The role and mechanism of Asian medicinal plants in treating skin pigmentary disorders.

ETHNOPHARMACOLOGICAL RELEVANCE: Chloasma, senile plaques, vitiligo and other pigmentary disorders seriously affect patients' appearance and life quality. Medicinal plant is the product of long-term medical practice worldwide, with the advantages of outstanding curative properties and less side effects. Recently, research were made to explore the value of medicinal plants in the treatment of pigmentary disorders, and remarkable results were achieved. AIM OF THE REVIEW: This review outlines the current understanding of the role and potential mechanisms of medicinal plants (including active ingredients, extracts and prescriptions) in pigmentary disorders, especially Chinese medicinal plants, provides the preclinical evidence for the clinical benefits. This study hopes to provide comprehensive information and reliable basis for exploring new therapeutic strategies of plant drugs in the treatment of skin pigmented diseases. METHODS: The literature information was obtained from the scientific databases (up to Oct, 2017), mainly from the PubMed, Web of Science and CNKI databases, and was to identify the experimental studies on the regulating melanogenesis role of the active agents from herbal medicine and the involved mechanisms. The search keywords for such work included: "pigmentary" or "pigmentation", "melanogenesis", and "traditional Chinese medicine" or "Chinese herbal medicine", "herb", "medicinal plant". RESULTS: We summarized the function of medicinal plants involved in melanogenesis, especially Chinese medicine. It was reported that the active ingredients, extracts, or prescriptions of medicinal plants can regulate the expression of genes related to melanogenesis by affecting the signaling pathways such as MAPK and PKA, thereby regulating pigment synthesis. Some of them can promote melanogenesis (such as isoliquiritigenin, geniposide; Cornus officinalis Siebold & Zucc., Eclipta prostrata (L.) L.; the Bairesi complex prescription, etc.). While others have the opposite effect (such as biochanin A, Gomisin N; Panax ginseng C.A. Meyer, Nardostachys chinensis Bat.; Sanbaitang, etc.). CONCLUSION: Asian medicinal plants, especially their active ingredients, have multilevel effects on melanogenesis by regulating melanogenesis-related genes or signaling pathways. They are of great clinical value for the treatment of skin pigmentary disorders. However, the experimental effect, safety, and functional mechanism of the medicinal plants require further determination before studying their clinical efficacy.

Ganoderma lucidum polysaccharide reduces melanogenesis by inhibiting the paracrine effects of keratinocytes and fibroblasts via IL-6/STAT3/FGF2 pathway.

Our previous study found that Ganoderma lucidum polysaccharide (GLP), bioactive ingredients from Ganoderma lucidum, protected fibroblasts from photoaging. However, whether GLP can affect melanogenesis in melanocytes through regulating paracrine mediators that secreted by keratinocytes and fibroblasts is unclear. We aimed to investigate the efficacy and mechanisms of action of GLP in melanogenesis by regulating paracrine effects of keratinocytes and fibroblasts. The effect of GLP on cell viability affected by GLP was measured by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. After an immortal keratinocyte line (HaCaT) and primary fibroblasts (FB) were treated with GLP, the supernatants of HaCaT and FB cells were collected and cocultured with an immortalized melanocyte line (PIG1). The expression levels of melanogenesis-associated genes in PIG1 cells were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis. Furthermore, FRS-2, ERK, JNK, and p38 phosphorylation levels were measured. Then, major melanogenic paracrine mediators in HaCaT and FB cells treated with GLP were evaluated by qRT-PCR and enzyme-linked immunosorbent assay (ELISA). In addition, the expression of IL-6 and STAT3 was examined in HaCaT and FB cells. GLP was not cytotoxic to HaCaT and FB cells. The supernatants of GLP-treated HaCaT and FB cells downregulated the expression levels of MITF, TYR, TYRP1, TYRP2, RAB27A, and FSCN1 genes and inhibited the phosphorylation of FRS-2, ERK, JNK, and p38 in PIG1 cells. GLP also decreased FGF2 secretion in HaCaT and FB cells. Moreover, GLP reduced IL-6 expression and STAT3 phosphorylation in HaCaT and FB cells. GLP reduced melanogenesis in melanocytes by inhibiting the paracrine effects of keratinocytes and fibroblasts via IL-6/STAT3/FGF2 pathway.