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Abstract

IntroductionSkin hyperpigmentation is caused by several factors (i.e., UV radiation, radicals, inflammatory mediators, and hormones) as depicted in ▶ Fig. 1. Briefly, UV radiation causes skin hyperpigmentation by stimulating keratinocytes to secrete α-MSH, a small peptide hormone derived from proopiomelanocortin. Consequently, α-MSH binds to MC1R expressed on melanocyte surfaces and thereafter induces melanogenesis via multiple signaling pathways resulting from cAMP, PKA, CREB, and MITF activity. MITF is a key transcription factor regulating the transcription of melanogenic enzymes (i.e., TYR, TRP-1, and TRP-2). In addition, UV radiation modulates Nrf2 and further activates MAPKs. MAPKs consist of three subtypes: stress-activated protein kinases/JNK, p38, and ERKs. JNK and p38 kinases are stimulated by pro-inflammatory cytokines and environmentally induced stresses such as exposure to UV irradiation, heat, and hydrogen peroxide, resulting in DNA damage. Melanogenesis is controlled by MAPKs, with MITF being activated by p38 phosphorylation. By contrast, ERK activation inhibits melanin synthesis by downregulating MITF expression [1].Preliminary evaluation of skin-whitening agents is best achieved through in vitro assays including cell culture assessments. In this context, plant-based and naturally derived skinwhitening agents have been examined for their biological activities and safety. Scientific literature provided by the American Chemical Society, J-STAGE, Karger, ScienceDirect, Taylor and Francis, Thieme Medical, and Wiley-Blackwell publishers included those that are searchable using Google Scholar published from 1997 to 2017 and cosmetic suppliersʼ databases. The literatures were searched on active, activity, bio-based, cosmeceuticals, hyperpigmentation, herb, melanin, melanogenesis, melanoma, plant, natural product, skin-lightening, and skin-whitening. Only articles in the English language have been selected. Unclear botanical identification, inadequate or insufficient data in terms of ABSTR AC T Skin hyperpigmentation is caused by several factors that upregulate melanogenesis. Plants and natural products with skin-whitening effects are gaining interest among consumers and researchers because they are perceived to be milder, safer, and healthier than synthetic alternatives. This review extensively summarizes the status of plants and natural products currently used in skin-whitening cosmetics as well as potential candidates for future use, because the scope of natural choices for efficient treatment of skin hyperpigmentation is rapidly widening. Biological activities of plants and natural extracts are therefore available for cosmetic formulators and dermatologists interested in naturally derived ingredients for skin hyperpigmentation treatment and in accordance with the consumersʼ preferences and expectations upon natural cosmetic products.