마우스 세포주에서 7-Hydroxy-4-Methlycoumarin의 항염증과 멜라닌생성 증진 효과

Abstract

7-Hydroxy-4-methylcoumarin (7H-4MC) inhibits hyaluronic acid production in multiple cell lines and tissue types both in vitro and in vivo. However, the pharmacological efficacy of 7H-4MC has not yet been reported in anti-inflammation and melanogenesis. In this study, we investigated mechanism of its anti-inflammatory effects in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages and mechanisms of melanin production in B16F10 murine melanoma cells. We investigated the inhibitory effects of 7H-4MC on the production of nitric oxide (NO) and pro-inflammatory cytokines in LPS-induced RAW264.7 cells. We found that 7H-4MC inhibited NO and pro-inflammatory cytokines production such as prostaglandin E2 (PGE2), interleukin-6 (IL-6), interleukin (IL-1β) and tumor necrosis factor-α (TNF-α). In addition 7H-4MC significantly inhibited experssion of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). 7H-4MC suppressed phosphorylation of c-Jun N-terminal kinases (JNK). 7H-4MC prevented nuclear factor-kappa B (NF-κB) activation by reducing the phosphorylation and degradation of the inhibitor κB-α (IκB-α). In addition, 7H-4MC concentration-dependently increase melanin content and tyrosinase activity without being cytotoxic in B16F10 cells. Furthermore, 7H-4MC increased the expression of proteins associated with regulating melanin synthesis such as tyrosinase-related protein-1 (TRP-1), 2 (TRP-2), tyrosinase and microphthalmia-associated transcription factor (MITF). These results suggest that possibility of 7H-4MC may be an anti-inflammatory and hypopigmentation drug.