7, 8-dimethoxycoumarin의 피부 염증과 멜라닌 생성에 미치는 영향

Abstract

7, 8-dimethoxycoumarin (DMC, C11H10O4), a natural coumarin compound, is present in Citrus plants including Citrus decumana and grapefruit. According to previous studies have shown a protective effect against Cisplatin (CP) and ischemia-reperfusion (I/R) damage in rat kidneys. However, the mechanism of its inhibitory effects on skin inflammation in the human keratinocyte HaCaT cell and also underlying mechanisms of melanin production in B16F10 melanoma cells have not yet been investigated. In this study, the HaCaT and B16F10 cells were treated with various concentrations of DMC respectively to observe its effects. We investigated the inhibitory effects of DMC on the expression of pro-inflammatory cytokines and chemokines in TNF-α treated HaCaT cells. We found that pretreatment with DMC inhibited TNF-α-induced cytokines (Interleukin 6; IL-6) and chemokines (Interleukin 8; IL-8 and monocyte chemoattractant protein-1; MCP-1). In addition, DMC significantly inhibited TNF-α-induced NF-κB activation and phosphorylation of MAPKs, such as c-Jun N-terminal kinases (JNK) and extracellular-signal-regulated kinase (ERK). We also found that the results showed that DMC significantly increased melanin contents and tyrosinase activity without being cytotoxic in B16F10 cells. In addition, DMC stimulated the expressions of tyrosinase, tyrosinase-related protein-1 (TRP-1), tyrosinase-related protein-2 (TRP-2), and microphthalmia-associated transcription factor (MITF) thereby activating melanin production. Furthermore, to test the potential application for DMC as a cosmetic material, we also performed a primary skin irritation test on human skin. In this assay, DMC did not induce any adverse reactions at the treatment dose. Based on these results, we suggest that DMC may be considered a potential candidate for a therapeutic drug for the treatment of skin inflammatory diseases and anti-gray hair applications.