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doi: 10.1111/j.1468-2494.2011.00647.x
Review Article
Synopsis
Acne vulgaris suppresses an individuals self-confidence by causing
distress with regard to physical appearance, which affects a significant number of individuals during puberty and is delineated by
adolescence. Several treatments have been introduced to decrease
the aesthetic and psychological problems caused by acne. The topical application of therapeutic agents has been found to be more
feasible than hormonal treatment and laser therapy. The ingredients in topical acne treatments, particularly herbs and naturally
derived compounds, have received considerable interest as they
have fewer adverse effects than synthetic agents.
sume
Re
Lacne vulgaire touche a` lassurance dun individu en causant une
detresse face a` son apparence physique. Elle affecte un nombre
important dindividus pendant la puberte et est associee a` ladolescence. Plusieurs traitements ont ete proposes pour diminuer les
proble`mes esthetiques et psychologiques causes par lacne. Lapplication topique dagents therapeutiques a ete estimee plus aisee
quun traitement hormonal et une therapie laser. Les ingredients
des traitements topiques de lacne, particulie`rement les plantes et
les composes naturels derives ont suscite un interet considerable
par leurs moindres effets indesirables que les ingredients synthetiques.
Introduction
Acne is a skin disorder that suppresses an individuals self-esteem
with regard to physical appearance and has a clinical onset during
puberty and adolescence [1]. A high incidence of acne is found in
girls aged 1417 and in boys aged 1619 [2]. The pathogenesis of
acne is regulated by sebum hypersecretion in deformed follicles,
which leads to microcomedones, and the follicular hyperproliferation of microcomedones causes inflammation [3], and comedones
[4] in both open and closed types (black and white comedones)
appearing in papules, pustules, nodules and cysts [5]. The resulting
skin condition with sebum enrichment is prone to the anaerobic
growth of Propionibacterium acnes, which is the main causative
Correspondence: Nattaya Lourith, School of Cosmetic Science, Mae Fah
Luang University, Chiang Rai 57100, Thailand. Tel.: +66 53 916834;
fax: +66 53 916831; e-mail: nattayal@mfu.ac.th
289
keratinocytes and sebocytes and neutrophil function [18]. Colonization of this anaerobe consequently produces cytokines and other
proinflammatory compounds including interleukins (IL), tumour
necrosis factors (TNF), interferon (IFN) gamma and granulocyte
macrophage colony-stimulating factor (GM-CSF) [5, 19]. In
addition to follicular keratinocytes, IL induction leads to microcomedone formation, and the bacterium activates TLRs inducing
the attraction of lymphocytes, neutrophils and macrophages.
Abnormal keratinization and deficiency of linoleic acid in the
follicle also promote the growth of P. acne [20], which in turn stimulates the production of proinflammatory cytokines/chemokines in
sebocytes [21] and provokes chronic inflammatory lesions [22].
Reactive oxygen species in acne formation
Reactive oxygen species (ROS) are subsequently generated from the
hypercolonization of P. acnes [5, 23] in addition to metabolism in
living organisms and from UV exposure. Although ROS perform a
useful function in the skin barrier against acne microbes [24, 25],
excess formation affects skin condition by activating neutrophil
infiltration. ROS including singlet oxygen, superoxide anion, hydroxyl radical, hydrogen peroxide, lipid peroxide and nitric oxide (NO)
play an important role in inflammatory acne as well as in tissue
injury. ROS stimulate the formation of nuclear factor jB (NF-jB)
[26], promote TNF formation [27] and consequently activate T
lymphocytes and keratinocytes. The cytokines IL, TNF, IFN, lipopolysaccharide (LPS), transforming growth factor (TGF) and prostaglandin (PG) are then produced and released [2832].
In summary, skin inflammation is initiated by CD4+ in T lymphocytes, regulated by TLRs following neutrophil infiltration which
generates ROS, and protease enzymes leading to follicular wall
rupture of sebaceous glands. This consequently changes the composition of sebum, particularly linoleic acid. Hyperkeratinization is
initiated as well as a reduction in desquamation. Subsequently, the
proinflammatory cytokines, NF-jB, IL, TNF, IFN, LPS, TGF, PG and
GM-CSF are released causing microcomedones. The resulting microcomedones further develop into comedones and inflammatory
lesions.
The topical agents used in the treatment of acne have been summarized, particularly the naturally derived compounds as they are
believed to be safer than the synthetic compounds [33]. In addition, P. acne resistance to some antibiotics used in the treatment of
acne has been observed [34, 35].
Active ingredients for topical acne treatment
Retinoic acid and derivatives
Keratolytic agents such as cis-retinoic acid, retinol and retinol
ester are commonly used to normalize keratinization as they have
a suppressive effect on sebaceous gland function [9, 36, 37].
These vitamin A derivatives suppress TLRs expression and inhibit
IL and IFN production. Cell migration of CD4+ and CD8+ T lymphocytes and macrophage is inhibited [38, 39]. Tretinoin or
trans-retinoic acid is also used as a comedolytic agent. It normalizes follicular epithelium desquamation by unplugging the follicle.
The growth of P. acnes is reduced consequently. However, topical
application of anti-inflammatory retinoids [40] leads to irritation,
which is dose responsive [41]. Therefore, appropriate vehicles
should be used to diminish this effect in addition to structural
modification. Adapalene, a retinoid-like activity agent, with
comedolytic and anti-inflammatory effects was synthesized. It has
Vitamin C
Macrolides
In addition to the aforementioned active agents, topical administration of antibiotics particularly macrolides are used in the treatment
of acne. Oral administration is used for severe acne and acne that
is resistant to topical treatment [1]. The macrolides, erythromycin
and clindamycin, are used with respect to their anti-oxidant and
anti-inflammatory activities [69, 70]. However, P. acne resistance
[35] as well as gastrointestinal irritation and vaginal candidiasis
especially photosensitivity including drug interactions were found
following applications of macrolides [66]. Although a structural
modification in a fewer gastrointestinal side-effect agent, azithromycin, was carried out. It was found to accumulate in breast milk
[71].
Tetracyclines
Another class of antibiotic that is widely used in acne treatment is
tetracyclines. Tetracyclines show anti-inflammatory activity inhibiting PG synthesis as well as NO synthase suppression [72, 73].
However, the adverse effects of tetracyclines are similar to those of
macrolides. The most common side effects are lightheadedness,
dizziness and tinnitus [74] including yellow staining of teeth and
nail diseases such as photo-onycholysis, although these side effects
are not common in doxycycline and minocycline. Light sensitivity
has been demonstrated following the administration of doxycycline
[75].
To overcome the adverse effects of antibiotics, combination therapy with a systemic treatment should be conducted. Stepwise treatment must be carried out to minimize antibiotic exposure
diminishing microbial resistance.
In addition to the aforementioned treatments, hormonal therapy
with anti-androgens such as spironolactone, flutamine and cyproterone acetate has been used to treat acne. However, adverse
effects have been noted [10, 76]. Laser and light-based therapy
potentially clear acne with improvements in acne scarring and skin
texture. Nonetheless, these methods are costly and pain causing
[77].
Thus, a natural therapy lacking adverse effects is highly desired
with respect to its conceivable safety [33] and rare P. acne resistance. Naturally derived compounds, particularly those from herbs,
are therefore reviewed in this article. The herbs included are those
of well known and candidate herbs used in the future development
of anti-acne products.
291
Function
Application/Dosage
Abies koreana
Allium cepa
Aloe vera
Anthemis aciphylla
Anthemis nobilis
Aralia continentalis
Azadirachta indica
Centella asiatica
Clerodendron trichotomum
Curcuma longa
Garcinia mangostana
Glycyrrhiza glabra
Gossypium barbadense
Eucommia ulmoides
Hemidesmus incidus
Humulus lupus
Magnolia officinalis
Matricaria recutita
Melaleuca alternifolia
Ocimum gratissimum
Phyllanthus emblica
Punica granatum
Rosa damascene
Salvia sclarea
Selginella involvens
Tamarix bovena
Trifolium pretense
Ziziphora clinopodioides
Essential oil
Poultice
Cream, gel
Essential oil
Cream, ointment
Not available
Cream, gel, essential oil
Tonic
Not available
Cream, gel
Not available
Not available
Decoction
Tonic
Cream, gel
Not available
Decoction
Cream, ointment
Cream, gel, essential oil
Gel
Not available
Not available
Tea
Essential oil
Not available
Essential oil
Lotion
Essential oil
Herbs
Salicylic acid
Azelaic acid
superoxide assays [115]. Its anti-oxidant quality was high highlighting its capacity in the development of acne care products that
have already been commercialized in Asia.
The inhibition of NO production and scavenging activity of Selginella involvens were found to be dose dependent. This herb also has
an anti-inflammatory effect towards IL in keratinocytes. Furthermore, its non-antibiotic, anti-microbial potential on P. acnes has
been reported and was non-cytotoxic at a concentration
<50 lg ml)1 [116].
There were anti-inflammatory reports of Chinese medicinal
plants root and leaf extracts. These include Aralia continentalis via
inhibition of cyclooxygenase-2 (COX-2) and NO expression including NF-jB deactivation [117]. Clerodendron trichotomum was found
to suppress PGE2 production [118], which appropriates for inflammatory acne treatment.
Prevention of acne was traditionally carried out using Ayurvedic
formulations containing Curcuma longa [80, 119], which have antibacterial and anti-inflammatory activities [120]. This plant has
long been used in Thai folk remedies for skin care and for its aromatherapy aspects in various traditional preparations, for instance
masks, and compresses.
Garcinia mangostana is another economic fruit of Thailand. Its
pericarp consisted of xanthones that potently inhibit P. acnes and
S. epidermidis [121]. These anti-bacterial activities were found
increased in a mature fruit [122]. Furthermore, it was found to be
highly effective in free radical scavenging following P. acnes induction and suppressed the production of TNF-a, a pro-inflammatory
cytokine [123], particularly in young fruit [122].
The anti-inflammatory effects of free fatty acid in sebum particularly linoleic and lauric acids were found to inhibit P. acnes [124].
Therefore, plants containing linoleic acid may be applicable in acne
lesion reduction. Sunflower (Helianthus annuus) and pumpkin
(Cucurbita pepo) seed oils as well as flax or linseed oil (Linum sp.),
which have a high fatty acid content mainly linoleic and linolenic
acids, were incorporated into a preparation for dermatological
treatments including acne [125]. In addition to those natural oils,
apricot (Prunus armeniaca), argan (Argania spinosa), avocado (Persea
gratissima), baobab (Adansonia digitata), black currant seed (Rines
nigrum), borage seed (Borago officinalis), cranberry seed (Vaccinium
macrocarpon), corn (Zea mays), cotton seed (Gossypium sp.), evening
primrose (Oenothera biennis), grape seed (Vitis vinifera), hazelnut
(Corylus americana), manketti nut (Schinziophyton rautanenii), moringa (Moringa oliefera), palm (Elaesis guineensisi), poppy seed (Papaver
orientale), rapeseed (Brassica napus), raspberry seed (Rubus idaeus),
293
Conclusion
The herbs summarized in Tables I and II were found to effectively
reduce inflammatory acne lesions through mechanisms related to
sebaceous glands, P. acnes and ROS. However, an appropriate delivery system should be developed to impart their efficacies in addition
to the standardization of these herbs. Furthermore, an optimized and
effective dose should be evaluated prior to the development of
preparations in order to avoid irritation or allergy in subjects with
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