BOTANICAL STUDY OF SKIN LIGHTENING AGENTSHTML Full Text
BOTANICAL STUDY OF SKIN LIGHTENING AGENTS
Shweta Katiyar * 1, Khozema Saify 2, Sanjeev Kumar Singh 1 and Meenu Rai 3
Department of Biochemistry 1, Department of Dermatology and Venereology 2, G. R. Medical College, Gwalior - 474001, Madhya Pradesh, India.
Department of Biochemistry 3, Boston College, Gwalior - 474006, Madhya Pradesh, India.
ABSTRACT: Both physicians and dermatology patients are searching for long term skin care solutions to address problems presented by skin hyperpigmentation. Traditional depigmenting agents such as hydroquinone, corticosteroids, kojic acid, although highly effective, can raise several safety concerns (for example, ochronosis, atrophy, carcinogenesis, and other local and systemic side effects) with long term exposure. An understanding of the benefits of natural and botanical extracts provides opportunities to develop new products to address pigmentation problems. This study presents an overview of trends in the application of plant extracts for the treatments of hyperpigmentation disorders. It highlights some of the potent natural products, their specific components, mode of action and optimum doses.
Hyperpigmentation, Melasma, Depigmentation agents, Free radical scavenger, Botanical extracts
INTRODUCTION: Hyperpigmentation disorders of the skin are common and can be the source of significant psychosocial distress for patients. The most common is the melasma. Melasma is a common acquired hyperpigmentary disorder that occurs mainly in women in their 30s or older (more than 90% of cases) of all racial and ethnic groups, but about 10% of cases do occur in men 1. It particularly affects those with Fitzpatrick skin types IV-VI. Multiple etiological factors include thyroid dysfunction cosmetics, phototoxic and anti-seizure drugs, ovarian dysfunction, hepatic dysfunction, nutritional deficiency, endocrinopathies, emotional factors, anti-convulsive drugs, genetics, etc. have been implicated in melasma.
Melasma presents as brown to grey macules and patches, with serrated, irregular, and geographic borders. The pigmented patches are usually sharply demarcated and symmetrical 2. Melasma has a predilection for sun-exposed areas. The three major patterns of distribution are centrofacial (cheeks, forehead, upper lip, nose, and chin) (66% of cases), malar (cheeks and nose) (20% of cases) and mandibular (rami of the mandible) (15% of cases). Based on Wood’s examination of the skin, melasma can be classified into four major clinical types and patterns, with good correlation with histology (by the depth of melanin pigment) 3: epidermal, dermal, mixed and indeterminate.
Regardless of the various types and patterns, melasma is characterized by a slight increase in the number of melanocytes and an increase in their function. The treatment of melasma is one of the most challenging from a dermatologist. As it is a common condition, it is of broad interest for control. Hypothetically, the condition is self-limiting.
However, spontaneous resolution is time-consuming and unpredictable, and it may take months to years to resolve normal pigmentation. The major problems in treating chloasma are the prolonged time to response, the inconsistency of response to treatments, and the unpredictability regarding the result after any procedure and the substantial relapse rate when the therapy is discontinued. Treating this dyschromia is also challenging due to the feared post-inflammatory hyperpigmentation after inflammation inducing therapies.
METHODS: Melasma is commonly resistant to all treatments, and is therefore very frustrating to the patient and clinician. Topical therapy can yield some improvement but rarely does it cure this condition permanently. This study is an endeavor to pile up all the traditional trends for the treatment of melasma including remedies used, type of formulation used by vaishyas and tribal people, active components of the plants, their role in the treatment of melasma and amount to be given as therapeutic against melasma. All the plants are collected and kept in herbarium for further studies. The herbarium is authenticated from the botanist of Central Ayurvedic Research Institute, Gwalior, Madhya Pradesh.
RESULTS: The results are concluded in Table 1 as:
TABLE 1: LIST OF SOME OF THE POTENT NATURAL PRODUCTS, THEIR SPECIFIC COMPONENTS, MODE OF ACTION AND OPTIMUM DOSES
|Aloe||Aloe barbedensis||Liliaceae||Leaves||Aloesin||↓Tyrosinase competitively, ↓ DOPA polymerase||125 -500
|Banyan||Ficus benghalensis||Moraceae||Bark, fruits||Flavonols, triterpene,||Free radical scavenger||3-5 gm / kg|
|Tyrosinase inhibitor||13-25 centigrams|
|Bearberry||Arctostaphylos uva-ursi||Ericaceae||Leaf extract||Polyphenolic compounds, arbutin||↓ Tyrosinase,
↓ DHICA polymerase
|100 mg / kg|
|Bilberry||Vaccinium cyanooccus||Ericaceae||Leaf, fruits||Arbutin, anthocyanin,
↓ DHICA polymerase
|100 mg / kg|
|Blueberry||Vaccinium myrtillus||Ericaceae||Fruits||Anthocyanoside, tannins, hydroxyl benzoic acids, flavonol glycosides||Antioxidative effects||4-8 gm|
|Peel||Polymethoxy flavonoids||Antioxidant activity||1 ml|
|Seed oil, leaves||Ricinoleic acid
|Free radical scavenger||5-20 ml
|Heartwoodleaves||Phenolic compounds, flavonoids||Antioxidant activity||20-30 gm|
|Free radical scavenger||2-3 gm|
|Allantoin, poly[oxy-1-carboxy-2-(3,4-dihydroxypheny) nethylene||Free radical scavenger||Topical|
|Seed, Fruit juice||Rutin, ascorbic acid oxidase, cucurbit-aside||Free radical scavenger||3-6 gm,
|Apiaceae||Seed||The flavonoid, p-cymene cuminaldehyde.||Free radical scavenger||1-3 g powder.
|Seed Extract||Anthocyanin||Antioxidant activity||100 µg /ml|
|Onagraceae||Seed oil||γ – Linolenic acid||↓mRNA level of Tyr. Related Protein 1 & 2.||4-8 gm|
|Flame of the forest||Butea
|Fabaceae||Flower, fruits||Flavonoids, steroids||Free radical scavenger||100-400
|Geraniaceae||Leaves, oil||Geraniin, kaempferol, flavonoid||antioxidative effects, inhibitory effects on elastase and tyrosinase||15 µg/ml|
|Gooseberry||Phyllanthus emblica||Euphorbiaceae||Extract, fruit||Vitamin C, Superoxide dismutase||↓Tyrosinase, the antioxidant of collagen||10-20 gm|
|Flavonoids, Tannin||Tyrosinase inhibitor||5-10 gm|
|Greenleaf manjanita||Aractostaphylos patula||Ericaceae||Leaves||Polyphenolic compounds||Tyrosinase inhibitor,exhibit Superoxide dismutase||-|
|Horse-radish||Armoracia lapathifolia||Brassicaceae||Roots||Phenolic compounds||Free radical scavenger||3-5 gm|
|Roots||p-Coumaric acid||↓ L-Tyrosinase oxidation||200-500
|Indian Sarsaparilla||Hemidesmus indicus||Asclepiadaceae||Roots,
|Free radical scavenger||20-30 gm|
|Sopohora flavescens||Fabaceae||Fruits||Sophocarpine||↓ Tyrosinase activity||-|
|↓Tyrosinase, the antioxidant of collagen||5-10 ml./kg|
|Lodh tree||Symplocos racemosa||Symplocaceae||Bark||Alkaloids
(lot urine, loturidine,)
|Antioxidant activity, lipid peroxidation inhibition||3-5 gm/kg|
|Luteolin/luteolin-7-glucoside, flavonoids||Free radical scavenger||10-20 ml|
|Ginkgoaceae||Leaves, root bark||Flavonoid glycosides, terpenoids||Neutralize free radicals||200 mg per day
|Mangostin||Garcinia mangostana||Guttiferae||Peri carp||γ – mangostin, tanin||Free radical scavenger||10-60 grains|
|Root||Rubiadin||Free radical scavenger||200-400 mg|
|Marigold||Calundula officinalis||Asteraceae||Flower||Coumarins, flavonoids||Free radical scavenger||0.20 µg/ml|
|Achillea millefollum||Asteraceae||Extract, oil||Eucalyptol, camphor,
|Free radical scavenger, effects on lipid peroxidation||0.25-7.5
|Leaves||Flavonoids, mulberroside F||Tyrosinase inhibitor, a Superoxide scavenger||5-10 gm|
|Mulethi/ Licorice||Glycyrrhiza glabra||Fabaceae||Roots||Glabridin, glycyrrhizin||Free radical scavenger||2-4 gm/kg|
|Bulbs||Quercetin||Antioxidant activity||10-20 ml|
|Papaya||Carica papaya||Caricaceae||Latex||Papain, chymopapain, carpaine, pseudocarpaine||Free radical scavenger||40-50 ml|
p-coumaric acid, flavonoids
|100 mg per kg|
|Stigma||Carotenoids, Crocetin||Free radical scavenger||50-100 mg|
|Alpha-and beta-santalol.||↓ DNA damage,
|Siris , benth||Albizzia
|Bark, leaves||Flavonoids, saponins||Free radical scavenger
|Whole plant||Vitamin C, B,
soy protein, Isoflavone
|Inhibit protease-activated receptor 2 pathway||-|
luteolin-7-glucoside and asteroids
|Free radical scavenger, lipid peroxidation inhibiton||-|
|Seed oil||Vitamin E, helianol||Anti-inflammatory||30 µg/ml|
|Acoraceae||Rhizome, oil||Asarone||Antioxidant activity||400 mg/kg|
|Sweet Marjoram.||Origanum majorana||Labiatae||Oil||Hydroxyquinone, flavonoid||Superoxide anion radical scavenger||1.44 µg/ml|
|Free radical scavenger||1-3 gm|
|Watercress||Enhydra fluctuans||Compositae||Leaf||Beta carotene||Antioxidant activity||3.6-4.2 mg/100g|
In the present study, we conclude that about 49 plants of 31 genera have potential activity against melasma. The plants are listed by their botanical names, recommended doses, depigmenting mechanism, chemical constituents, and their other functions also. These plants are used in the form of therapeutics and topical, on the affected skin. The parts of the plant most used for medicinal purposes are leaves, root, stem, fruits, the complete aerial parts, the whole plant, barks (root and stem) and flowers (including the flowering heads) in decreasing order. Juice (almost mix with water and goat's or cow's milk) and paste are the main methods of preparation, either for oral or for external administration. For topical use, the most important methods used are a direct application of the paste or ointment (with oil). The Ayurvedic clinicians medicate these remedies because Ayurveda is the ancient medicinal custom of India. Ayurveda is a good supplement of regional medicinal values. Tribes are using these remedies very frequently, and 76% of patients even concern the allopathic clinicians.
DISCUSSION: In the search for novel depigmenting agents, the investigation of natural plant extracts has led to the identification of many potentially active compounds. Many plant extracts are potent inhibitors of melanin formation and not associated with cytotoxicity or mutagenicity of melanocytes 4. These plants work against melasma because they have multiple chemical components like arbutin, aloesin, flavonoids, niacinamide, vitamins, etc. which inhibit the melanin formation.
Arbutin: Arbutin, a naturally occurring β-D-glucopyranoside derivative of hydroquinone, exists in the dried leaves of certain plant species, such as bearberry. The mode of action appears to be by inhibition of melanosomal tyrosinase and DHICA (5, 6- dihydroxyindole-2-carboxylic acid) poly-merase activities at noncytotoxic concentrations rather than by suppression of the synthesis and expression of this enzyme 5, 6. Studies have shown that a-arbutin (4-hydroxyphenyl a-glucopyranoside) demonstrates an even stronger inhibitory effect on human tyrosinase activity than arbutin itself. Deoxyarbutin (dA, 4-[tetrahydrofuran-2-yl-oxy]-phenol) has also demonstrated effective inhibition of mushroom tyrosinase in-vitro 7.
Aloesin: Aloesin, a compound isolated from the aloe plant, has been proven to competitively inhibit tyrosinase from human, mushroom, and murine sources. Studies have shown that tyrosine hydroxylase and DOPA (3, 4-dihydroxy phenylalanine) oxidase activities (of tyrosinase from normal human melanocyte cell lysates) are inhibited by aloesin in a dose-dependent manner2. The topical application of aloesin on UV-irradiated (210 mJ) human volar forearm (four times a day for 15 days) showed pigmentation suppression in a dose-dependent manner 3. Aloesin, along with arbutin, was observed to synergistically inhibit melanin production by combined mechanisms of noncompetitive and competitive inhibitions of tyrosinase activity 8.
Flavonoids: Flavonoids are polyphenolic compounds that are ubiquitous and are categorized, according to chemical structure, into flavonols, flavones, flavanones, isoflavones, catechins, anthocyanidins, and chalcones. The effects of many flavonoids on the oxidation of L-DOPA have been studied. Isoflavones, including glycitein, daidzein, and genistein, showed little antityrosinase activity, but 6, 7, 4΄-trihydroxyisoflavone has been identified as a potent tyrosinase inhibitor stronger than kojic acid. Flavanones, such as hesperidin, eriodictyol, and naringenin, have a structure that is similar to that of hydroquinone 9. Dr. Buhler and Miranda reported that flavonoids might be potentially useful in the prevention of human diseases attributed to free radical damage. The observation that prenyl groups are important in conferring antioxidant activity to certain flavonoids may lead to the discovery or synthesis of novel prenylated flavonoids as preventive or therapeutic agents against human diseases associated with free radicals.
Hesperidin: Hesperidin is a bioflavonoid existing extensively in the peel and membranes of citrus fruits. Studies by Zhu and colleagues have demonstrated hesperidin’s potent ability to inhibit melanin synthesis without cytotoxicity. Also, hesperidin was found to protect against UVA-induced damage of fibroblasts and oxidative damage of collagen 10. Thus, hesperidin offers potential skin-lightening benefits, including improved overall skin tone and antiyellowing effects.
Niacinamide: Niacinamide is a biologically active form of niacin (vitamin B3) found widely in many root vegetables and yeasts, and it is also an important precursor of NADH (nicotinamide adenine dinucleotide) and NADPH (nicotinamide adenine dinucleotide phosphate). A large number of cellular enzyme reactions in which these cofactors participate may be the basis for the variety of cosmetic benefits, including barrier enhancement observed from the topical use of niacinamide 11.
Using cocultures of human melanocytes and keratinocytes, investigators have shown that niacinamide inhibits the transfer of melanosomes from melanocytes to keratinocytes. Results of clinical studies using topically applied niacinamide have demonstrated a reversible reduction in hyperpigmented lesions and increased skin lightness compared with vehicle alone after 4 weeks of use. In a separate clinical study, topical niacinamide was also shown to decrease collagen oxidation products and improve aging-induced yellowing or sallowness 12.
Glabridin: Glabridin, the main ingredient in the hydrophobic fraction of licorice extract, inhibits tyrosinase activity, without affecting DNA synthesis. Other active compounds, such as glabrene, isoliquiritigenin licuraside, isoliquiritin, and licochalcone A, isolated from licorice extracts, were also shown to inhibit tyrosinase activity 13, 14. Liquiritin does not affect tyrosinase; however, it causes depigmentation by other mechanisms, and studies demonstrate that a 20% liquiritin cream applied at 1 g /day for 4 weeks is therapeutically effective in melasma 15.
Polyphenols: Polyphenols are a class of compound that has the antioxidant capacity and are found widely within plants. The inhibition of melanogenesis has been observed with many types of polyphenol plant extracts. Proanthocyanidins or procyanidins, classified as polyphenols, exist in red wine and cranberry juice; grape seeds are another especially rich source. The antioxidative activities of proanthocyanidins were found to be much stronger than the activity of vitamin C or E in aqueous systems. Ellagic acid is another natural polyphenol that is widely found in fruits and vegetables. The extract of the rinds of pomegranate contained 90% ellagic acid and showed inhibitory activity. The mechanism of action may be inhibition of the proliferation of melanocytes and melanin synthesis by tyrosinase in melanocytes 16.
P-Coumaric Acid: P-coumaric acid, extracted from the fresh leaves of Panax ginseng, was shown to inhibit the oxidation of L-tyrosine more strongly than the inhibition of tyrosinase demonstrated by L-DOPA 17. Treatment with ginseng in the presence of various concentrations of Radix trichosanthin suppressed tyrosinase activity and melanin content but increased cell proliferation slightly in melanoma cells, raising the possibility that this combination may be effective as a skin-lightening agent 18.
CONCLUSION: Melasma poses a substantial emotional and psychosocial burden on patients. Many undergo multiple therapies, from cosmetic treatments to ineffective or even aggressive medical treatments that do not solve their problem or even make it worse. Some patients spend a fortune on treatments over the years. Others hideaway, feeling ashamed and stigmatized. Even though melasma is a benign and easily diagnosed disease, clinicians must rule out melanoma and its precursors and must be able to distinguish and diagnose skin manifestations of systemic diseases.
During the past decades, thousands of plant extracts have been screened, and hundreds of compounds were identified as potential skin-lightening ingredients. It is clear that natural sources and extracts represent a repository of ingredients that can be used in topical treatments to achieve improvement of hyperpigmentation and the overall appearance of skin. These ingredients may also provide additional potential for protective cosmeceutical use, through antioxidant efficacy and protection of macromolecules, such as collagen from UV irradiation. With natural sources offering a multitude of different extracts and isolated compounds, it is apparent that we are only beginning to realize the potential of natural extracts for skin lightening applications.
ACKNOWLEDGEMENT: I owe a great many thanks to a great many people who helped and supported me during the writing of this paper.
My deepest thanks to Dr. (Mrs.) Meenu Rai, (Professor, Jiwaji University) (Guide) for their guiding and correcting various documents of mine with attention and care. She has taken the pain to go through the project and make necessary correction as and when needed.
My deep sense of gratitude to Dr. S. K. Singh (Associate Professor, G. R. Medical College) and Dr. Khozema Saify (Assistant Professor, G. R. Medical College) for their support and guidance. Thanks and appreciation to the helpful people of G. R. Medical College, Gwalior, for their support.
CONFLICT OF INTEREST: Nil
- Grimes PE: Melasma. Etiologic and therapeutic considerations. Arch Dermatol 1995; 131: 1453-1457.
- Jones K, Hughes J, Hong M, Jia Q and Orndorff S: Modulation of melanogenesis by aloesin: a competitive inhibitor of tyrosinase. Pigment Cell Res 2002; 15: 335-40.
- Choi S, Lee SK, Kim JE, Chung MH and Park YI: Aloesin inhibits hyperpigmentation induced by UV radiation. Clin Exp Dermatol 2002; 27: 513-5.
- Zhu W and Gao J: The use of botanical extracts as topical skin lightening agents for the improvement of skin pigmenting disorders: Journal of Investigative Dermatology 2008; 13: 20-24.
- Maeda K and Fukuda M: Arbutin: mechanism of its depigmenting action in human melanocyte culture. J Pharmacol Exp Ther 1996; 276: 765-9.
- Chakraborty AK, Funasaka Y, Komoto M and Ichihashi M: Effect of arbutin on melanogenic proteins in human melanocytes. Pigment Cell Res 1998; 11: 206-12.
- Boissy RE, Visscher M and DeLong MA: DeoxyArbutin: a novel reversible tyrosinase inhibitor with effective in-vivo skin lightening potency. Exp Dermatol 2005; 14: 601-8.
- Jin YH, Lee SJ, Chung MH, Park JH, Park YI and Cho TH: Aloesin and arbutin inhibit tyrosinase activity in a synergistic manner via a different action mechanism. Arch Pharm Res 1999; 22: 232-6.
- Tiedtke J, Morel J and Marks O: Depigmentation factor. Bioflavonoids- a safe and effective skin lightener based on encapsulated citrus bioflavonoids. Cosmetochem 2004; 12-7.
- Proteggente AR, Basu-Modak S, Kuhnle G, Gordon MJ, Youdim K and Tyrrell R: Hesperetin glucuronide, a photoprotective agent arising from flavonoid metabolism in human skin fibroblasts. Photochem Photobiol 2003; 78: 256-61.
- Hakozaki T, Minwalla L, Zhuang J, Chhoa M, Matsubara A and Miyamoto K: The effect of niacinamide on reducing cutaneous pigmentation and suppression of melanosome transfer. Br J Dermatol 2002; 147: 20-31.
- Bissett DL, Miyamoto K, Sun P, Li J and Berge CA: Topical niacinamide reduces yellowing, wrinkling, red blotchiness, and hyperpigmented spots in aging facial skin. Int J Cosmet Sci 2004; 26: 231-8.
- Fu B, Li H, Wang X, Lee FS and Cui S: Isolation and identification of flavonoids in licorice and a study of their inhibitory effects on tyrosinase. J Agric Food Chem 2005; 53: 7408-14.
- Nerya O, Vaya J, Musa R, Izrael S, Ben-Arie R and Tamir S: Glabrene and isoliquiritigenin as tyrosinase inhibitors from licorice roots. J Agric Food Chem 2003; 51: 1201-7.
- Amer M: Metwalli: Topical liquiritin improves melasma. Int J Dermatol 2000; 39: 299-301.
- Yoshimura M, Watanabe Y, Kasai K, Yamakoshi J and Koga T: Inhibitory effect of an ellagic acid-rich pomegranate extract on tyrosinase activity and ultraviolet-induced pigmentation. Biosci Biotechnol Biochem 2005; 69: 2368-73.
- Lim JY, Ishiguro K and Kubo I: Tyrosinase inhibitory p-coumaric acid from ginseng leaves. Phytother Res 1999; 13: 371-5.
- Im SJ, Kim KN, Yun YG, Lee JC, Mun YJ and Kim JH: Effect of Radix dinseng and Radix trichosanthis on the melanogenesis. Biol Pharm Bull 2003; 26: 849-53.
How to cite this article:
Katiyar S, Saify K, Singh SK and Rai M: Botanical study of skin lightening agents. Int J Pharmacognosy 2014; 1(4): 243-49. doi link: http://dx.doi.org/10.13040/IJPSR.0975-8232.IJP.1(4).243-49.
This Journal licensed under a Creative Commons Attribution-Non-commercial-Share Alike 3.0 Unported License.
S. Katiyar ⃰, K. Saify , S. K. Singh and M. Rai
Department of Biochemistry, G. R. Medical College, Near Katora Taal, Gwalior, Madhya Pradesh, India.
07 January 2014
28 February 2014
31 March 2014
01 April 2014