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Pdf 991.71 K Research Journal of Pharmacognosy (RJP) 4(4), 2017: 71-85 Received: 14 Dec 2016 Accepted: 24 June 2017 Review article Plants used to treat hyperpigmentation in Iranian traditional medicine: a review S. Ghafari1, Sh. Fahimi2*, Sh. Sahranavard2 1Traditional Medicine and Materia Medica Research Center (TMRC), Shahid Beheshti University of Medical Sciences, Tehran, Iran. 2Department of Traditional Pharmacy, School of Traditional Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Abstract Skin hyperpigmentation is characterized as increased production and accumulation of melanin, which could be aesthetically unfavorable and develops serious skin diseases. There is a need to find new depigmenting agents, since many current natural and synthetic products present undesired side effects. In Iranian traditional medicine (ITM), plants have been used for the treatment of skin diseases such as hyperpigmentation. In this study, topical herbal medicines, for the treatment of hyperpigmentation were searched in ITM references, and their scientific names were identified, using different comprehensive glossaries. Thereafter, depigmenting mechanisms of these genera were reviewed in recent scientific literatures. Seventy-nine plants were made known as herbal remedies for skin hyperpigmentation. Furthermore, modern literatures have shown depigmenting effect of about 40% of these plants or their isolated compounds, with different melanogenesis inhibitory mechanisms with tyrosinase inhibition as the most revealed method. Regarding the new approach to medicinal plants in recent years, a large number of medicinal herbs that were mentioned in ITM references would be good candidates for exploring new herbal medicines for skin hyperpigmentation disorders. Keywords: herbal medicine, hyperpigmentation, Iranian traditional medicine Introduction Skin pigmentation is a broad term, usually occur widely in the human population, and are reflecting an increased and dispersion of melanin, considered to be skin disorders and cause the pigment that gives human skin, hair, and eyes psychological disturbances [4]. their color [1,2]. Epidermal and dermal Since skin hyperpigmentation is related to the hyperpigmentation can be dependent to either chemical nature of melanin, tyrosinase activity, increased numbers of melanocytes or activity of tyrosinase-related protein-1 (TRP-1) and melanogenic enzymes [3]. Hyperpigmentary tyrosinase-related protein-2 (TRP-2) in the problems such as post inflammatory, melanocytes, and the transfer of melanin in the hyperpigmentation, solar lentigo, and melasma, keratinocytes, several treatment methods such as © Available at: http://rjpharmacognosy.ir Copy right 2014 by the Iranian Society of Pharmacognosy *Corresponding author: [email protected], Tel/Fax: +98 21-88776027 Ghafari S. et al. inhibition or attenuation of tyrosinase and related as Rhazes and Avicenna were merging all melanogenic enzymes catalytic activity, existing information on medicine at that time, transcriptional regulation and post-translational and have also theorized their own examination modification of melanogenic enzymes, and wise perception [12]. interruption of melanosome transfer, acceleration In ITM references, the most used terms of epidermal turnover have been investigated denoting skin hyperpigmentation are ‘Kalaf’, [2,5]. ‘Bahaq’ and ‘Namash’ [13-16]. Review of Tyrosinase is the key enzyme of melanogenesis Iranian Traditional Medicinal books showed that and the first in the conversion of tyrosine to ‘Kalaf’ was a kind of skin darkness or brown to melanin. It is a common target for therapeutic black pigmentation that usually occurred on the agents intended to alleviate cutaneous face with clinical manifestations similar to hyperpigmentation. By using purified mushroom melasma [17,18]. ITM scholars believed that tyrosinase or cell lysates of melanoma cells ‘Bahaq’ was similar to ‘Kalaf’ except that tyrosinase inhibitory effect could be determined ‘Bahaq’ was associated with sloughing and [2]. Mushroom tyrosinase, the enzyme extracted roughness [15]. According to humoral theory in from the champignon mushroom Agaricus ITM, abnormal black bile congestion in skin bisporus, is highly homologous and layers and its increased concentration caused commercially available, thus making it well dark color spots on the face, known as “Namash” suited as a model for studies on melanogenesis, being equivalent to freckles [19]. and has been used by many studies carried out on There are many medicinal plants, which have tyrosinase inhibition [2,5]. been utilized for the treatment of Hydroquinone and its derivations, such as hyperpigmentation by Iranian physicians, which arbutin, and kojic acid are some of the common are yet to be fully verified experimentally. and effective whitening agents to treat In this study, the medicinal plants used for the hyperpigmentation disorders with mechanism of treatment of hyperpigmentation in ITM inhibition of tyrosinase [6,7]. In spite of their references via topical route of administration efficacy, the mentioned whitening agents would were reviewed. Subsequently, melanogenesis cause some adverse effects such as sensitization, inhibitory effects of these species were searched contact dermatitis and erythema and also in recent scientific literatures. cytotoxic and mutagenic effect with prolonged exposures [4,8]. Methods The long-term use of herbs, introduced in Traditional search traditional medicines, confirms their value in Three famous books including Liber continens, drug discovery [9]. Surprisingly, many crude the Canon of medicine and Makhzan-ul-adviah drug and plant extracts have been reported to were selected as the main references of ITM. inhibit the tyrosinase enzyme [4]. The “return to nature” trend of recent years had been Liber continens (al-Hawi fi al-tibb) accompanied by a thriving interest in whitening Abu Bakr Muhammad ibn Zakariya Razi agents from herbal medicine [10] with most of (Rhazes), a renowned Iranian physician, chemist the population still believing in traditionally and philosopher (865–940 A.D.) wrote the book crude drugs and medicinal plants to treat of al-Hawi fi al-Tibb. This book is the most hyperpigmentation [4]. important book of Rhazes, and was repeatedly Iranian traditional medicine (ITM), which dates printed in Europe during the 15th and 16th back to over 6000 years [11], was a combination centuries, under the title ‘Liber Continens’. It had of different medical traditions from Greece, a major influence on the development of medical Egypt, India and China. Iranian physicians such practices in Europe. Rhazes surveyed Greek and 72 RJP 4(4), 2017: 71-85 Plants for treatment of hyperpigmentation in ITM early Arabic medicine, as well as various Indian Thereafter, plants were identified by different medical knowledge. Furthermore, during his comprehensive glossaries by matching their work, he added his own considered judgment and traditional names with scientific names [23,24]. medical experience as commentary [9]. Modern search The Canon of medicine Plants with melanogenesis inhibitory effect in The Canon of medicine is the best work on modern scientific databases traditional medicine, which was compiled by Abu In order to find melanogenesis inhibitory effect Ali Al- Hussain ibn-e Abdullah- ibn-e- Sina, of the plants, a substantial search of scientific known as Avicenna, one of the most famous databases such as ‘Google Scholar’, ‘Scopus’ and Iranian physician (980-1037 A.D.). The Canon of ‘PubMed’ was carried out, using the genera in medicine was used in over half a century in combination with key terms such as European scientific centers as a medical ‘hyperpigmentation’, ‘melanogenesis’ and textbook, and was later translated into different ‘tyrosinase’. languages [20]. It consists of five books, and serves as a concise reference in traditional Results and Discussion medicine. The second book contains an estimate Based on the ITM references, about 71 traditional of 800 individual drugs, mostly of medicinal names of medicinal plants, applied to treat skin hyperpigmentation (‘Bahaq’, ‘Kalaf’and plants (and some animal and mineral substances). ‘Namash’) via topical route of administration Avicenna added his own comments, highlighting were found. The plants have been listed based on the differences between recipes from different their scientific names. Moreover, their repetition sources, and occasionally, there were some in the Canon of medicine, Liber continens and disagreement regarding them. Thus, he gave his Makhzan-ul-adviah along with the traditional opinion of the effectiveness (or ineffectiveness) names of the plants, phonetic spellings, families of some remedies [21]. and used organs have been shown (table 1). In modern literatures, all of the plants mentioned Makhzan-ul-adviah in table 1 were searched for hyperpigmentation Makhzan-ul-adviah written by Aghili Alavi inhibitory effect, and the mechanisms of Khorasani, one of the prominent Persian interference with melanin synthesis according to physicians (1772 A.D.), is a significant reference their genera. The results are as follows: about traditional medicine and medical terminology in Persian. About 1744 individual drugs of plant, mineral and animal origin used in Tyrosinase inhibition traditional medicines, have been described in Quercetin-3'-O-β-D-glucoside was isolated from Makhzan-ul-adviah. It is a collection of his Allium cepa and inhibited melanogenesis without lifetime medical notes, summarized from cytotoxicity. It
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