A Review on the Role of Medicinal Plants in Treatment of Acne View PDF

The skin is the outermost layer of the body that is often easily damaged by environmental factors as well as stress and poor eating habits. Acne (known also as Acne Vulgaris) is an inflammatory disorder of the pilosebaceous unit, which runs a chronic course and it is self-limiting. Acne vulgaris is triggered by Cutibacterium acnes in adolescence, under the influence of normal circulating dehydroepiandrosterone (DHEA). It is a very common skin disorder which can present with inflammatory and non-inflammatory lesions chiefly on the face but can also occur on the upper arms, trunk, and back [1,2]. Acne can persist into adulthood, with a 50.9% prevalence rate of acne in women ages 20 to 29 years versus 26.3% in women ages 40 to 49 years [3]. Female patients account for two thirds of visits made to dermatologists for acne, and one third of all dermatology office visits for acne are by women who are older than 25 years [4]. The main types of acne scars include icepick, rolling, and boxcar [5,6].

In a nutshell, four key pathogenic processes lead to the formation of acne lesions: alteration of follicular keratinization that leads to comedones; increased and altered sebum production under androgen control; follicular colonization by Propionibacterium acnes; and complex inflammatory mechanisms that involve both innate and acquired immunity [7]. Propionibacterium acnes has been identified as the causative microorganism involved in the progression of acne vulgaris. It is a Gram-positive, aero tolerant anaerobic bacillus with the ability to produce propionic acid as a metabolic by-product. This microorganism forms part of the normal skin microflora and remains on the skin from birth until death. In 1963, P. acnes was injected into sterile cysts of steatocystomas (noncancerous cysts originating in the sebaceous glands), resulting in subsequent inflammation, providing evidence that this microorganism is involved in inflammatory acne [8]. In doing so, many studies have been conducted to find more causes for appearance of acne. However, Lajevardi V, et al. [9], for example, found no statistically significant difference in BMI among people with different severities of acne.

Accordingly, acne leads to significant morbidity that is associated with residual scarring and psychological disturbances such as poor self-image, depression, and anxiety, which leads to a negative impact on quality of life [10]. Inflammation is one of the major symptoms of acne, resulting in the formation of pustules, papules and cysts. In more severe cases of inflammatory acne, the formation of cysts is often accompanied with the formation of scars. This has a significant impact on psychosocial attributes, especially in teenagers who are commonly afflicted with acne. Increased efficiency could potentially be accompanied by reduced development of resistant strains of P. acnes. Besides, acne affects the pilosebaceous follicle, a structure comprised of the hair follicle and its associated sebaceous gland. The exact sequence and nature of these factors are not yet known, but there is a general agreement that acne vulgaris is a multifactorial disease. The etiology of acne is hypothesized to occur in four main steps, namely increased levels of sebum secretion, hyper cornification (blockage and hardening) of the follicular duct, proliferation of P. acnes, and inflammation (Figure 1) [11].

Therefore, treatment of acne is of a high importance and acne vulgaris and the acne-causing bacterium, P. acnes, have been intensively studied and several solutions have been proposed. For instance, in a comparison between metformin and isotretinoin, Behrangi E, et al. (2019) report that metformin is effective in treating late-onset or resistant acne and improving metabolic status, without serious side effects [12]. In patients with altered metabolic profiles such as polycystic ovary syndrome (PCOS), metformin seems to be superior to isotretinoin regarding acne treatment. In another comparative study between the therapeutic effect of micro needling versus tretinoin in patients with comedonal acne, micro needling seems to be a more effective, permanent and satisfactory treatment in the treatment of comedonal acne [13]. In addition, Montelukast has been found to be an effective and safe medication for moderate-level acne treatment [14]. On the other hand, nonmedical device-based therapies are reported to largely improve the treatment of active inflammatory acne vulgaris, especially in patients who are not compliant or eligible to consume acne medications, do not respond to these drugs over a specified period of time, or do not sustain in the remission phase [15]. Accordingly, significant advancements have been seen in scare related acne treatment in the recent decade, including novel skin substitutes, pharmacological interventions, advanced surgical approaches such as laser therapy, fat grafting and skin grafting, cosmetic filler and pharmacological method [5]. Furthermore, several studies have been undertaken on the association of acne with diet and serum levels of micronutrients and vitamins, including calcium, vitamin D and zinc, and new treatments such as probiotics [16-19]. However, little research has focused on the use of medicine.

The present study is actually a qualitative work and a careful review and critical analysis of the medical literature. We undertook several searches in such authoritative online databases as Pubmed, MEDLINE, Link of Springer, Online Library of Wiley, Science Direct of Elsevier, Cambridge Core, and Cochrane. To this end, the special keywords (i.e. medicinal plants, acne, Acne Vulgaris, herbs, treatment, and herbal medicine) associated with the subject of this review were determined, based on which the searches were conducted. The time range of the investigated content is limited from 2000 to 2019.

The conventional medicinal plants and plant compounds for treatment of acne

First of all, we will represent the medicinal plants which have been reported by authors to be effective on treatment of acne. Accordingly, medicinal plants have the potential to be commercialized not only for their ability to act as antimicrobial agents but also for the treatment of symptoms associated with acne vulgaris. The species with potential commercial value have been summarized in table 1, which includes the traditional use and the biological activity that may support their use.

Table 1: Medicinal plants with traditional usage and biological activity for the treatment of acne vulgaris and its symptoms.

In addition, although plants contain many constituents, the isolation of pure compounds from plants is an important part of the drug discovery process. The isolation of compounds known to be responsible for biological activity may not only enhance both the isolation process and the effectiveness but also provide valuable information of the mechanism of action. Table 2 summarizes some isolated plant compounds that show activity against P. acnes and acne symptoms.

Table 2. Plant compounds reported to have anti-acne activity.

In addition to above mentioned plants, Leucosidea sericea Eckl and Zeyh is pointed which is a plant belonging to the Rosaceae family and indigenous to South Africa. It is found in the Eastern Cape, Free State, and KwaZulu-Natal provinces. It is traditionally used against various ailments including severe inflammation of the eye. In combination with other plants, this species is used as an astringent. Astringents are generally prescribed for patients who suffer from very oily skin [46]. L. sericea is one of the few plants that has passed through extensive research and development in terms of antiacne activity. The research performed at the University of Pretoria, Department of Plant Science has led to the filing of an international (PCT-Patent Cooperation Treaty) patent. L. sericea was investigated in a full clinical study on human volunteers. Volunteers of two different skin types were used, Fitzpatrick skin type IV and V. The Fitzpatrick skin type system was developed by dermatologist, Thomas B Fitzpatrick in 1975, as a classification system for skin types that react differently to Ultraviolet light. Type IV is characterized as a moderate brown, typically Mediterranean, which rarely burns and tans well. Type V is characterized as dark brown, typically Middle Eastern, which very rarely burns and tans well. These skin types are more prone to visible scarring and postinflammatory hyperpigmentation caused by acne lesions. In their study, use of Leucosidea sericea was effective in reduction of comedones, papules, pustules and whiteheads compared to placebo control [47].

In another study on antibacterial and antioxidant strategies for acne treatment through plant extracts in Indian society, Vora J, et al. (2019) [48] revealed that different plant extracts showed noticeable activity against different test organisms. The plant extracts of R. officinalis, M. Chamomilla and A. nilotica showed significant activity against P. acnes with diameter of 8 mm, 6 mm and 4 mm inhibition zone respectively. The extracts of R. officinalis, A. nilotica and A. indica also exhibited moderate antioxidant activity with IC₅₀ value of 109.3, 136.9 and 108 μg/ml, respectively. The outcome of the study suggested that R. officinalis, M. chamomilla and A. nilotica plant extracts could be possible to use as the natural anti-acne formulations.

In a comparative study between the effectiveness of the antibiotics and medicinal plants to influence the bacteria Propionibacterium acne, Abdulhussein HH, et al. (2019) [49] showed the effect of aquatic extracts of leaves of Ocimum basilicum oil Lavandula, Azadirachata indica starting from the lowest user concentration of 100 mg/ml down to the largest inhibiting zone with a concentration of 500 mg/ml. They believe that the differential effect on pathogenic bacteria is caused by both types of use due to the characteristic chemical composition of the plants under study and the emergence of antibiotic resistance in bacteria as a result of excessive use of antibiotics or the abandonment of treatment.

Similarly, Ali MJ, et al. (2019) [50] investigated antibacterial activity for acne treatment through medicinal plants extracts including Camellia sinensis, Azadirachta indica, and Cassia acutifolia. Their results revealed that different plant extracts showed noticeable activity against different test organisms. The acetone extracts of Camellia sinensis, Azadirachta indica and Cassia acutifolia, showed higher antibacterial susceptibility of the mean of inhibition zone against bacterial isolates, reaching to 34.67, 18.76, and 12.76mm, respectively. By comparison, the antimicrobial susceptibility was exhibited by the 95% ethanolic and the aqueous extracts of medicinal plants did not exhibit an inhibitory effect against the tested microorganisms. Also, the acetonic extracts of Camellia sinensis, Azadirachta indica exhibited effective antibacterial preparation against bacterial isolates.

Mohammed RK, et al. (2020) [51] analyzed effectiveness of Thymus vulgaris alcoholic extract on Staphylococcus aureus (causative marketers of acne). In their study, special concentrations of alcoholic extract (5, 10, 15mg/ml) prompted accelerated diameters of bacterial boom inhibition zones (20, 40, 27.7, and 30mm respectively) as compared to the control (20mm). Increased diameters of inhibition zones (20.6, 32.33, 22mm) have been additionally determined in response to remedy with extraordinary concentrations of plants crucial oil (0.5, 1.5, and 2 p.c respectively) in evaluation to the manage (0.0%).

Lall N, et al. (2019) [52] examine the antityrosinase, anti-acne, antioxidant and cytotoxic potential of 25 ethanolic extracts from 16 different plant families which were collected in the Jongilanga community in the Mpumalanga province. The highest anti-acne activity was noted for Harpagophytum procumbens (Burch.) with a minimum inhibitory concentration (MIC) of 31.25?μg/mL, followed by S. brachypetala (125?μg/mL) and C. collinum, Ozoroa sphaerocarpa R. Fern and A. Fern and Pterocarpus rotundifolius DC which all showed MIC values of 250?μg/mL.

Furthermore, Esmael A, et al. (2020) [53] investigated the antibacterial activity of some plant oils against acne-inducing bacteria. In vitro investigations of eleven Egyptian plant oils, identified tea tree and rosemary oils to exhibit antibacterial activity against the antibiotic-resistant acne isolates. Tea tree and rosemary oils exhibited bacteriostatic and bactericidal activity against all the strains with MICs/MBCs ranging between 39-78 mg/L for tea tree oil and 39-156 mg/L for rosemary oil. All the isolates were killed after 4 and 6 h upon growing with 200 mg/L of tea tree and rosemary oils, respectively.

De Canha MN, et al. (2020) [54] investigated the methanolic extract of Helichrysum odoratissimum (L.) Sweet (HO-MeOH) for its ability to target bacterial growth and pathogenic virulence factors associated with acne progression. The extract showed high specificity against C. acnes cell aggregation at sub-inhibitory concentrations, preventing biofilm formation. Mature C. acnes biofilms were disrupted at a sub-inhibitory concentration of 3.91 µg/ml. At 100 µg/ml, HO-MeOH reduced interleukin-1α (IL-1α) cytokine levels in C. acnes-induced human keratinocytes (HaCaT) by 11.08%, highlighting its potential as a comedolytic agent for the treatment of comedonal acne. The extract exhibited a 50% inhibitory concentration (IC50) of 157.50 µg/ml against lipase enzyme activity, an enzyme responsible for sebum degradation, ultimately causing inflammation. The extract also inhibited pro-inflammatory cytokine levels of IL-8 by 48.31% when compared to C. acnes-induced HaCaT cells at 7.81 µg/ml. It exhibited cyclooxygenase-II (COX-II) enzyme inhibition with an IC50 of 22.87 µg/ml. Intracellular nitric oxide (NO) was inhibited by 40.39% at 7.81 µg/ml when compared with NO production in lipopolysaccharide (LPS)-induced RAW264.7 cells. The intracellular NO inhibition was potentially due to the 2.14 fold reduction of inducible nitric oxide synthase (iNOS) gene expression. The HO-MeOH extract exhibited an IC50 of 145.45 µg/ml against virulent hyaluronidase enzyme activity, which is responsible for hyaluronan degradation and scar formation.

In a randomized clinical study, Shakiba R, et al. (2019) [55] examined effectiveness of Cedar (Ziziphus spina-christi) topical solution in mild to moderate acne vulgaris in terms of acne severity index (ASI) and total acne lesions counting (TLC). In their study, the topical cedar solution plus clindamycin 1% was more effective and safe than placebo plus 1% clindamycin for the treatment of acne vulgaris.

Addiionally, Singgih M, et al. (2019) [56] investigated the antibacterial activity of water spinach (Ipomoea aquatic Forsk.) herbs extract against bacteria Propionibacterium acnes. All three extracts of water spinach herbs had better antibacterial activity against Gram-positive bacteria than Gram-negative bacteria. The ethanol-water spinach herbs extract had the best antibacterial activity against P. acnes. The minimum inhibitory concentration (MIC) value of ethanol-water spinach herbs extract on P. acnes was 1280 µg/ml while the minimum bactericidal concentration (MBC) value was >5120 µg/ml. The equivalency of ethanol-water spinach herbs extract to tetracycline hydrochloride presented 1163.87 µg ethanol extract (with density 1% extract: 0.780) equal to 1 µg tetracycline hydrochloride. All three extracts of water spinach herbs had antibacterial activity against P. acnes. They finally concluded that the ethanol extract had the best antibacterial activity against P. acnes among all three extracts.

Satpute K, et al. (2019) [57] examined effectiveness of herbal cream for treatment of acne. Their findings suggest that boswellia oil herbal formulations would inhibit the growth of P. acnes, S. epidermidis and creams showed significance antimicrobial activity against these bacteria as compared to standard.

Nelson K, et al. (2016) [58] investigated anti-acne activity of Italian medicinal plants used for skin infection. Following evaluation of 157 extracts from 10 fungi and 58 plants, they identified crude extracts from seven species exhibiting growth inhibitory activity (MICs 64-256 μg mL⁻¹). All active extracts were examined for cytotoxicity against HaCaTs; extracts from one fungal and one plant species were toxic (IC50 256 μg mL⁻¹). HPLC analysis with chemical standards revealed many of these extracts contained chlorogenic acid, p-coumaric acid, ellagic acid, gallic acid, and tannic acid. They concluded that species used in traditional medicine for the skin exhibited significantly greater (p < 0.05) growth inhibitory and biofilm eradication activity than random species, supporting the validity of an ethnobotanical approach to identifying new therapeutics. The anti-acne activity of three extracts was reported for the first time: Vitis vinifera leaves, Asphodelus microcarpus leaves, and Vicia sativa aerial parts.

Smida I, et al. (2018) [59] examined anti-acne, antioxidant and cytotoxic properties of ludwigia peploides leaf extract. In their study, a strong inhibitory activity against Propionibacterium acnes (MIC = 1.9 µg mL^-1) was registered for the extract, which had a bactericidal effect against Staphylococcus aureus, Staphylococcus epidermidis, and Salmonella enterica.

Acne vulgaris is one of the common skin problems affecting many people’s lives. In consideration of several key aspects for the therapy of acne, an integrated therapeutic approach is required to achieve the preferred reports. Many clinical researches have proven that the traditional herbs have shown very promising effects in treating the acne. The use of medicinal plants that are used by local communities, traditional healing practitioners, as well as those known to contain medicinally beneficial compounds, plays a vital role in the search for new and more effective treatments for acne.

In a nutshell, the most conventional medicinal plants used for treatment of acne are mentioned as follows: 1) Aloe ferox Mill which is from the family Xanthorrhoeaceae and its leaves and roots are topically or orally used to treat eczema, dermatitis, and acne; 2) Aloe vera (L.) Burm.f. which is from the family Xanthorrhoeaceae and its leaf gel is topically used to treat skin ailments and acne vulgaris; 3) Aspalathus linearis (Burm.f.) R. Dahlgren which is from the family Fabaceae and its leaf extract is topically used to alleviate dermatological problems associated with eczema, acne and nappy rash; 4) Bulbine frutescens Willd which is from the family Asphodelaceae and its leaf juice is taken to treat acne wounds, burns, rashes, and itches; 5) Centella asiatica (L.) Urb. which is from the family Apiaceae and its leaves and roots are topically used to prevent scar tissue and acne; 6) Glycyrrhiza glabra L. which is from the family Fabaceae and its roots are topically used to treat cysts, dermatitis, eczema, and pruritus; and, 7) Harpephyllum caffrum Bernh which is from the Anacardiaceae and its bark is topically used to treat eczema and acne. Besides, many other plants seem to have inhibitory effects on the growth of bacteria, fungi and viruses in vitro. Also, some plants have been shown to have anti-inflammatory and anti-fat properties. However, there are a few clinical evidences about the effectiveness and safety of these plants in the treatment of acne and other skin infections. For this reason, chemical drugs seem to still be the first choice in the treatment of acne and skin infections. However, the efficacy and safety of synthetic drugs are under question in the treatment of acne and other skin infections. Some plants reviewed in this paper have shown promising results. Hence, they might possibly be used alone or as adjuvant with other therapeutic measures or in mild to moderate situations. Possible contact sensitization especially in topical or oral use should be considered. Some plants, especially the roots of mountain grapes, tea tree oil, Saccharomyces, and perhaps Ocimum basilicum due to their effectiveness and safety can be compared to alternative treatments with synthetic drugs for mild to moderate acne. Further clinical studies validated with controls are required to use plants particularly the three species of eucalyptus (E. globulus, E. maculata, E. viminalis), G. glabra, U. barbata, L. minor, green tea, mountain grape root (M. aquifolium) and gluconolactone of S. bulderi, and gugulipid to treat acne. Efficacy and clinical safety trials of H. perforatum, C. sativum, B. serrata, U. barbata, R. officinalis and green tea are also essential in bacterial skin infections.

There is currently a strong focus on medicinal plants at a research level and therefore strong motivation exists for the use of these ingredients in cosmetic care products that need to be proven safe and effective with the aid of clinical research. Furthermore, mechanism of action of these plants is another important subject, which should be addressed. Phenolic compounds derived from plants have been shown to possess antibacterial activity. Most of the presented plants in this review possess these compounds. Nevertheless, in most cases it is not known how much these compounds are responsible for their anti-acne activity. It should be noted that a lot of other plants have phenolic compounds. Hence, if these compounds are solely responsible for the observed anti-acne activities, all plants with phenolic compounds should have anti-acne properties, which worth examining.

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