1. INTRODUCTION:

The largest organ of the human body is skin. The skin protects us from the external environment and helps us to regulate the body temperature. It allows the sensation of touch, warmth, and cool. Most of the skin diseases arise from the layers of the skin. Skin contains number of cells and tissues and it is divided into three main layers such as epidermis, dermis, and hypodermis. The epidermis is the outer most layer of the skin and it provides a water proof barrier and makes our skin tone. The dermis is underneath the epidermis, and it contains connective tissues, hair follicles, and sweat glands. And the hypodermis is made up of connective tissue and fat. The size and colour of the skin differs from individual to individual. The skin plays an important role in overall function of the body ¹. Figure 1 represented the normally occurring skin diseases.

Numbers of infectious agents are responsible for skin diseases². Acne is the most common chronic inflammatory skin diseases of the pilosebaceous units ³. It is believed that it is the most common diseases of the skin ⁴. Approximately 95% people in the world suffer from acne vulgaris in their lifetime ⁵. Papules, pustules, opened and closed comedones, cysts, scarring may be seen. Acne can give rise to the feelings of humiliation, loss of confidence, and depression and other physical indications such as soreness and pain related with individual abrasions ^6-7.

Figure 2 exhibits the difference between a healthy hair follicle and skin with acne. In the skin with acne due to the over production of male hormone androgen and oil producing organs occurs in the face comedones. The closed comedones (whitehead) and opened comedone (blackhead) are the essential two non-inflammatory injuries in acne. When the contents are rupture, these lesions may proceed to the development of inflammatory papules and pustules. Larger size papules are more painful for example cysts and nodules may also develop ⁹. The skin portion which is rich in sebum concentration may proceed to the growth of microorganism Propionibacterium acne. In addition with Staphylococcus epidermidis and Pitryosporum ovale are present in acne lesions. Mainly P. acnes lead to the development of inflammatory lesions and severe acne. The underlying causes for acne vulgaris are different and the pathogenesis can be similar ¹⁰. Number of remedies has been used to treat acne from long period. Mostly were taken from plants and is proved to be useful. The cosmetics available in the market are unable to take for everyone thus an effort has been made to study their anti-acne activities. The product may be cost effective. This review summarized researches on various medicinal plants for its efficacy against in clinical symptoms of acne.^{11, 12}.

2. TYPES AND STAGES OF ACNE:

Acne vulgaris was classified into four categories. Category 1 contains comedones, occasional papules, category 2 comprises of papules, comedones, and few pustules, category 3 contains predominant pustules, nodules, abscesses while category 4 comprises of cysts, abscesses and widespread scarring ¹³. The severity of acne is classified into mild, moderate, and severe based on the number and type of acne lesions. There are also inflammatory and non-inflammatory types of acne. Non-inflammatory acne is a milder type in which the most people would refer to as pimples and blackheads instead of acne. Stages of acne are depicted in figure 3. Acne develops over a longer period of time and stays longer as compared to the normal pimples. In some cases it leaves small red marks or scars behind. Normal pimples usually form quickly and then leave again later. The investigations included 45 male individuals with acne vulgaris, age range between 18-30 (mean ± SD; 21.82 ± 3.77) years. Individuals were divided into three groups as indicated by the severity of acne. A mild group included 15 individuals, a moderate acne group of 15 individuals and severe acne group of 15 individuals. The severity of acne was scored according to the following rule:

Mild acne:

Individuals with mild acne have comedones (blackheads or whiteheads). The blackheads are dark in colour because this type of acne is open and the skin colour melanin responds with oxygen in the air. It has no connection with dirt. Whiteheads are closed and have a white or yellowish head. If someone has few pimples or little ones, then it is considered as mild acne. The number of papules is less than 10 and the number of pustules is less than 20.

Moderate acne:

Individuals with moderate acme have markedly more pimples. Inflamed pimples are called papules and pustules. The number of papules ranges from 10 to 30 and the number of pustules ranges from 20 to 40.

Severe acne:

Individuals with severe type of acnes have considerable number of papules and pustules and also nosodes on their skin. These nodules are often reddish and painful and the acne may consider to scarring. The number of papules is more than 30 and the number of pustules is more than 40 ^{9, 14}.

3. PATHOGENESIS OF ACNE:

Acne acts on the pilosebaceous units of the skin which presents with a variety of lesions at different inflammatory stages, including acne scars and hyperpigmentation. Acne lesions are most commonly affected on the face, chest, upper back or upper arms which shown a high density of sebaceous glands ¹⁶. The four main pathological factors required in the development of acne are the increased sebum production, irregular follicular desquamation, Propionibacterium acne proliferation and inflammation of area. These factors are outlined in figure 4.

3.1. Excess Sebum Production

The androgen hormone particularly testosterone stimulate increased production of sebum. Increased sebum production specifically correlates with the severity and occurrence of acne lesions. It is an important factor when dealing with patients suffering from acne vulgaris that ought to be taken into consideration ^{6, 17}.

3.2. Epidermal Hyper-Proliferation and Formation of Comedones

The keratinocytes in normal follicles are generally diffuse to the lumen as single cells which are then excreted. Hyperproliferation of the keratinocytes occurs in individual with acne and they are not distributed. It gathers the abnormal desquamated corneocytes in the sebaceous follicle along with different lipids and monofilaments. This phenomenon brings about the comedogenesis ¹⁸. When comedones are widened into the skin surface is called blackheads (open comedones). They seem blackish on the skin and are filled with sebum and desquamated keratinocytes. When comedones have no open pores and are appeared as white bump underneath the skin surface are termed as whiteheads (closed comedones). If the accumulation of sebum continues, the closed comedone will proceed to expand and may rupture into the encompassing tissue ¹⁹.

3.3. Propionibacterium acnes Infiltration

The microflora present in a sebaceous follicle is comparatively similar to that found in comedones. This includes three groups of microorganisms for example (1) coagulase-negative staphylococci (Staphylococcus epidermidis), (2) anaerobic diphtheroids (Propionibacterium acne and Propionibacterium granulosum) and (3) lipophilic yeasts (Pitryosporum species). Propionibacterium acne and Staphylococcus epidermidis differ in their ability to induce local skin irritation and to generate pro-inflammatory mediators. It was determined that S. epidermidis is unable to respond to the pathogenesis of inflammatory acne vulgaris skin lesions as the antibody response to S. epidermidis and it was harmless as compared to the antibodies produced by P. acnes. As S. epidermidis is an aerobe organism and their development site is superficial, it is incapable of residing in the anaerobe condition of the infra-infundibulum where the inflammatory process occurs ^{20, 21}.

3.4. Inflammation Process

The inflammatory process begins when P.acnes are identified by the immune system. P. acnes have an exceedingly inflammatory effect which may trigger the release of chemostatic factors for example, lymphocytes, neutrophils and macrophages. These components may cause follicular damage, rupture, and leakage of bacteria, fatty acids and lipids into the surrounding dermis. This procedure will give rise to inflammatory lesions (pustules, nodules, cysts, and papules). Inflammatory lesions are filled with pus and are larger than non-inflammatory lesions. Moreover, it was discovered that neutrophils generate reactive oxygen species (ROS) which partially contributes to acne inflammation by damaging the follicular epithelium. This leads to the expulsion of the follicular substance into the dermis which thus causes different inflammatory processes ^{22, 23}.

4. HERBAL TREATMENT:

Herbal medicines are increasing advanced popularity because of their points of interest, for example, better patient tolerance, long history of utilization, few side effects and being generally less expensive. Moreover, they have given great confirmation to the treatment of a wide variety of difficult to cure diseases. These plants are utilized alone or in combination with synthetic drugs to treat diseases. More essentially, other than consumption as preventive or treatment cure, they might be taken with synthetic drugs to lessen their side effects. With no exception, plant drugs are used generally, followed by different strategies or alone to treat acne vulgaris. Numerous medicinal plants with antiinflammation and antibacterial activities utilized as a part of various routes in the treatment of acne and other infective diseases ²⁶.

Berberry:

Berberis aristata, otherwise called as Indian berberry or tree turmeric, is a shrub belongs to the family Berberidaceae ²⁷. The main bioactive constituent of Berberry is the alkaloid berberine. Berberine exhibits anti-inflammatory, antibacterial, and androgen-inhibiting properties. Preliminary investigations demonstrate that it can inhibit the skin cell processes that form comedones in acne. Prasad and Kaur 2017 examined that in vitro antiacne activity of ethanolic extract of stem of Berberis aristata. Current research work is based on the effect of herbal approach to deal with acne. Acne is common disease of the skin and is usually treatable. In vitro antimicrobial screening using erythromycin as a positive control clearly showed the ethanolic extract of B. aristata is used antimicrobial against the test microorganisms ²⁸.

Basil leaves:

Ocimum sanctum (Tulsi) is an aromatic shrub in the basil family Lamiaceae. Additionally it is also known as “Queen of Herbs”. This plant exists in two varieties, i.e., Black which is also known as Krishna Tulsi, other is green known as Rama Tulsi. Therapeutically it is used in anticancer, anti-oxidant, anti-diabetic, radiations, infertility and for many other major and minor ailments. Being adaptogenic, Tulsi is used to enhance wellbeing. Extract of Tulsi utilized as a part of ayurvedic treatments for common cold, heart diseases, and stomach disorders, poisoning cases, convulsions, epilepsy, malaria, fever, bronchitis and certain inflammatory problems. Therefore, extract of Tulsi is also known as “Extract of Life” and considered to give lifespan ³⁰. Viyoch et al 2006 proposed that specific types of basil might be effective as acne treatments. He demonstrated that both sweet and holy basil oils (Ocimum basilicum and sanctum) are active against gram positive P. acnes. Holy basil extracts from leaves and oil from the seeds have anti-inflammatory properties. Minimum inhibitory concentration (MIC) values of the basil oils were determined using an agar dilution assay ³¹.

Burdock:

Arctium lappa commonly called as greater burdock. It belongs to the sunflower family ³³. Burdock is used as an alternative and cleansing herb with antimicrobial and anti-inflammatory properties that may be helpful for acne ³⁴. Miraj and Keivani 2016 determined the adequacy of homeopathic medicine Lappa in treatment of acne vulgaris. Lappa has demonstrated positive outcomes in the treatment of acne especially of inflammatory type. Besides controlled, randomized investigations with larger sample size are also desirable ³⁵, ³⁶.

Green Tea:

Green tea is procured from Camellia sinensis leaves ³⁸. Green tea is a rich source of antioxidants called as catechins. Its antioxidant activity might have the ability to encounter the oxidative activities of free radicals that is involved in the process of acne development and progression. Green tea might have the capacity to treat acne by means of numerous mechanisms ³⁹. Forest and Rafikhah 2014 stated that green tea is an ancient beverage and a popular herbal medicine. Recently, it has been utilized effectively as a topical preparation for acne patients. The objective of the present investigation was to check the viability of green tea extract in a group of patients with mild-to-moderate acne vulgaris. In this double-blind, placebo-controlled, randomized clinical trial, 34 volunteers with mild-to moderate acne vulgaris were randomly categorized in two, age and sex-matched groups, receiving either three capsules containing 500 mg aqueous extract of green tea in each (cases, n = 18), or placebo (controls, n = 16) three times daily for 30 consecutive days ⁴⁰.

Tea Tree Oil:

Tea tree oil is an essential oil that is obtained by steam distillation of the leaves of Melaleuca alternifolia (family-Myrtaceae) ⁴². The extraction of leaves of tea tree oil showed the antibacterial activity against harmful organism without affecting normal, healthy skin microbes. This includes inhibiting growth of the gram positive bacteria associated with acne Propionibacterium acnes. In laboratory experiments it is shown to kill Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) and effectively hinders simplex virus. Tea tree oil constituents also have antiinflammatory properties. Clinical investigations also showed the activity of tea tree oil against acne ⁴³. Enshaieh et al 2007 determined the ability of tea tree oil to treat mild to moderate acne vulgaris. This was randomized double-blind clinical trial performed in 60 volunteers with mild to moderate acne vulgaris. They were randomly partitioned into two groups and were treated with tea tree oil gel (n=30) or placebo (n=30). They were followed every 15 days for a period of 45 days. Response to treatment was assessed by the total acne lesions counting (TLC) and acne severity index (ASI). The data was analyzed statistically using t-test and by SPSS program ⁴⁴.

Turmeric:

Turmeric is a rhizomatous herbaceous perennial plant (Curcuma longa) of the ginger family, Zingiberaceae ⁴⁶. The naturally active component of turmeric is curcumin. Research has been demonstrated that curcumin has potent antioxidant, wound-healing, and anti-inflammatory properties which may proved to be therapeutic activity against acne ³⁶. Shah and Srivastava 2015 discussed the preliminary screenings for the antioxidant and in-vitro antiacne activities for the preparation of antiacne herbal gels. Antiacne activity was done by Paper disc diffusion method ⁴⁷.

Neem:

Neem (Azadirachta indica), a member of the Meliaceae family. Azadirachta indica contains several constituents including nimbin, nimbidin, nimbolide, and limonoids and some other types of constituents play an important part in diseases management through adjustment of different genetic pathways and other activities ⁴⁹. Shashikumar et al 2012 expressed to evaluate the safety and efficacy of Neem caplet in Acne vulgaris. This was a double blind placebo controlled clinical investigation. Fifty subjects were incorporated in the examination after satisfying all the inclusion and exclusion criteria. The criteria for assessment were reduction in comedones, inflamed papules, non inflamed papules, pustules and cysts ⁵⁰. Nand et al 2012 expressed to investigate the use of the leaves and bark of Azadirachta indica in the treatment of acne. The phytochemical screening of the extracts of leaves and bark of Azadirachta indica demonstrated that the presence of alkaloids, flavonoids, saponins, terpenes, and tannins. Gas chromatography-mass spectrometry (GC/MS) analysis of the test extracts indicated the presence of many phytoconstituents namely stigmasterol, nimbiol, sugiol, 4-cymene, α-terpinene terpinen-4-ol, and vitamin E. The test extracts were assessed against acne causing bacteria, namely Staphylococcus aureus, Staphylococcus epidermidis, and Propionibacterium acnes, for their in vitro antimicrobial activity, using agar disc diffusion method ⁵¹. Yamini and Onesimus 2013 expressed that the development and evaluation of the herbal antiacne gel containing hydroalcoholic extract of Neem leaves. The plants have good antimicrobial, anti-oxidant and anti-inflammatory activity ^{52, 53}.

Aloe Vera:

The botanical source of Aloe vera is Aloe barbadensis Miller belongs to Asphodelaceae (Liliaceae) family. Aloe vera contains many potentially active constituents’ vitamins, enzymes, minerals, sugars, lignin, saponins, salicylic acids and amino acids. Aloe vera is a natural product that frequently used nowadays in field of the cosmetology. Inspite of the fact that controlled trials are expected to determine its real efficacy. It also has anti-acne effect ⁵⁵. Bhaskar et al 2009 developed a topical poly herbal gel for the treatment of mild acne vulgaris. This method is determined using a validated HPLC method. The microbial assay demonstrated that better inhibitory activity against P. acne and S. epidermidis compared to the marketed gel ⁵⁶. Azimi et al 2012 stated that screening herbs as anti-acne agents may be used as therapy for acne ⁵⁷.

Mangosteen fruit:

The purple mangosteen (Garcinia mangostana), referred to just as mangosteen ⁵⁹. Pothitirat et al 2010 expressed that ethanol extracts of mangosteen fruit rinds prepared by several extraction methods were analyzed for their contents of bioactive compounds, DPPH-scavenging activity, and anti-acne producing bacteria against P. acnes and S. epidermidis. Mangosteen fruit extract is popularly used as a food supplement due to its antioxidant activity, while the extract from the fruit rind, promoting antibacterial properties, has been prescribed for the treatment of acne vulgaris ^60, ⁶¹.

Pippermint:

Peppermint (Mentha piperita) is a famous herb that can be utilized as a part of oil, leaf, leaf extract, and leaf water ⁶³. Peppermint also known as Mentha balsamea Willd. Family Lamiaceae is a hybrid mint, a combination of watermint and spearmint ⁶⁴. Qidwai et al 2016 expressed that antibacterial activity of Mentha piperita against P. acnes (anaerobic bacteria) ⁶⁵.

Guava:

The common guava tree (Psidium guajava) is a medium sized tree belonging to the family Myrtaceae. Traditionally guava is utilized for the treatment of different infirmities like diarrhoea wounds, rheumatism, lung problems, ulcers etc. P. guajava L. contains various pharmacologically active ingredients such as flavonoids, guayavolic acid, guavanoic acid, etc. ⁶⁷ Pandey et al 2017 expressed that to assess the in vitro antimicrobial activities of P. guajava L. leaves against P. acnes and S. epidermidis. Extraction of essential oil was carried out using Clevenger’s Apparatus. Antibacterial activities of essential oil of leaves were investigated using broth micro dilution methods recommended by CLSI. The outcomes demonstrated that Guava leaves oils more effectively inhibit the growth of P. acnes when contrasted with S. epidermidis ⁶⁸.

Caesalpinia sappan wood:

Caesalpinia sappan is a species of flowering tree in the legume family, Fabaceae. This plant has many uses. It has antibacterial and anticoagulant properties. The heartwood additionally contains juglone, which has antimicrobial activity. Homoisoflavonoids can also be found in C. sappan ^{70, 71}. Batubara et al 2010 expressed that the most potent activity of methanolic and ethanolic extracts of Caesalpinia sappan wood for treatment of acne. These extracts indicated inhibition of P. acnes growth, lipase inhibitory activity, and antioxidant activity ^{72, 73}.

Plumbago:

Plumbago auriculata is a species of flowering plant in the family Plumbaginaceae. Plumbago auriculata is a medicinal herb plant. The name has derived from the Latin word plumbum, meaning lead, because it has some pharmaceutical effects for lead poisoning. This plant is normally utilized as the treatment of wounds, broken bones, and headache. Many secondary metabolites have been discovered and isolated from Plumbago auriculata such as plumbagin, palmitic acids ⁷⁵. Kaur and Prasad 2016 proposed that anti-acne activity was examined against two acne causing bacteria, i.e., P. acnes and S. epidermidis by the well diffusion method ^76-80. Table 1 showed that number of herbal plants is used for the treatment of acne vulgaris and also showed the number of active constituents present in it.

Table1: Plants used for treatment of Acne vulgaris

S.No.	Plant	Botanical name	Family	Main Constituents	References
1	Berberry	Berberis aristata	Berbidaceae	Berberine	27, 28
2	Basil leaves	Ocimum sanctum	Lamiaceae	Eugenol, β-elemene	30, 31
3	Burdock	Arctium lappa	Asteraceae (Compositae)	lignan (neoarctin), daucosterol, arctigenin, arctiin, mataresinol, and lappaol	34, 35, 36
4	Green tea	Camellia sinensis	Theaceae	Catechins, caffeine, theobromine, gallic acid	38, 39, 40
5	Tea tree oil	Melaleuca alternifolia	Myrtaceae	1,8-cineole, terpinen-4-ol, alpha-terpineol, and gamma-terpinen	41-44
6	Turmeric	Curcuma longa	Zingeberaceae	Curcumin, demethoxycurcumin	46, 47
7	Neem	Azadirachta indica	Meliaceae	Nimbin, nimbidin, nimbolide, and limonoids	49-53
8	Aloevera	Aloe barbadensis	Liliaceae	Vitamins, enzymes, minerals, sugars, lignin, saponins, salicylic acids and amino acids	55-57
9	Mangosteen fruit	Garcinia mangostana	Clusiaceae	Vitamins and minerals, including vitamin C, phosphorus, iron, riboflavin (B12), and niacin (B3)	59, 60
10	Peppermint	Mentha piperita	Lamiaceae	Menthol, menthone, cineole, limonene, β-pinene	63-65
11	Guava	Psidium guajava	Myrtaceae	Flavonoids, guayavolic acid, guavanoic acid, etc.	67-68
12	Caesalpinia sappan wood	Caesalpinia sappan	Fabaceae	Juglone, Homoisoflavonoids	70-73
13	Plumbago	Plumbago auriculata	Plumbaginaceae	Plumbagin, palmitic acids	75, 76

5. CONCLUSION:

Most of the people in the world believe that herbal medicine is used for the treatment of many skin related problems. Traditional herbal medicine has great potential to treat different kinds of skin disorders. Allopathic medications have serious symptoms with higher cost while herbal medicines have little side effects with low cost. Acne is most occurring skin disorders mainly found in adolescents. Approximately 95% people suffer from acne vulgaris. The treatment for acne therapy is based on four well-known pathogenic factors responsible for acne. Herbal drug which are used in various medicine requires detailed information about ethnopharmacological approach. In this present review we have investigated all views related to plants used for the treatment of acne. Moreover studies going on plant give detailed description of plant constituents present and are used in herbal medicine.

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Received on 11.06.2017 Accepted on 27.06.2017

Research J. Topical and Cosmetic Sci. 8(1): Jan.-June 2017 page 40-49

DOI: 10.5958/2321-5844.2017.00005.X