leurosine sulfate,
vindoline(HCI,
vindolinine(2HCI
(H,po)
toxic
nontoxic
toxic
toxic
alkaloids
toxic
vinsumine, vinervine
?
reserpine (A, H)
172
FAMILY
SCIENTIFIC NAME
ETH
ACTIVITY
Apocynaceae
Vinca minor
+A,E
Apocynaceae
Aquifoliaceae
Araliaceae
Araliaceae
Araliaceae
Araliaceae
Araliaceae
Araliaceae
Wrightia coccinea
Ilex guayusa
A canthopanax sessiliflorus
Aralia chinensis
Aralia elata
Aralia mandshurica
Aralia nudicaulis
Eleutherococcus chiisanensis
Araliaceae
Eleutherococcus senticosus
Araliaceae
Araliaceae
Oplopanax horridum
Panax ginseng
Araliaceae
-N
+S,-N
+N
-N
+A,E,G
+G,?N
PART
TESTED
fr
sb
sb
If,wp
ROtITE
ADMIN.
po
po
ACl1VE
CONSlITUENT
TOXICITY
akuammidine,
isoreserpiline,
reserpiline,
vincoamine,
vicanidine,
vinervine,
vinsumine
nontoxic
guanidine
iv
sc,po
+A,E
po
+A,B,E,N
rt
po,ip
+O,G,?N
+A,B,O,V,?
5,N,Y,-O
rb
rt,lf
po
po,ip
+U,?N
rt
po
Araliaceae
Panax pseudoginseng var.

notoginseng
Panax quinquefolius
+A,?N
rt
ip
Araliaceae
Araliaceae
Araliaceae
Aristolochiaceae
Aristolochiaceae
Aristolochiaceae
Aristolochiaceae
Aristolochiaceae
Aristolochiaceae
Aristolochiaceae
Asclepiadaceae
Asclepiadaceae
Asclepiadaceae
Asclepiadaceae
Asclepiadaceae
Asclepiadaceae
Panax repens
Schefflera capitata
Tetrapanax papyriferus
Aristolochia brevipes
Aristolochia fangchi
Aristolochia indica
Aristolochia manshuriensis
Aristolochia odoratissima
Aristolochia staheli
Aristolochia trilobata
Calotropis gigantea
Cara/luma edulis
Cryptolepis elegans
Cryptostegia grandiflora
Decalepis hamiltonii
Gymnema sylvestre
+U
-N
+5
rt
po
po
po
+S
-N
+N
rt
Asclepiadaceae
Asclepiadaceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Holostemma annularis
Periploca laevigata
Achillea fragrantissima
Achillea micrantha
Achillea millefolium
Achillea santolina
Achyrocline alata
Achyrocline satureioides
Adenostemma lavenia
Ageratum conyzoides
Ainsliaea latifolia
Ambrosia maritima
Anthemis deserti
Arctium lappa
Arnica montana
1
2
1
1
ap
wp
sb
po
po
chiisanoside
(A, po)
eleutherans a-g
(A,H,ip)
toxic
nontoxic
nontoxic
nontoxic
nontoxic
nontoxic
nontoxic
nontoxic?
nontoxic
nontoxic
ginsenoside RB-2, nontoxic
panaxans a-h, q-u
(A, H, ip) daucosterol,
nicotinic acid (A, H po),
adenosine, pyroglutamic acid
nontoxic
quinquefolans A,
B, and C
nontoxic
nontoxic
toxic
nontoxic
?
toxic
nontoxic
1
1
1
1
1
1
1
1
1
1
1
1
1
1
4
-N
-A,N
-N
-A,+N
+A,D,X,N,
5,E,G
ap
ap
po
po
po
po
toxic
toxic
If
po
toxic
rt
rt
toxic
toxic
nontoxic
-N
fI
iv
-N
wp
po
nontoxic
-N
wp
wp
wp
po
nontoxic
IV
+0
+N
+A,D,?N,-S
+N
rt
wp
sc
po
nontoxic
toxic

FAMILY
SCIENTIFIC NAME
Ern
ACTIVITY
PART
TESTED
ROUTE
ADMIN.
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Artemisia absinthium
Artemisia abyssinica
Artemisia afra
Artemisia capillaris
Artemisia dracunculus
Artemisia herba-alba
Artemisia vulgaris
Atractylis gummifera
1
1
2
+A,N
wp
po
-5
-5
+A,D,N
?N
+N
ap
ap
ap
wp
po
po
po
po
Asteraceae
Asteraceae
Atractylis ovata
Atractylodes ;aponica
+N
+A,5,N
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Atractylodes lancea
Atractylodes macrocephala
Bidens leucantha
Bidens pilosa
Brachylaena elliptica
Cacalia decomposita
Calea zacathechichi
Carthamus tinctorius
Centaurea aspera
+A
+N,-5
+A
+A
+N
+A
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Centaurea calcitrapa
Centaurea cOTCubionensis
Centaurea melitensis
Centaurea pallescens
Centaurea salmantica
Centaurea seridis
1
2
2
2
1
2
1
3
1
IV
rz
po
ip,po
rz
rz
wp
wp
po
po
po,ip
po,ip
st,rt
po,ip
-N
+N
sd
I,1f
po
po
+N
+G,N,-A
+N
I
I,1f
fl
po,iv
po
po
+N
+G
fl,wp
I,wp
iv
po
ACTIVE
CON5TmJENT
173
TOXICITY
toxic
nontoxic
nontoxic
nontoxic
toxic
carboxyattacttoxic
yloside, atractyloside
(H,iv)
toxic?
atractans a-c
(A, H, ip (glycans)
nontoxic?
?
nontoxic
toxic
nontoxic
nontoxic
lupeol,
daucosterol (A, po)
cnicin (H, iv)
nontoxic
nontoxic?
nontoxic
nontoxic?
nontoxic?
daucosterol,
nontoxic?
ursolic acid (A, po),
~sitosterol-3-~-D
-glucoside
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Centaurea soLstitialis
1
Centipeda minima
Cheirolophus arbutifolius
1
Cheirolophus canariensis
1
Chrysanthemum indicum
Chrysanthemum leucanthemum
Cichorium endivia
1
Cichorium intybus
2
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Cirsium depsacolips
Cirsium ochrocentrum
Cnicus benedictus
Coleosanthus SquaTTOSUS
Conyza canadensis
Conyza incana
Cynara scolymus
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Dahlia pinnat.l
Elytropappus rhinocerotis
1
Erigeron annuus
Erigeron canadensis
Erigeron pusillus
Eupatorium odoratum
Eupatorium pl4rpureum
Eupatorium urticaefolium
Eupatorium t'i/losum
Gnaphalium semiamplexicauie
Helianthus annuus
Helianthus tuberosus
+N
-N
I
wp
po
po
nontoxic?
?
-N
1
+N
-A,+U,?N
po
nontoxic
If
If,rt,wp
pO,sc
+N
rt
nontoxic
coumarin,
nontoxic
scopoletin (A, H, po)
?
cnicin
+N
1
1
1
nontoxic?
toxic?
+N
+E.?N
ap
I
ip
po,ip
+N
ap
po
nontoxic
+N
?N
If,st
wp
po
toxic
?
+N
+V.-N
ap
po
toxic
IV
tb
po
+N
+N
-D
oxidase
(A, H, po, ip)
nontoxic
nontoxic
nontoxic?
174
FAMILY
SCIENTIFIC NAME
Ern
Asteraceae
Inula helenium
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Inula racemosa
Inula viscosa
Ixeris dentata
Lactuca sativa
Lactuca serriola
Lapsana communis
Launea nudicaulis
Leuzea carthamoides
Matricaria aurea
Mikania micrantha
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Mulgedium alpinum
Neurolaena lobata
Parthenium hysterophorus
Puliearia fo/iolosa
Saussurea heteromalla
Schkuhria pinnata
Senecio nemoralis
Senecio tenuifolius
Siegesbeckia orientalis
Silybum marianum
Sonchus brachyotus
Sphaeranthus indicus
Stevia aristata
Stevia rebaudiana
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Taraxacum officinale
Taraxacum palustre
Terminalia ar;una
Trixis radialis
Verbesina crocata
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Asteraceae
Verbesina encelioides
Verbesina persicifo/ia
Vernonia malabarica
Vernonia volkameriaefolia
Vicoa indica
Vittadinia australis
Xanthium strumarium
Balsaminaceae
Basellaceae
Impatiens balsamina
Boussingaultia basel/oides
Berberidaceae
Berberidaceae
Berberidaceae
Berberidaceae
Betulaceae
Bignoniaceae
Bignoniaceae
Bignoniaceae
Bignoniaceae
Bignoniaceae
Bignoniaceae
Bignoniaceae
1
Berberis aristata
Berberis vulgaris
Epimedium sagittatum
Hydrastis canadensis
Alnus nepalensis
Campsis grandiflora
1
Crescentia cu;ete
1
Heterophragma quadriloClllare
1
Parmentiera edulis
Spathodea campanulata
Stereospermum suaveolens
Tecoma mol/is
1
ACI1VITY
PART
ROtITE
TESTED
ADMIN.
+U,N
po
ACTIVE
CONSTITIJENT
TOXICITY
alantolactone
(A,H,po)
toxid
nontoxic
+G,N,D,E
rt
po
+A
-A,E,?N
+N
wp
If
sd
ip
sc
po
+A,N
+B
is
+N
ab
po
+N
+A,N
wp
If
po
po
+N
-N
wp
wp
po
nontoxic
-N
+N
+N
-N
+N
wp
wp
nontoxic
nontoxic
wp
wp
po
po
po
po
po
1
1
+A,G,?N
If
po
?N,-S,A
wp
po
+D,-N
sb,ap
po
+A
l,lf
po,ip
+N
+A
-N
-N
-N
+N
+G,N
l
l,lf
ap
ap
wp
wp
rt,wp,sd
po
po,ip
po
po
po
po
po,iv,ip
1
1
+S,A
ap
po,ip
+N
-N
+N
+N,-S
+N
rt
sb
ap
rz
sb
po
po,iv
po
po
po
+N
-A
+S
+N
+D
ap
fr,rt
sb
rt
If
1
1
1
1
1
1
3
2
nontoxic
nontoxic?
nontoxic
po
coumarin,
scopoletin, lupeol
acetate (A, H po)
nontoxic?
nontoxic?
toxic
toxic
1
1
silymarin
nontoxic
toxic
stevioside (A iv),
lupeol (A, po)
1
1
1
po,ip
ip
po
pO,sc
daucosterol,
galegine, lupeol,
lupeol acetate
(A, po, ip)
carboxyatractyloside
nontoxic
nontoxic
nontoxic?
toxic
toxic?
toxic?
nontoxic
nontoxic
nontoxic
nontoxic
toxic
nor-triterpenoid
saponins
toxic
toxic
berberine
toxic
toxic
toxic
nontoxic?
nontoxic
nontoxic
nontoxic

FAMILY
SCIENTIFIC NAME
ETH
ACTIVITY
PART
TESTED
ROUTE
ADMIN.
Bignoniaceae
Tecoma stans
+D,N,?A
If,st,wp
Bixaceae
Bixa orellana
?N
ap,sd
po,ip,iv,sc tecomanine and

tecostanine
(A. H, po, iv)
po
Bombacaceae
Bombacaceae
Bombacaceae
Bombacaceae
Bombacaceae
Boraginaceae
Boraginaceae
Boraginaceae
Bernoullia flammea
Bombax malabaricum
Ceiba pentandra
Pachira aquatica
Salmalia malabarica
Cordia dichotoma
Heliotropium subulatum
Lithospermum erythrorhizon
+N
-N
fl,sb
rt,sb
po
po
+N
-N
+N
+A,N
sb
ap
wp
rt
po
po
ip
?N,-S
If,rt
po,iv
Boraginaceae
Boraginaceae
Boraginaceae
Boraginaceae
Boraginaceae
Brassicaceae
Brassicaceae
Brassicaceae
Brassicaceae
Brassicaceae
Brassicaceae
Brassicaceae
Brassicaceae
Brassicaceae
Brassicaceae
Brassicaceae
Buddlejaceae
Burseraceae
Burseraceae
Burseraceae
Cactaceae
Cactaceae
Cactaceae
Cactaceae
Cactaceae
Cactaceae
Cactaceae
Cactaceae
Campanulaceae
Campanulaceae
Campanulaceae
Cannabaceae
Capparidaceae
Ca pparidaceae
Caprifoliaceae
Lithospermum officinale
Onosma echinoides
Symphytum officinale
Tournefortia hirsutissima
Trichodesma zeylanicum
Armoracia lapathifolia
Brassica napiformis
Brassica oleracea
Brassica rapa
Descurainia sophia
Lepidium ruderale
Lepidium virginicum
Megacarpaea polyandra
Nasturtium officinale
Raphanus sativus
Sisymbrium columnae
Buddle;a officinalis
Boswellia serrata
Bursera delpechiana
Commiphora myrrha
Lophophora williamsii
Opuntia decumana
Opuntia dellenii
Opuntia ficus-indica
Opuntia inermis
Opuntia streptacantha
Opuntia vulgaris
Peniocereus greggii
Codonopsis pilosula
Codonopsis tangshen
Platycodon grandiflorum
Cannabis sativa
Capparis spinosa
Cleome droserifolia
Lonicera ;aponica
Caprifoliaceae
Caprifoliaceae
Caprifoliaceae
Caprifoliaceae
Caricaceae
Caryophyllaceae
Casuarinaceae
Celastraceae
Celastraceae
Celastraceae
Sambucus mexicana
Sambucus nigra
Viburnum acuminatum
Viburnum foetens
Carica papaya
Paronychia argentea
Casuarina equisetifolia
Catha edulis
Euonymus echinatus
Euonymus glaber
ACTIVE
CONSTITUENT
175
TOXICITY
toxid
nontoxic
toxic
1
1
1
+N
toxic
toxic
lithospermans a-c toxic
(A, H, ip glycans)
nontoxic
po
toxic
nontoxic
nontoxic
nontoxic
nontoxic
nontoxic
toxic?
nontoxic
nontoxic?
nontoxic
nontoxic
nontoxic
nontoxic?
nontoxic?
?
nontoxic
nontoxic
toxic
toxic
nontoxic
-N
wp
po
-E,+P,G,?N
+N
+N
+A,E
If
rt
wp
po,sc
po
po
po
+N
wp
po
-N
-N
wp
wp
po
po
+N,-S
-N
+S,N
+N
-N
-N
+N,?D
?D,-G
+D,?G,-P,A,N
+U,N
fr,st,gm
st
gm
po
po
po
ap
fr
wp
If
st
wp
po
po
po
po
po
po
-S
rt
po
+A
+U,?N
rt
fl,lf,rn
po
po,in,sc
1
1
1
+N
ap
po
-N
-N,S
-N
-N
?N
fl
IV
ap
ap
fr,ap
po
po
po
po
nontoxic
nontoxic
nontoxic
nontoxic
+N
-N
-N
-N
ap
If,st
ap
ap
po
po
po
po
nontoxic
toxic
toxic
?
1
1
glucokinin
lepidine (A, po)
3
1
1
1
1
3
1
1
1
1
1
1
1
1
pectin (A, po)
nontoxic
nontoxic?
daucosterol,
scopoletin, ursolic
acid (A, po)
toxic
nontoxic
?
nontoxic
176
FAMILY
SCIENTIFIC NAME
ETH
ACIlVITY
PART
TESTED
ROmE
ADMIN.
ACTIVE
CONSTITUENT
Celastraceae
Celastraceae
Chenopodiaceae
Chenopodiaceae
Chenopodiaceae
Euonymus indicus
Hippocratia macrantha
Atriple:c halimus
Beta vulgaris
Hammada salicomica
N
N
+D,A,N
+N
+A,-N
ap
ap
If
ap,rt
ap,wp
po
po
po
pO,sc
po,iv
Cr, Mn (A, po)
Chenopodiaceae
Clusiaceae
Clusiaceae
Clusiaceae
Spinacia oleracea
Gareinia cola
Garcinia indica
Garcinia mannii
+N
+A
ap
sd
ap
po
ip
po
po
Clusiaceae
Cneoraceae
Combretaceae
Combretaceae
Combretaceae
Combretaceae
Combretaceae
Connaraceae
Convolvulaceae
Convolvulaceae
Convolvulaceae
Convolvulaceae
Convolvulaceae
Convolvulaceae
Convolvulaceae
Convolvulaceae
Convolvulaceae
Convolvulaceae
Convolvulaceae
Convolvulaceae
Convolvulaceae
Cornaceae
Cornaceae
Garcinia pedunculata
Neochamaelea pulverulenta
Anogeissus pendula
Conocarpus erectus
Terminalia bellerica
Terminalia catappa
Terminalia chebula
Rourea santaloides
Argyreia cuneata
Argyreia involucrata
Argyreia nervosa
Calystegia japonica
Convolvulus microphyllus
Ipomoea aquatica
Ipomoea batatas
Ipomoea nil
Ipomoea purpurea
Me"emia mammosa
Porana paniculata
Quamoclit coccinea
Rivea ornata
Comus mas
Comus officinalis
Crassulaceae
Crassulaceae
Crassulaceae
Cucurbitaceae
Cucurbitaceae
Bryophyllum pinnatum
Rhodiola rosea
Sedum formosanum
Benincasa hispida
Bryonia alba
Cucurbitaceae
Cucurbitaceae
Cucurbitaceae
Cucurbitaceae
Bryonia cretica
Bryonia dioica
Bryonia epigaea
Citrullus co/ocynthis
1
3
Cucurbitaceae
Cucurbitaceae
Cucurbitaceae
Cucurbitaceae
Citrullus Ianatus
Coccinia cordifolia
Coccinia grandis
Coccinia indica
1
1
1
3
Cucurbitaceae
Cucurbitaceae
Cucurbitaceae
Cucurbitaceae
Cucurbitaceae
Cucurbitaceae
Cucurbitaceae
Cucumis melo
Cucumis sativus
Cucurbita maxima
Cucurbita moschata
Cucurbita pepo
Lagenaria siceraria
Lagenaria vulgaris
N
+U
N
ap
po
ap
po
TOXICITY
nontoxic
nontoxic
N-methyltrypttoxic
amine, scopoletin
(A,H,po)
nontoxic
manniflavanone
(A,po)
1
1
1
1
2
1
1
1
1
1
1
1
1
1
1
1
nontoxic
+N
fr,sb
po
?A,D,-N
N
-N
If
ap
If
po,sc
po
po
+N
+N
-N
wp
po
-N
+N
N
ap
ap
sp
po
po
po
?S,Y,G,N
fr
po
+U
1
1
2
1
toxic
?
nontoxic
toxic
toxic?
1
1
1
nontoxic
sc
N,S,G
+A
wp
rt
po
im
-N
-A,N
rt
po
+N
wp
po
rt,fr
po
+D,S,G,K,T,
?A,N,X
-N,G,S
-N,G,S
fr,lf,st,rt
po
wp
wp
po
po
-S
sd
po
+D
-N
fr
po
toxic
nontoxic
toxic
nontoxic
ursolic acid
(A, po), oleanolic
acid
nontoxic
toxic?
nontoxic
toxic?
toxic
trihydroxyoctadec toxic
adienoic acid
toxic
toxic
toxic?
toxid
nontoxic
toxic?
nontoxic?
nontoxic?
quaternary
nontoxic
alkaloid (? (H, po)
toxic
toxic?
toxic?

FAMILY
SCIENTIFIC NAME
Cucurbitaceae
Luffa acutangula
Cucurbitaceae
Cucurbitaceae
Cucurbitaceae
Cucurbitaceae
Luffa echinata
Melothria heterophylla
Momordica balsam ina
Momordica charantia
1
1
12
Cucurbitaceae
Cucurbitaceae
Momordica cochinchinensis
Momordica foetida
Cucurbitaceae
Cucurbitaceae
Cucurbitaceae
Cucurbitaceae
Cucurbitaceae
Cucurbitaceae
Cuscutaceae
Datiscaceae
Dipsacaceae
Dipterocarpaceae
Dipterocarpaceae
Dipterocarpaceae
Ebenaceae
Ebenaceae
Elaeagnaceae
Elaeocarpaceae
Elaeocarpaceae
Ericaceae
Ericaceae
Ericaceae
Ericaceae
Ericaceae
Ericaceae
Ericaceae
Trichosanthes anguina
Trichosanthes bracteata
Trichosanthes cucumeroides
Trichosanthes dioica
Trichosanthes kirilowii
Trichosanthes multiloba
Cuscuta sp.
Datisca cannabina
Dipsacus asperoides
Dipterocarpus indicus
Vateria indica
Vatica chinensis
Diospyros insignis
Diospyros peregrina
Elaeagnus conferta
Elaeocarpus ganitrus
Elaeocarpus serratus
Agapetes sikkimensis
Arbutus menziesii
Arctostaphylos uva-ursi
Rhododendron campanulatum
Vaccinium corymbosum
Vaccinium leschenaultii
Vaccinium myrtillus
Ericaceae
Ericaceae
Ericaceae
Eucommiaceae
Euphorbiaceae
Euphorbiaceae
Euphorbiaceae
Euphorbiaceae
Vaccinium oxycoccus
Vaccinium pennsylvanicum
Vaccinium vitis-idaea
Eucommia ulmoides
Acalypha wilkesiana
Aporosa lindleyana
Blachia umbellata
Bridelia ferruginea
Euphorbiaceae
Cluytia richardiana
Euphorbiaceae
Euphorbiaceae
Euphorbiaceae
Euphorbiaceae
Euphorbiaceae
Euphorbiaceae
Euphorbiaceae
Croton caudatus
Croton niveus
Drypetes venusta
Euphorbia helioscopia
Euphorbia hirta
Euphorbia pilulifera
Euphorbia prostrata
177
ACIlVITY
PART
TESTED
ROUfE
ADMIN.
AcnvE
CONSTITIJENT
+N
ap
po
+N
ap
po
?A,S,D,
G,N,=X
fr,sd
po,sc,iv
toxic/
nontoxic
toxic
toxic
nontoxic?
polypeptide p
toxic/
(A, sc), charantin: nontoxic
daucosterol + 5,25stigmastadien-3pol-glucoside
(A,H,po)
+s
+A
tb
ip
ip
-N,G,S
+N
wp
wp
po
+G,N,-S
+A,N
ap,rr,sd
fr,rr,tb
po
po
-s
+N
-s
-N
-N
-N
-N
-N
-N
+N
-N
+N
sd
wp
rr
ap
ap
ap
ap
ap
ap
sb
ap
ap
po
po
po
po
po
po
po
po
po
po
po
po
-s
-N
+D,-N
+N
+D,A,G,P,N
If
ap
If
ap
ap,lf
po
po
po
po
po,sc,iv
If
If
st,lf
ap
wp
ap
If
po,iv
+N
+D,P,G
+N
?A,S
-N
+N
-N
+D,G,-A
+A,N
1
1
-N
-N
-N
-u
+u
+u
-A.+N
ETH
foetidin =
charantin (A, ip)
1
2
toxic?
nontoxic?
nontoxic?
nontoxic
nontoxic?
nontoxic?
1
2
1
TOXICITY
neomyrrillin
(A,H,po),
(-)epicatechin
(A,ip)
nontoxic
toxic
nontoxic
nontoxic
toxic
nontoxic
toxic
toxic
nontoxic
toxic
nontoxic
toxic
nontoxic
nontoxic
nontoxic
nontoxic?
nontoxic?
po
po
po
po
po
ip
fr
po
ap
ap
wp
po
po
po
ap
po
toxic
toxic
toxic
rutin (quercetin-3neohesperidoside ),
daucosterol (A, po)
saudin (A, ip)
(diterpene)
nontoxic?
toxic
toxic
nontoxic
toxic
toxic?
toxic?
daucosterol,
toxic?
lupeol, ursolic acid
(A,po)
178
FAMILY
SCIENTIFIC NAME
Euphorbiaceae
Euphorbiaceae
Euphorbiaceae
Euphorbiaceae
Euphorbiaceae
Euphorbiaceae
Euphorbiaceae
Euphorbiaceae
Euphorbiaceae
Euphorbiaceae
Euphorbiaceae
Glochidion heyneanum
Glochidion hohenackeri
Glochidion sphaerogynum
Jatropha curcas
Jatropha gossypiifolia
Mallotus philippinensis
Phyllanthus amarus
Phyllanthus emblica
Phyllanthus epiphyllanthus
Phyllanthus lawii
Phyllanthus niruri
Eu phorbiaceae
Euphorbiaceae
Euphorbiaceae
Euphorbiaceae
Euphorbiaceae
Euphorbiaceae
Euphorbiaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Phyllanthus sellowianus
Putran;iva roxburghii
Ricinus communis
Sapium sebiferum
Securinega leucopyrus
Securinega virosa
Tragia involucrata
Abrus precatorius
Acacia arabica
Acacia benthami
Acacia catechu
Fabaceae
Acacia confusa
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Acacia ferruginea
Acacia melanoxylon
Acacia modesta
Acacia nilotica
Acacia senegal
Acacia suma
Adenanthera pavonina
Aeschynomene indica
Albizia ;ulibrissin
Albizia lathamii
Albizia lebbek
Albizia moluccana
Albizia odoratissima
Albizia procera
Albizia stipulata
Alhagia maurorum
Arachis hypogaea
Astragalus candolleanus
Astragalus membranaceus
Atylosia lineata
Atylosia platycarpa
Atylosia volubilis
Bauhinia aculeata
Bauhinia candicans
Bauhinia emarginata
Bauhinia forficata
Fabaceae
Fabaceae
Fabaceae '
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Bauhinia manca
Bauhinia purpurea
Bauhinia retusa
Bauhinia variegata
Bowdichia virgilioides
Butea monosperma
Caesalpinia bonducella
ETH
ACTIVITY
PART
TESTED
ROlTfE
ADMIN.
-N
+N
-N
-N
ap
ap
ap
ap
po
po
po
po
+N
fr
po
-N
sd
po
-N
+A,?N
ap
If
po
po
+N
sb
IV
+N
-N
-N
+N
-N
?N
-N
-A,?N
-A,?N
rt,wp
ap
ap
sd
ap
ap
sb
sb,sd
sd,gm
po
po
po
po
po
po,sc
po
po
po
ACTIVE
CONSTIrUENT
2
4
1
4
1
1
1
1
1
1
1
1
1
1
-N
+A,N
-A,+N
-A,+N
-N
-A,+N
-N
-N
-N
-N
?N
-A,+N
-A,?N
-N
-A,+N
-N
+N
-N
+A,?N,-S
-N
-N
-N
sb
sd
sd
sd,gm
sb
sd
ap
wp
ap
ap
fr,rt,sb
sd
sd,sb
ap
sd
wp
sd
wp
rt
wp
wp
ap
po
po
po
po
po
+A,?N
If
po
+A,P,D,N
wp
po
+G
+A,N
+N
If
sd
fl
po
-N
If
po
toxic
toxid
nontoxic
toxic
toxic
nontoxic
nontoxic
nontoxic
nontoxic
nontoxic
nontoxic
toxic
nontoxic
toxic
toxic
toxic
toxic
toxic
toxic
nontoxic
nontoxic
nontoxic?
nontoxic?
nontoxic
toxic
nontoxic
po
po
po
po
po
po
po
po
po
po
po
po
po
daucosterol,
lupeol, pectin
(A, po)
quercetin
2
2
toxic
toxic
nontoxic
toxic
toxic
nontoxic
toxic
toxic
toxic
toxic
toxic
toxic
toxic
toxic
toxic
nontoxic
thioglycosides
toxic
toxic
precatorine (H, sci nontoxic
N-methyltryptamine (H, po)
+N
1
1
lupeol, lupeol
acetate (A, po)
TOXICITY
nontoxic
nontoxic
toxic
nontoxic
?

FAMILY
SCIENTIFIC NAME
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Caesalpinia coriaria
Caesalpinia digyna
Ca;anus ca;an
Canavalia ensiformis
Caragana brevispina
Cassia alata
Cassia auriculata
Cassia fIStula
Cassia {ruticosa
Cassia ;avanica
Cassia occidentalis
Cassia sophera
Cassia surattensis
Cassia tamala
Cassia tora
Castanospermum australe
Ceratonia siliqua
Cicer arietinum
Crotalaria medicaginea
Crotalaria retusa
Crotalaria verrucosa
Cyamopsis tetragonolobus
Dalbergia spinosa
Dalbergia sympathetica
Derris scandens
Dolichos biflorus
Do/ichos lablab
Entada scandens
Erythrina indica
Erythrina sigmoidea
Fabaceae
Fabaceae
Fabaceae
Erythrina suberosa
Eysenhardtia polystachya
Galega officinalis
Fabaceae
Fabaceae
Fabaceae
Gliricidia sepium
Glycine max
Glycyrrhiza glabra
Ern
1
2
2
1
1
2
1
2
ACITVITY
PART
TESTED
ROtITE
ADMIN.
ACTIVE
CONSTITUENT
-N
-N
+N
+N
+N
+5,?N
?A,N
-A,?N
ap
rt
sd
sd
ap
ap,lf
fl,lf,sd
fr,sd,sb
po
po
po
iv
po
po
toxic
toxic
nontoxic
canatoxin (protein) toxic
nontoxic
?
po
-N
+N,-5
-N
-N
+D
-5
+F
+D
+N,G
-N
-N
-N
+A,D,G,N
-N
-N
-N
+N
+A,D,E,G,N
-N
ap
If
sd,sb
ap
po
po
po
po
sd
is
po
po
po
po
po
po
po
po
po
po
po
po
po
po
sd
fr
wp
ap
wp
fr,gm,sd
ap
ap
ap
sd
fr,sd
ap
1
po
+N
1
2
+N
+A
+D,A,G,N
sb
wp
If
po
po,ip
po,ip
ap
ap
rt
po
-N
+N
?N,5,Y
ip,po
TOXICITY
toxic
toxic
?
toxic
?
toxic
castanospermine
nontoxic
nontoxic
toxic
toxic
toxic
guar gum (H, po) nontoxic
?
toxic
?
toxic
toxic
toxic
toxic
sigmoidin b,c
(flavanones)
toxic
galegine
(isoamyleneguani
dine) (A, po, ip)
~-glycyrrherinic
toxic
toxic
nontoxic
nontoxic
acid
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Humboldtia brunonis
lndigofera arrecta
lndigofera glandulosa
lndigofera mysorensis
lndigofera spinosa
lndigofera tinctoria
Lathyrus ;aponicus
-N
+D
-N
-N
ap
po
wp
ap
po
po
+N
+A
ap
sd
nontoxic
?
nontoxic
toxic
179
nontoxic
lathyrine,
L-glutamylL-Iathyrine
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Lathyrus palustris
Lathyrus sativus
Leucaena glauca
Leucaenaleucocephala
Lupinus albus
+N
+D,N
+A,E,P,N
+N
+G,Z,N,-A,S
Fabaceae
Lupinus termis
+A,G,:E,?S,N sd
po,sc
Fabaceae
Medicago sativa
+S,?N
If
po
Fabaceae
Mezoneuron cucullatum
-N
ap
po
If
sd
sd
sd
sd,wp
po
po,ip
po
po
toxic?
toxic?
toxic
toxic
lupanine, sparteine toxic

(A, po)
lupanine,
toxic
coumarin, sparteine
(A, po)
Mn ions (H, po),
vitamin K
nontoxic
toxic
180
R.
J. Maries and N. R. Farnsworth
FAMILY
SCIENTIFIC NAME
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Milletia cinerra
Milletia kit;ana
Mimosa pudica
Moghania paniculata
Mucuna imbricata
Mucuna pruriens
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Ononis pubescens
Parkia speciosa
Parkinsonia aculeata
Phaseolus aureus
Phaseolus coccineus
Phaseolus vulgaris
Pisum sativum
Pithecellobium bigeminum
Pithecellobium lobatum
Pongamia pinnata
Prosopis farcata
Prosopis ;uliflora
Psoralea pubescens
Pterocarpus marsupium
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Fabaceae
Pterocarpus santalinus
Pueraria hirsuta
Pueraria lobata
Pueraria tuberosa
Robinia pseudacacia
Samanea saman
Saraca indica
Securigera securidaca
Smithia conferta
Sophora angustifolia
Spartium ;unceum
Sweetia panamensis
Tamarindus indica
Tephrosia purpurea
Tephrosia villosa
Teramnus labialis
Tetrapleura tetraptera
Trifolium alexandrinum
Trifolium pratense
Trigonel/a foenum-graecum
Fabaceae
Fabaceae
Fabaceae
Fagaceae
Fagaceae
Fagaceae
Fagaceae
Fagaceae
Fagaceae
Fagaceae
Fagaceae
Fagaceae
Flacourtiaceae
Uraria picta
Vicia faba
Vigna mungo
Castanea dentata
Fagus sylvatica
Quercus boissieri
Quercus ilicifolia
Quercus infectoria
Quercus Iamel/osa
Quercus Ianceaefolia
Quercus lineata
Quercus spicata
Aphloia theiformis
ETH
ACTIVITY
PART
TESTED
-V,N
ap
+A
-N
-N
?N,-A
wp
ap
ap
fr,rt,sd
po
po
po
po
+N
ap
ip
-N
+G
ap
sd
po
po
+N,G,?D,-S
+N
-N
-N
?N
sd
po
ap,sd
sd
fl
po
po
po
-N
ap
po
+A,D,X,G,N
st,sb
po
+S,N
+N
+0
+N
-N
-N
-N
?N
-N
+S
st,sd
rt
fl
tb
ap
ap
ap,fl
sd
wp
rt
po
po
po
po
po
po
po
nontoxic
toxic
toxic
nontoxic
po
nontoxic
ROUTE
ADMIN.
ACTIVE
CONS1TI1JENT
TOXICITY
toxic
nontoxic
toxid
nontoxic
1
2
2
1
1
1
1
1
2
1
1
1
2
1
1
1
1
1
4
glucokinin
nontoxic?
nontoxic
toxic
toxic?
nontoxic?
nontoxic
(-)epicatechin
(A, ip); kino gum
(H, po); pterostilbene (H, po)
nontoxic
nontoxic?
nontoxic?
po
+A,N
-N
+N
sd
If
wp
po
po
po
+A,D,N
-N
+A,D,G,N,?S
sd
wp
sd,wp
po
po
po
-N
wp
po
+A
-S
sd
sd
po
po
3
1
1
1
1
toxic?
nontoxic
lupeol (A, po)
toxic
toxic
nontoxic
toxic
toxic?
nontoxic
toxic
nontoxic
nontoxic
nontoxic
trigonelline,
coumarin, nicotinic
acid (A, H, po),
nicotinamide (H, po),
fenugreekine (H, iv)
nontoxic
nontoxic
nontoxic
?
+N
+N
+N
+N
+N
gl
sb
sb
sb
sb
po
po
po
po
po
nontoxic
toxic
toxic
toxic
toxic

FAMILY
SCIENTIFIC NAME
ETH
ACI1VITY
PART
TESTED
ROUTE
ADMIN.
Flacouniaceae
Flacourtiaceae
Flacourtiaceae
Flacourtiaceae
Fumariaceae
Fumariaceae
Gentianaceae
Gentianaceae
Gentianaceae
Gentianaceae
Gentianaceae
Gentianaceae
Gentianaceae
Gentianaceae
Gentianaceae
Casearia esculenta
Casearia glauca
Flacourtia montana
Hydnocarpus alpina
Corydalis govaniana
Fumaria parviflora
Cans cora decussata
Centaurium erythraea
Centaurium spicatum
Enicostema hyssopifolium
Enicostema littorale
Exacum bicolor
Gentiana lutea
Nymphoides oristatum
Swertia chirayita
1
1
?N,-D
-N
-N
-N
-N
-A,+N
rt,sb
sb
ap
ap
wp
ap
po
po
po
po
po
po
Geraniaceae
Geraniaceae
Geraniaceae
Globulariaceae
Goodeniaceae
Hippocrateaceae
Hippocrateaceae
Hippocrateaceae
Hippocrateaceae
Hippocrateaceae
Hydrophyllaceae
Hypericaceae
Ixonanthaceae
Juglandaceae
Krameriaceae
Lamiaceae
Lamiaceae
Lamiaceae
Lamiaceae
Lamiaceae
Lamiaceae
Geranium maculatum
Geranium nepalense
Geranium sp.
Globularia alypum
Scaevola taccada
Salacia chinensis
Salacia {ruticosa
Salacia macrosperma
Salacia prinoides
Salacia reticulata
Hydrolea zeylanica
Hypericum uliginosum
Irvingia gabonensis
Juglans regia
Krameria triandra
Ajuga bracteosa
Ajuga iva
Calamintha macrostema
Calamintha umbrosa
Cedronella canariensis
Coleus forskohlii
Lamiaceae
Lamiaceae
Lamiaceae
Lamiaceae
Lamiaceae
Lamiaceae
Lamiaceae
Lamiaceae
Lamiaceae
Lamiaceae
Lamiaceae
Lamiaceae
Lamiaceae
Lamiaceae
Lamiaceae
Lamiaceae
Lamiaceae
Lamiaceae
Lamiaceae
Lamiaceae
Lamiaceae
Lamiaceae
Dysophylla rugosa
Gomphostemma parviflorum
Hyptis suaveolens
Lavandula dentata
Lavandula latifolia
Lavandula multifida
Lavandula stoechas
Leonotis leonurus
Lycopus virginicus
Marrubium deserti
Marrubium vulgare
Mesona procumbens
Ocimum canum
Ocimum gratissimum
Ocimum micranthum
Ocimum sanctum
Origanum syria cum
Orthosiphon grandifloms
Orthosiphon spiralis
Perilla frutescens
Prunella vulgaris
Salvia canariensis
3
1
2
1
1
1
ACTIVE
CONSTITUENT
nontoxic
nontoxic
toxic
?
toxic?
nontoxic?
?X,-N
+D,X
-N
wp
ap
po
po
-N
+N,G
wp
wp
po
po
+N
-N
wp
po
1,8-dihydroxy3, 5-dimethoxyxanthone
1
1
1
2
1
1
2
TOXICITY
nontoxic?
181
nontoxic
nontoxic
nontoxic
nontoxic
nontoxic
nontoxic
toxic?
+N
+N
+G,N
+N,S,G
+N
!f,rt
rb
rb
wp
po
po
po
+D
+A
-N
-N
sd
!f
rt
po
sc
po
+A
+N
st,rt
wp
po,ip
po
+G
rt
IV
-N
-N
+N
+G,-A
-G,A
-N
+G,N,-A
wp
wp
ap
wp
wp
fl
fl
po
po
po
po
po
po
po
lupeol (A, po)
toxic
toxic
toxic?
toxic
1
3
3
1
nontoxic
nontoxic
nontoxic
ursolic acid (A, po) toxic?
ursolic acid (A, po) toxic
1
1
1
1
1
1
1
1
3
1
2
1
forskolin (A, H, iv)

(diterpene)
nontoxic
toxic
toxic
toxic
+N
nontoxic
ursolic acid (A, po)
+V
+D
-N
sd, wp
wp
po
po
+N
If
po
+D
+D
-N
-S
If
If
wp
ap
po
po
po
nontoxic
nontoxic?
nontoxic
nontoxic?
ursolic acid (A, po)
182

SCIENTIAC NAME
ETH
ACfIVfIY
PART
TESTED
ROUfE
ADMIN.
Lamiaceae
Lamiaceae
Lamiaceae
Lamiaceae
Lamiaceae
Lamiaceae
Lamiaceae
Lamiaceae
Lamiaceae
Lamiaceae
Lamiaceae
Lardizabalaceae
Lauraceae
Lauraceae
Lauraceae
Lauraceae
Lauraceae
Lauraceae
Lauraceae
Lauraceae
Lauraceae
Lauraceae
Lecythidaceae
Leeaceae
Leeaceae
Linaceae
Loganiaceae
Loganiaceae
Loganiaceae
Loganiaceae
Loganiaceae
Loganiaceae
Loganiaceae
Loganiaceae
Salvia fruticosa
Salvia lavandulaefolia
Salvia officinalis
Salvia plebeia
Salvia sclarea
Scutellaria baicalensis
Sideritis pus ilia
Teucrium oliverianum
Teucrium polium
Teucrium royleanum
Thymus serpyllum
Akebia quinata
Actinodaphne hookeri
Actinodaphne madraspatana
Cinnamomum camphora
Cinnamomum cassia
Cinnamomum sulphuratum
Cinnamomum tamala
Laurus nobilis
Persea americana
Persea gratissima
Sassafras albidum
Barringtonia acutangula
Leea crispa
Leea indica
Hugonia mystax
Anthocleista d;alonensis
Anthocleista kerstingii
Anthocleista nobilis
A nthocleista rhizophoroides
Anthocleista vogelii
Gelsemium sempervirens
Strychnos nux-vomica
Strychnos potatorum
1
1
2
-A
+A,G,N
-N,S
-N
If
fl
If
wp
po
po
po
po
?Y,-S
rt
po
+A
+U,S,N
+N
ap
ap,wp
wp
po
po
po
-N
-N
-N
+N,?Y
-N
+D,-5
+N
If
If
ap
sb
If,sb
sb,rt
If
po
po
po
po
po
po
Loranthaceae
Loranthaceae
Loranthaceae
Loranthaceae
Lythraceae
Lythraceae
Lythraceae
Lythraceae
Magnoliaceae
Magnoliaceae
Malvaceae
Malvaceae
Loranthus curviflorus
Loranthus parasiticus
Psittacanthus calyculatus
Viscum album
Lagerstroemia parviflora
Lagerstroemia speciosa
Lythrum salicaria
Sonneratia ape tala
Michelia champaca
Talauma ovata
Abelmoschus edulis
Abelmoschus glutinotextilis
Malvaceae
Abelmoschus manihot
Malvaceae
Malvaceae
Abutilon trisulcatum
Althaea officinalis
Malvaceae
Malvaceae
Malvaceae
Malvaceae
Decaschistia crotonifolia
Gossypium herbaceum
Hibiscus hirtus
Hibiscus syriacus
Malvaceae
Malvaceae
Hibiscus tiliaceus
Malachra alceifolia
FAMILY
1
1
1
1
2
1
1
1
ACTIVE
CONSTITUENT
TOXICITY
nontoxic
nontoxic
toxic
nontoxic
nontoxic
toxic
toxic
nontoxic
toxic
cinnamaldehyde
nontoxic
nontoxic
nontoxic
toxic
nontoxic
nontoxic?
1
1
+N
+N
+N
-N
rt
ap
If
ap
+N
+N
+A,N
+N
-N
-N
sb
sb
rt
po
po
po
toxic
?
toxic
toxic
2
2
2
2
1
1
2
1
nontoxic
nontoxic
po
fr
If,sb,sd
po,iv
?A
-5
+A
+N,-S
+N
+A,-U,?N
+G,S,E,A,?N
-N
+N
-N,G,A
+N
+N
fl
wp
ap
ap
ap
If,sd
fl,rt,st
ap
sb
po
po
po,ip
po
po
po,iv
po,iv
po
po
fr.rt
rt
po
po
+N
rt
po
+N
If.rt
po
-N
+A,N
-N
+N
wp
If
wp
If
po
po
po
po
+N
ap
toxic
toxic
toxid
nontoxic
?
toxic
toxic
toxic
nontoxic
toxic
toxic
toxic
okra-mucilages F,R nontoxic
abelmoschusnontoxic
mucilage G
abelmoschusmucilage M
nontoxic
nontoxic
althaeanontoxic
mucilage 0, althaeamucilage OL
toxic
toxic
nontoxic
hibiscusnontoxic
mucilage SL
nontoxic?

FAMILY
SCIENTIFIC NAME
Malvaceae
Malvaceae
Melastomataceae
Melastomataceae
Meliaceae
Meliaceae
Mallia lIerticillata
Sida spinosa
Memecylon umbellatum
Osbeckia octandra
Amoora wallichi
Azadirachta indica
Meliaceae
Meliaceae
Meliaceae
Menispermaceae
Menispermaceae
Menispermaceae
Menispermaceae
Menispermaceae
Menispermaceae
Menispermaceae
Menispermaceae
Menispermaceae
Menispermaceae
Menispermaceae
Moraceae
Moraceae
Moraceae
Moraceae
Moraceae
Moraceae
Moraceae
Moraceae
Carapa granatum
Cedrela toona
Dysoxylum binectariferum
Anamirta cocculus
Cissampelos pareira
Cocculus cordifolius
Cocculus hirsutus
Fibraurea chloroleuca
Sciadotenia amazonica
Sciadotenia toxifera
Stephania glabra
Tinospora cordifolia
Tinospora crispa
Tinospora tuberculata
Artocarpus altilis
Artocarpus integrifolia
Cecropia mexicana
Cecropia obtusifolia
Cecropia peltata
Cecropia surinamensis
Ficus asperrima
Ficus benghalensis
Moraceae
Moraceae
Moraceae
Moraceae
Moraceae
Moraceae
Ficus ben;amina
Ficus callosa
Ficus carica
Ficus glomerata
Ficus hispida
Ficus racemosa
Moraceae
Moraceae
Moraceae
Ficus religiosa
Ficus talbotii
Humulus lupulus
Moraceae
Morus alba
Moraceae
Moraceae
Moraceae
Morus australis
Morus bombycis
Morus lIigra
183
Ern
ACTIVITY
PART
TESTED
ROUTE
ADMIN.
ACl1VE
CONSTIruENT
sd
wp
1
ap
st
If,sd
ip
po
po
po
+N
+N
+N
+G,N
N
+A,E,X,S,?N
N
+N
-N
-N
ap
If
fr
ap
po
po
po
po
polysaccharide, pectin
toxic
nontoxic
nontoxic
toxic
nimbidin,
nontoxic
daucosterol
(A, H, po), other
active flavonol
glycosides
nontoxic
toxic
toxic
toxic
?
-N
-N
wp
ap
po
po
+N
+N
+A,G,-N
rt
st
st
po
1
1
po,iv
1
1
1
2
1
TOXICITY
nontoxic
toxic
toxic
toxic
po
po,iv
1
2
toxic?
toxic?
+D,N
If
po
+A,P
-N
If,st
1
po,ip,iv
-N
+D,N,G,?A,P
ap
sb,sp
po
-N
-N
ap
ap
po
po
+N
-N
?A,N,-S
sb
ap
sb,wp,fr
po
po
+A,X,?N
-N
+D,?S,-N
rb,rt
ap
If
po
+D,S,E,F,
G,N,?A
If,rb
po,sc,ip
If
po
po
1
1
2
1
1
2
1
2
+N
+D,N
po
po
po
po
toxic
?
toxic
bengalenoside
nontoxic?
(flavonoid-glycosi
de), daucosterol,
lupeol, scopoletin
(A,H,po)
nontoxic?
toxic
toxic?
nontoxic?
daucosterol,
toxic
lupeol, lupeol
acetate (A, po)
daucosterol (A, po) nontoxic?
nontoxic?
humulone,
nontoxic
lupulone (+S, po)
phytosterol
nontoxic
glycosides.
scopoletin
(A, H, po); moran a
(A,H,ip)
glycoprotein.
moranoline
nontoxic
nontoxic?
phytosterol
glycosides.
scopoletin
(A,H,po)
nontoxic
184
FAMILY
SCIENTIFIC NAME
ETH
ACTIVITY
PART
TESTED
ROUTE
ADMIN.
Moraceae
Moraceae
Moringaceae
Myrsinaceae
Myrsinaceae
Myrsinaceae
Myrsinaceae
Myrtaceae
Myrtaceae
Myrtaceae
Myrtaceae
Myrtaceae
Myrianthus arboreus
Plecospermum spinosum
Moringa pterygosperma
Aegiceras corniculatum
Ardisia neriifolia
Embelia viridiflora
Myrsine africana
Aulomyrcia hostmanniana
Eucalyptus alba
Eucalyptus citriodora
Eucalyptus c10eziana
Eucalyptus globulus
+D
-N
+A,-N
-N
-N
-N
-N
sb
ap
fr,lf,st
ap
ap
ap
wp
po
po
po
po
po
po
po
-N
+A,N
-N
-D,N,+A,S
ap
If
ap
If
po
po
po
po,ip
Myrtaceae
Myrtaceae
Myrtaceae
Myrtaceae
Myrtaceae
Myrtaceae
Myrtaceae
Myrtaceae
Myrtaceae
Myrtaceae
Myrtaceae
Eucalyptus robusta
Eugenia jambolana
Eugenia uniflora
Jambosa Iaeta
Myrtus communis
Pimenta officinalis
Psidium guajava
Syzygium alternifolium
Syzygium aromaticum
Syzygium cerasoides
Syzygium cumini
+S,-G
-N
-N
+S
+N
+A,D,?N
sd
If
ap
If,st
po
po
po
po
ap,fr,lf
po,ip
+S,-N
+N
+A,D,?N,S
sh,ap
ap
ap,sd
po
po
antimellin
(glycoside)
Myrtaceae
Myrtaceae
Myrtaceae
Nyctaginaceae
Nyctaginaceae
Nyctaginaceae
Nymphaeaceae
Nymphaeaceae
Nymphaeaceae
Oleaceae
Oleaceae
Oleaceae
Oleaceae
Syzygium hemisphericum
Syzygium jambos
Syzygium montanum
Bougainvillea spectabilis
Salpianthus arenarius
Salpianthus macrodontus
Nelumbo nucifera
Nymphaea lotus
Nymphaea nouchali
Forsythia suspensa
Jasminum rigidum
Jasminum rottlerianum
Olea europaea
-N
ap
po
-N
+A,G,N
+A
ap
If
fi
po
po
po,ip
toxic
toxic
nontoxic
pinitol (+A,N, po) nontoxic
+G,E;-N,S
+N
?N
+S
-N
-N
+U,N
fi;rz,sd
wp,rt
fr
ap
ap
If
po
po
po
po
po
po
po
Oleaceae
Onagraceae
Onagraceae
Onagraceae
Orobanchaceae
Orobanchaceae
Oxalidaceae
Oxalidaceae
Oxalidaceae
Oxalidaceae
Oxalidaceae
Paeoniaceae
Paeoniaceae
Paeoniaceae
Paeoniaceae
Papaveraceae
Papaveraceae
Papaveraceae
Papaveraceae
Passifioraceae
Pedaliaceae
Piperaceae
Olea polygama
Epilobium hirsutum
Epilobium royleanum
Fuchsia magellanica
Aeginetia indica
Cistanche tubulosa
Averrhoa bilimbi
Averrhoa carambola
Biophytum sensitivum
Oxalis corniculata
Xanthoxalis corniculata
Paeonia albiflora
Paeonia emodi
Paeonia moutan
Paeonia obovata
Argemone mexicana
Chelidonium majus
Glaucillm f1avum
Papaver somniferum
Passiflora quadrangularis
Sesamum indicum
Heckeria subpeltata
-N
ap
po
+N
-N
wp
ap
po
po
+N
+N
-N
wp
If
ap
+N
+G,N
+S,?Y
-N
+G,L,N,?Y,-S
+N
-N
+N;-S,N
+G,N,-A
+N
If,st
wp
ACTIVE
CONSTITUENT
TOXICITY
nontoxic
nontoxic
toxic
toxic
toxic
toxic
5
1
1
1
1
myrtillin
calyptoside
(A, H, po)
nontoxic
brahmic acid
1
1
1
1
toxic
nontoxic
nontoxic
nontoxic
rt
nontoxic
nontoxic
nontoxic
nontoxic
nontoxic?
nontoxic
nontoxic
nontoxic
toxic?
toxic
scopoletin
(A,H,po)
nontoxic
nontoxic
nontoxic
toxic
toxic?
toxic
toxic
toxic?
po
1
1
1
1
1
rt
wp
rb
rt
t1
rt;1f
po
po
po
po
po,iv
po
iv
iv;po
po
nontoxic
toxic
alkaloids
+N
-N
toxic
ap
po
toxic
toxic
nontoxic

FAMILY
SCIENTIFIC NAME
ETH
Piperaceae
Piperaceae
Piperaceae
Piperaceae
Pinosporaceae
Plantaginaceae
Piper cubeba
Piper guineense
Piper longum
Piper nigrum
Pittosporum floribundum
Plantago asiatica
1
1
Plantaginaceae
Plantaginaceae
Plantaginaceae
Plantaginaceae
Polemoniaceae
Polygonaceae
Polygonaceae
Polygonaceae
Polygonaceae
Polygonaceae
Polygonaceae
Polygonaceae
Polygonaceae
Polygonaceae
Polygonaceae
Polygonaceae
Polygonaceae
Polygonaceae
Polygonaceae
Polygonaceae
Portulacaceae
Ponulacaceae
Proteaceae
Punicaceae
Plantago himalaica
Plantago lanceolata
Plantago major
Plantago ovata
Loeselia mexicana
Calligonum comosum
Fagopyrum cymosum
Fagopyrum esculentum
Polygonum aviculare
Polygonum bistorta
Polygonum cuspidatum
Polygonum multiflorum
Polygonum reynoutria
Rheum officinale
Rumex acetosa
Rumex ;aponicus
Rumex nepalensis
Rumex nervosus
Rumex patientia
Rumex vesicarius
Portulaca oleracea
Talinum portulacifolium
Grevillea robusta
Punica granatum
Pyrolaceae
Rafflesiaceae
Ranunculaceae
Chimaphila umbellata
Cytinus hypocistis
Aconitum carmichaelii
1
1
1
Ranunculaceae
Ranunculaceae
Ranunculaceae
Ranunculaceae
Ranunculaceae
Ranunculaceae
Ranunculaceae
Ranunculaceae
Aconitum moschatum
Aconitum violaceum
Caltha palustris
Cimicifuga racemosa
Clematis armandii
Clematis barbellata
Clematis montana
Coptis chinensis
1
1
Ranunculaceae
Ranunculaceae
Ranunculaceae
Rhamnaceae
Rhamnaceae
Rhamnaceae
Rhamnaceae
Coptis teeta
Naravelia zeylanica
Nigella sativa
Ceanothus americanus
Colubrina glomerata
Ziziphus ;u;uba
Ziziphus rugosa
Rhamnaceae
Rhizophoraceae
Rhizophoraceae
Rhizophoraceae
Ziziphus vulgaris
Bruguiera conjugata
Ceriops roxburghiana
Ceriops tagal
ACI1VITY
PART
TESTED
ROUTE
ADMIN.
ACI1VE
CONSTIIlJENT
+N
wp
po
-N
+N,-S
ap
sd
po
po
+N
-N
wp
wp
po
+D
+A
+A,N
-N
?N
+N,-A
sd
wp
ap
wp
sd
po
po,ip
po
po
po
plantagomucilage A
+N
?A
+N
?Y
+N
+N
-N
nontoxic
nontoxic
nontoxic
nontoxic?
nontoxic?
rt
wp
If,st
rz
If,st
If
wp
po
po
po
po
po
po
po
+N
+N,?A
sd
sd,wp
po
po
-N
?N
ap
ap,fl
po
po
?N
If
po
+A,Y,N,-S
rt
ip
rt
nontoxic
nontoxic?
nontoxic
nontoxic?
nontoxic
1
1
1
1
-N
+N
wp
po
-N
-N
+A,D,N
ap
ap
rz
po
po
po
+N
-N
+A,-S,N
rz
ap
sd
po
po
po
+N,-A
+N
If
sb
po
+N,?Y,-A
-N
-N
+N
If,fr
ap
ap
sb
po
po
po
po
nontoxic
nontoxic
toxid
nontoxic
nontoxic
aconitans a-d
(A, H, ip)
2
1
1
1
1
toxic
toxic
toxic
toxic
toxic
toxic
toxic
nontoxic
nontoxic
toxic
nontoxic
nontoxic?
nontoxic
nontoxic
3
1
TOXICITY
nontoxic
185
berberine
(A,H,po)
toxic
toxic
nontoxic
alkaloids
flavonoid
glycosides:
quercetin-3-0rhamnoside,
myricetin-3-0rhamnoside
toxic
nontoxic
toxic
nontoxic
toxic
186
FAMILY
SCIENTIFIC NAME
ETH
ACTIVITY
PART
TESTED
ROUTE
ADMIN.
Rhizophoraceae
Rhizophoraceae
Rhizophoraceae
Rhizophoraceae
Rosaceae
Rosaceae
Rosaceae
Rosaceae
Rosaceae
Rosaceae
Rosaceae
Rosaceae
Rosaceae
Kandelia candel
Kandelia rheedii
Rhizophora mangle
Rhizophora mucronata
Agrimonia eupatoria
Alchemilla vulgaris
Crataegus azarolus
Crataegus pubescens
Cydonia oblonga
Eriobotrya japonica
Filipendula ulmaria
Fragaria vesca
Poterium ancistroides
1
1
1
1
2
1
1
1
1
-N
sb
po
Rosaceae
Rosaceae
Rosaceae
Rosaceae
Rosaceae
Rosaceae
Rosaceae
Rosaceae
Rosaceae
Rosaceae
Rosaceae
Rosaceae
Rosaceae
Rosaceae
Rosaceae
Rosaceae
Rosaceae
Rubiaceae
Rubiaceae
Rubiaceae
Rubiaceae
Rubiaceae
Rubiaceae
Rubiaceae
Rubiaceae
Prunus amygdalus
Prunus davidiana
Prunus persica
Pyrus communis
Pyrus malus
Rosa canina
Rosa multiflora
Rosa mgosa
Rosa sericea
Rubus corea nus
Rubus fruticosus
Rubus idaeus
Rubus micropetalus
Rubus nutantiflorus
Rubus paniculatus
Rubus ulmifolius
Sarcopoterium spinosum
Anthocephalus indicus
Borreria verticillata
Canthillm sp.
Cephalanthus glabrata
Cinchona officinalis
Coffea arabica
Coutarea hexandra
Coutarea latif/ora
Rubiaceae
Rubiaceae
Rubiaceae
Rubiaceae
Rubiaceae
Rubiaceae
Rubiaceae
Rubiaceae
Rubiaceae
Rubiaceae
Rubiaceae
Rubiaceae
Rubiaceae
Rubiaceae
Rutaceae
Gardellia ;asminoides
Gardenia taitensis
Hamiltonia suaveolens
Hedyotis biflora
Ixora arborea
Ixora coccinea
Morinda citrifolia
Mussaellda glabra
Oldenlandia biflora
Psychotria dalzellii
Psychotria monticola
Randia dumetorum
Rubia cordifolia
Wendlandia wallichii
Aegle marmelos
Rutaceae
Rutaceae
Rutaceae
Boem/illghausenia albiflora
Casimiroa edulis
Citrus Qllrantiifolia
1
1
4
1
2
1
1
1
1
2
1
1
1
1
1
1
1
TOXICITY
toxic?
+N,-N
+S,-N
-S,N
ap,sb
If
If
po
po
po
nontoxic?
nontoxic?
nontoxic
toxic
?A,N
-S
+A
-S,+G,N
ap
wp
If
ap
po,ip
po
sc
po
+N
+A,S
-N
If
st
ap
ip
po
+D,-N
+N
+S
+N,-S
-N
fr
fr
rt
ap
po
ip
po
+A,G,-S,N
-A,=E,+N
-N
-N
-N
If
If
ap
wp
ap
po
sc
po
po
po
+A,D,N
+N
wp,rb
sb
po
po
+D
sb
po
+N
+N
sb
sd
po
po
quinine
+A,-D,N
wp
po
coutareoside
(hydroxycoum-arin
glucoside) (A, po)
geniposide
+A,E,N
+A
-N
-N
-N
-N
+A
-N
-N
+N
+N
-N
+G,-A,S,?N
rt
ap
ap
ap
ap
ap,fr
wp
ap
wp
fr,sb
ap
ap
fr,lf,rt
po
po
po
po
po
po
po
po
po
po
po
po
po
+N
wp
po
-N
ap
po
nontoxic
tormentic acid (H,
po) inactive A, po
toxic
+G
1
1
ACTIVE
CONSTITIJENT
toxic
nontoxic
nontoxic
nontoxic
toxic
nontoxic
toxic
nontoxic
nontoxic
nontoxic
nontoxic
nontoxic?
toxic
toxic
toxic?
nontoxic
nontoxic?
nontoxic
nontoxic?
nontoxic
nontoxic
nontoxic
?
toxic
toxic
nontoxic
nontoxic
toxic
daucosterol,
lupeol, scopoletin
(A,H,po)
nontoxic
1
diphenylamine?
toxic!
nontoxic
187
FAMILY
SCIENTIFIC NAME
Ern
ACITVITY
PART
TESTED
ROUfE
ADMIN.
ACTIVE
CONSTITIJENT
TOXICITY
Rutaceae
Rutaceae
Rutaceae
Rutaceae
Rutaceae
Rutaceae
Rutaceae
Rutaceae
Rutaceae
Rutaceae
Rutaceae
Sabiaceae
Sabiaceae
Salicaceae
Salicaceae
Salicaceae
Citrus aurantium
Citrus bergamia
Citrus limon
Clausena pentaphylla
Feronia limonia
Moniera trifolia
Murraya koenigii
Phellodendron amurense
Toddalia asiatica
Zanthoxylum alatum
Zanthoxylum ovalifolium
Sabia lanceolata
Sabia limoniacea
Populus tremuloides
Salix nigra
Salix tetrasperma
?Y
fr
po
diphenylamine?
diphenylamine?
diphenylamine?
-N
+N
ap
fr
po
po
nontoxic
nontoxic?
nontoxic
nontoxic
nontoxic
+A,N
+N,?S,G
-N
+N
-N
-N
-N
If
rt,sb
ap
st
ap
ap
ap
po
po
po
po
po
po
po
+N
-N
fl,sb
ap
po
Salvadoraceae
Santalaceae
Sapindaceae
Salvadora persica
Santalum album
Blighia sapida
+G
+N
+E,P,N
rt
wd
fr
po
po
po
Sapindaceae
Sapindaceae
Sapotaceae
Sapotaceae
Sapotaceae
Sapotaceae
Sapotaceae
Saururaceae
Saururaceae
Saxifragaceae
Saxifragaceae
Saxifragaceae
Saxifragaceae
Saxifragaceae
Saxifragaceae
Dodonaea viscosa
Sap indus laurifolius
Bumelia sartorum
1
Lucuma lucentifo/ia
1
Madhuca longifolia
1
Mimusops elengi
1
Pouteria tomentosa
Anemopsis califomica
1
Houttuynia cordata
Bergenia stracheyi
Chrysosplenium trichospermum
Heuchera americana
1
Hydrangea altissima
Hydrangea arborescens
1
Hydrangea paniculata
+N
-N
+A.N,-E
wp
ap
rb
po
po
-N
sb
po
+N
wp
po
+A
+N
wp
rt
-N
ip
po
wp
-N
ap
po
+N
mu,sb
po
Schisandraceae
Scrophulariaceae
Scrophulariaceae
Scrophulariaceae
Scrophulariaceae
Scrophulariaceae
Scrophulariaceae
Scrophulariaceae
Scrophulariaceae
Scrophulariaceae
Scrophulariaceae
Scrophulariaceae
Scrophulariaceae
Scrophulariaceae
Scrophulariaceae
Schisandra chinensis
Angelonia grandi{lora
Angelonia salicariaefolia
Anticharis arabica
Antirrhinum glaucum
Capraria bi{lora
Cymbalaria muralis
Hemiphragma heterophyllum
lsoplexis canariensis
lsoplexis isabelliana
Kickxia ramosissima
Leucophyllum texanum
Mazus surculosus
Pedicularis rhinanthoides
Rehmannia glutinosa
+U,:A,-S
-N
-N
fr
wp
ap
po
po
po
+A
-N
-N
If
wp
wp
po,ip
po
po
nontoxic
-N
wp
po
nontoxic
wp
wp
Scrophulariaceae
Scrophulariaceae
Scrophulariaceae
Scrophulariaceae
Scrophulariaceae
Scrophulariaceae
Scrophulariaceae
Scrophulariaceae
Rehmannia lutea
Scoparia dulcis
Scrophularia aquatica
Scrophularia buergeriana
Scrophularia glabrata
Scrophztlaria ningpoensis
Scrophularia nodosa
Striga gesneroides
+N
+N
+D.N,?Y,
A,G.-S
+N
+A.?D,N
1
1
1
1
1
1
nontoxic
toxic
toxic
nontoxic
toxic
nontoxic
nontoxic?
?
salicylic acid
(A,H,po)
nontoxic
nontoxic
hypoglycins a
and b (H, po)
toxic
toxic
nontoxic
po
paniculatan
mucilage
1
1
3
1
toxic
nontoxic
nontoxic
toxic
toxic
toxid
nontoxic
nontoxic
nontoxic
nontoxic
nontoxic
toxic
1
1
1
1
3
1
3
2
1
1
1
rt
po
rt
wp
po
po
nontoxic?
nontoxic
nontoxic?
?
toxic
toxic?
?A
rt
po
-N
wp
po
2
1
iridoid glycoside
rehmannioside D
rehmanin
188
FAMILY
SCIENTIFIC NAME
ETH
Scrophulariaceae
Simaroubaceae
Simaroubaceae
Simaroubaceae
Simaroubaceae
Solanaceae
Solanaceae
Solanaceae
Torenia asiatica
Ailanthus altissima
Ailanthus excelsa
Brucea mollis
Quassia amara
Atropa belladonna
Capsicum annuum
Capsicum {rutescens
Solanaceae
Solanaceae
Solanaceae
Solanaceae
Cestrum nocturnum
Datura quercifolia
Hyoscyamus niger
Lycium barbatum
Solanaceae
Lycium chinense
Solanaceae
Lycopersicum esculentum
Solanaceae
Solanaceae
Solanaceae
Solanaceae
Solanaceae
Solanaceae
Solanaceae
Solanaceae
Solanaceae
Solanaceae
Solanaceae
Nicotiana tabacum
Physalis angulata
Physalis ixocarpa
Physalis peruviana
Solanum argillicolum
Solanum indicum
Solanum nigrum
Solanum sanitwongsei
Solanum torvum
Solanum trilobatum
Solanum tuberosum
Solanaceae
Solanaceae
Stachyuraceae
Sterculiaceae
Sterculiaceae
Sterculiaceae
Sterculiaceae
Sterculiaceae
Styraceae
Withania coagulens
Withania somnifera
Stachyurus himalaicus
Abroma augusta
Eriolaena quinquelocularis
Helicteres isora
Heritiera minor
Pterospermum acerifolium
Styrax benzoin
Symplocaceae
Symplocaceae
Symplocaceae
Tamaricaceae
Theaceae
Symplocos gardneriana
Symplocos racemosa
Symplocos theaefolia
Tamarix canariensis
Camellia sinensis
Theaceae
Tiliaceae
Tiliaceae
Tiliaceae
Tiliaceae
Tiliaceae
Turneraceae
Ulmaceae
Ulmaceae
Urricaceae
Gordonia obtusa
Corchorus olitorius
Grewia asiatica
Grewia hirsuta
Grewia se"ulata
Grewia tiliaefolia
Turnera diffusa
Trema guineensis
Trema orientalis
Urtica dioica
ACTIVITY
PART
TESTED
ROUTE
ADMIN.
-N
-N
-N
ap
sb
ap
po
po
po
+N
+N
?N
If
fr
ap,sd
po
po,ip
po
-N
+N
ap
wp
po
po
+N,-S
fr
po
+N,?A,-S
fr, rb
po
-N
wp
po
+N
fr
po
+N
-N
+N
+N
fr
fr
fr
tb
po
po
po
po
wp
po
po
toxic
po
po
po
nontoxic
toxic
nontoxic
ACTIVE
CONSTlTIJENT
capsaicin
+N
+N
1
1
1
1
1
1
+D
+D,-N
+N
-N
-N
-N
+N
-N
+N
wp
ap
sd,sb
ap
If
IS
po
ip
-N
-N
+N
ap
ap
If
po
po
po
+S,A,N
If
po
-N
+N
+A,P
-N
-N
-N
+A
-N
-N
+E,G,-N,S
ap
If
If,sb
ap
ap
ap,sb
wp
If
ap
wp
po
po
po
po
po
po
po,ip
po
po
po
toxic
toxic
toxic
toxic
toxic
nontoxic
toxid
nontoxic
toxic
toxic
toxic
guanidine
derivatives and
flavonoids
lupeol, scopoletin nontoxic
(A, po)
toxid
nontoxic
toxic
toxic?
toxic
toxic?
1
1
1
2
1
TOXICITY
lupeol (A, po)

lupeol (A, po)
lupeol (A, po)
lupeol (A, po)
lupeol (A, po);
dietary effect
sumaresinoleic
acid
toxic
nontoxic
toxic?
toxic?
nontoxic
nontoxic
toxic
nontoxic
nontoxic
nontoxic
theophylline,
diphenylamine,
epicatechin,
epigallocatechin,
gallocatechine,
caffeine
nontoxic
toxic
nontoxic
toxic
toxic
toxic
nontoxic
nontoxic

FAMILY
SCIENTIRC NAME
Urticaceae
Valerianaceae
Valerianaceae
Valerianaceae
Valerianaceae
Valerianaceae
Valerianaceae
Verbenaceae
Verbenaceae
Verbenaceae
Verbenaceae
Verbenaceae
Verbenaceae
Verbenaceae
Verbenaceae
Urtica urens
Nardostachys jatamansi
Valeriana edulis
Valeriana mexicana
Valeriana officinalis
Valeriana procera
Valeriana sorbifolia
Citharexylum subserratum
Clerodendrum infortunatum
Clerodendrum phlomoides
Clerodendrum serratum
Gmelina arborea
Holmskioldia sanguinea
Lippia graveolens
Premna integrifolia
Verbenaceae
Verbenaceae
Verbenaceae
Verbenaceae
Verbenaceae
Verbenaceae
Violaceae
Vitaceae
Vitaceae
Z ygophyllaceae
Z ygophyllaceae
Zygophyllaceae
Zygophyllaceae
Zygophyllaceae
Zygophyllaceae
Premna latifolia
Premna obtusifolia
Tectona grandis
Verbena bonariensis
Verbena officinalis
Vitex trifolia
Viola canescens
Cissus repens
Vitis bracteolata
Balanites aegyptiaca
Guaiacum officinale
Larrea tridentata
Peganum harmala
Zygophyllum coccineum
Zygophyllum cornutum
Ern
ACTIVITY
PART
TESTED
ROUTE
ADMIN.
+N
1
1
1
2
1
1
1
1
1
1
1
1
1
+A
rt
po,ip
+A
rt
po,ip
+A
-N
+N
+A,D,E,N
-N
+N
-N
rt
ap
wp
wp
wp
st
ap
po,ip
po
po
po
po
po
po
+N
rt,sb
po
+N
+N
?N
+N
-N
-N
-N
-N
-N
+S
sb
st,rt
po
If
po,iv
po
po
po
po
po
po
po
wp
wp
ap
wp
wp
ap
fr
ACTIVE
CONS1TI1JENT
189
TOXICITY
nontoxic?
nontoxic
?
nontoxic
?
nontoxic
nontoxic
nontoxic
toxic
nontoxic
toxid
nontoxic
nontoxic
nontoxic
nontoxic
?
nontoxic
nontoxic?
nontoxic
toxic
toxic
+A,S,-G
sd
po
-A,+G,?N
If
po
toxic
nontoxic
nontoxic?

Marles &amp; Farnsworth 1995 Antidiabetic Plants

Загружено:

Сведения о документе

Авторское право

Доступные форматы

Поделиться этим документом

Поделиться или встроить документ

Параметры публикации

Этот документ был вам полезен?

Это неприемлемый материал?

Авторское право:

Доступные форматы

Marles &amp; Farnsworth 1995 Antidiabetic Plants

Загружено:

Авторское право:

Доступные форматы

Phytomedicine Vol. 2 (2), pp.

1995 by Gustav Fischer Verlag, Stuttgart Jena . New York

Antidiabetic plants and their active constituents1

At least 30 million people throughout the world suffer

pact of the disease is enotmous. In 1987 an estimated 5.7

R. J. Maries and N. R. Farnsworth

as of developing countries still rely on traditional medicines

Background: Diabetes Classification

Diabetes mellitus comprises a group of etiologically and

responsiveness to glucose, and increased glucagon secretion

Antidiabetic plants and their active constituents

le-cys - ser-leu- tyr"gln-Leu-glu-asn-tyr-cys-asn

Boyine insul in:

Fig. 1. Insulin and some synthetic oral hypoglycemic drugs.

couples to cytosolic receptor substrates which can affect

R. J. Marles and N. R. Farnsworth

adult pancreas transplantation (Hellerstrom et al. 1988).

effects of gliclazide beneficial for the prevention of diabetic

Antidiabetic plants and their active cQnstituents

Plants and the Treatment of Diabetes Mellitus

Table 1. Plant Families Most Often Cited for Antidiabetic Activity.

"According to Thorne (1981).

R.]. Marles and N. R. Farnsworth

Table 3. Most Widely Used Traditional Antidiabetic Plants.

Countries where used traditionally

Ecuador, Colombia, Mexico, Venezuela, Jamaica, Madagascar, India, Thailand, England

India, Pakistan, Thailand, West Indies, USA, Portugal

Canary Islands, India, Israel, Portugal, Morocco

Haiti, India, Tunisia, Kuwait, Saudi Arabia

India, Mexico, Guatemala, Virgin Islands, Cuba

England, USA, Guatemala, Nepal, India

Europe, Costa Rica, Mexico, USA

India, Ethiopia, Indonesia, South America (country not specified)

India, Nepal, Tibet, Pakistan

India, Fiji, Saudi Arabia, Trinidad

India, USSR, China, Peru

Spain, Greece, Syria, Israel

India, China, England, USA

such useful drugs as reserpine, from Rauvolfia serpentina,

Antidiabetic plants and their active constituents

Fig. 2. Plant growth regulators with hypoglycemic activity.

man and Zaman 1989, Ivorra et al. 1989, Winkelman

Hypoglycemic Constituents and

R. J. Maries and N. R. Farnsworth

Table 4. Hypoglycemic Natural Products

Pep tides and amines

or counteracting constituents. Some examples of plants

The most widely used traditional remedy for diabetes

Antidiabetic plants and their active constituents

vate ratio, and an increase in ATP contents and energy

R. J. Maries and N. R. Farnsworth

Fig. 4. Hypoglycemic alkaloids of Catharanthus roseus.

Antidiabetic plants and their active constituents

mineral whose salts have insulin-like properties in animal

(CH 3hN+CH 2 CH(NHCOCH 3)CH 2 COO-

Amino Acids from Blighia

Guanidines from Galega

(CH 3hN'CH 2CH(NH 2)CH 2COO-

nase and cytochrome oxidase, thus increasing anaerobic

Vitamins, Coumarins, and Steroids from Trigonella

R.]. Marles and N. R. Farnsworth

Fig. 7. Comparison of the structures of galegine and metformin.

Seeds of a number of other members of the Fabaceae are

Fig. 8. Some antidiabetic constituents of Trigonella foenum-graecum.

Marles & Farnsworth 1995 Antidiabetic Plants

Marles & Farnsworth 1995 Antidiabetic Plants