3.3. Medicinal Plants with Anti-Acne Activity
Herbal medicines are gaining increased popularity due to their advantages, such as better patient tolerance, long history of use, fewer side-effects and being relatively less expensive (8). Furthermore, they have provided good evidence for the treatment of a wide variety of difficult to cure diseases (7, 32-41). These plants are used alone or in combination with synthetic drugs to treat diseases (42-47). More importantly, other than consumption as preventive or treatment remedy, they might be accompanied with synthetic drugs to reduce their side effects (7, 47-54). With no exception, botanical drugs are also used accompanied by other methods or alone to treat acne vulgaris. Many medicinal plants with anti-inflammation and antibacterial activities are used in different ways in the treatment of acne and other infective diseases (54-60).
Matricaria recutita, Calendula officinalis and Triticum aestivum are commonly used species of these plants (61). Creams or aqueous infusions made from plants including astringents and composites such as tannins are used topically on skin after cleansing or a steam bath. Hamamelis virginiana has tannins and extraction of epidermis is commonly used to treat acne because it is very safe for topical prescription. Other plants containing tannins are white oak's bark (Quercus alba), walnut's leaf (Juglans regia), Agrimonia eupatoria, Syzygium cuminum, Ledum latifolium, Alchemilla mollis, Lavandula angustifolia, Verbascum thapsus, Krameria triandra, Rheum palmatum, Hypericum perforatum and Rumex crispus (62). Other plants that are traditionally used topically or as a depurative include Bellis perennis, Viola tricolor, Elymus repens and Taraxacum officinale. Topical use of horsetail depurative (Equisetum species) is recommended due to the high amount of silicic acid and yellow milk of Aloe ferox fresh leaves because of anthranoids (61).
Vitex agnus-castus is used for acne before menstruation. The whole fruit extract acting on follicle stimulating and luteinizing hormone levels in the pituitary gland led to an increase in progesterone and decrease in estrogen levels through the dopaminergic mechanism, declining the level of premenstrual prolactin. German Commission E has recommended daily intake of 40 mg Vitex agnus-castus extract for the treatment of acne. Pregnant and nursing women should not use this plant. Adverse side effects such as gastrointestinal disturbances and skin rashes have been reported (63, 64). In addition to the traditional use of herbal medicines as anti-acne, antibacterial activities of some plants in order to determine their potential as acne herbal treatment have been investigated (65). An anaerobic pathogen, P. acnes, plays an important role in acne pathogenesis and seems to begin the inflammatory process through stimulating the production of reactive oxygen species (ROS) and release of inflammatory and proinflammatory cytokines (66). Interestingly, the inhibitory effect of licorice (Glycyrrhiza glabra) is not associated with bacterial resistance induction of the growth of P. acnes in vitro (67).
Screening of plant extracts for anti-bacterial and yeast activity has shown that usnic acid, an effective substance of Usnea barbata, has strong inhibition effect on the growth of P. acnes. The growth of bacteria was inhibited at ≥ 1μg/mL concentrations. In addition, U. barbata was found to have a wide range of anti-oxidative and antibacterial properties suggesting that it may be a promising substance in acne treatment (68). A four-week clinical trial compared the essence of Ocimum gratissimum at four different levels (0.5-5%) and four different bases by placebo and standard treatment (benzoyl peroxide, 10%). Two percent essence of O. gratissimum in a hydrophilic base (alcohol or cetomacrogol) reduced skin lesions faster than standard therapy, without any side effects, while 5% concentration was effective but with skin irritation (65). A study reported that topical application of O. gratissimum essence was superior to placebo and clindamycin 1%. In this study, topical yellow Aloe vera was not solely effective in acne treatment, however, showed a synergistic interaction with O. gratissimum (69).
Topical use of 50% Aloe vera gel with tretinoin cream was well tolerated during eight weeks in a randomized double-blind clinical trial with 60 patients suffering from mild-moderate acne and was significantly more effective than tretinoin and vehicle (70). German Commission E has confirmed the topical use of Solanum dulcamara and edible use of Saccharomyces cerevisiae because of their antibacterial effect as an acne remedy (71). In China, Lemna minor has been used topically to treat acne. A clinical trial noted that consumption of gugulipid, standardized extraction of oleoresin of an Indian herbal plant named Commiphora mukul, for three months, was effective in treating acne. Interestingly, the patients with oily skin respond remarkably to gugulipid. It should be noted that the aforementioned studies had a number of methodological limitations, for instance, there were only 10 individuals in each group (and without placebo), thus there was not enough power to determine significant differences between the medicines (63).
Use of 2% lotion of green tea (Camellia sinensis) topically, during six weeks among 20 patients suffering from mild to moderate acne, was found to be effective compared with pretreatment. Tannins and flavonoids of green tea may possess an anti-acne effect, since they seem to have an antiseptic effect while tannins also have an anti-inflammatory effect (71). In Western traditional medicine the root of Mahonia aquifolium or Berberis aquifolium has been used to treat chronic skin rashes (pustule). The main effective substances of Mahonia extracts include two alkaloids of Protoberberine, namely Jatrorrhizine and Berberine, which have inhibited the in vitro growth of Staphylococcus coagulase, P. acne and Candida species. Berberine (100 μmol/mL) in an animal model inhibited fat production in Sebaceous by 63% (72).
Berberine alkaloid is a bitter substance with anti-fat production and anti-inflammatory effect on 3T3-L1 fatty cells, and its anti-fat production effect, has been related to down regulation of fat production enzymes and transcription factors. However, the exact mechanism of Berberine and herbs enriched in Berberine is still unknown (73). Tea tree oil (TTO) has a broad spectrum of antibacterial properties and reduces skin inflammation due to inhibition of histamine release. Five percent tea tree oil and 5% benzoyl peroxide improved acne in a three-month single-blind clinical trial on 124 patients, however, the effect of tea tree oil began slowly and a few patients in the tea tree oil group showed skin complications (74). While the mentioned study had no placebo group, a 45-day double-blind, randomized trial with 60 patients showed the efficacy of 5% topical gel of tea tree oil on mild to moderate vulgaris acne. The efficiency of tea tree oil gel for the total numbers of acne lesions and intensity index of acne was found to be 3.55 and 5.75 times higher than the placebo, respectively (75).
Gluconolactone is made of a polyhydroxy acid formed by S. boulardii. The results of a double-blind clinical study on 150 patients with topical usage of a 14% gluconolactone solution showed the removal of inflamed acne lesions, which was significantly superior when compared to the placebo and comparable with 5% benzoyl peroxide, however, with less adverse side effects (76). The plants, which have gained more popularity for the treatment or prevention of Acne vulgaris during the past two decades, are presented with more details below.