마우스 세포에서 6,7-Dihydroxy-4-methylcoumarin 화합물의 항염증 및 멜라닌 생성 효과 규명

Abstract

Coumarin derivatives such as umbelliferone, esculetin, herniarin, psoralen, and imperatorin have various physiological functions such as anti-oxidant, anti-inflammatory, anti-bacterial, anti-viral, and anti-cancer. In this study, we investigated the effect of 4-methylcoumarin related compounds on anti-inflammation and melanin in RAW 264.7 and B16F10 melanoma cells. The results showed that the dihydroxy group had antioxidant and anti-inflammatory effects, and the ortho dihydroxy group had anti-melanogenic effect, while the meta dihydroxy group had melanogenic effect. Also, the methoxy group had a melanogenic effect, and the 6-methoxy group showed the anti-inflammatory effect. Among 4-methylcoumarin related compounds, 6,7-Dihydroxy-4-methylcoumarin (6,7-DH-4-MC) showed remarkable anti-inflammatory effect, so we conducted the mechanistic study. The results showed that 6,7-DH-4-MC significantly reduced NO levels and PGE2 expression via iNOS and COX-2 down-regulation at non-cytotoxic concentrations. Moreover, 6,7-DH-4-MC dose-dependently decreased the levels of pro-inflammatory cytokines such as IL-1β and IL-6. A mechanistic studies showed that 6,7-DH-4-MC treatment reduced phosphorylation of ERK and p38-MAPK. Furthermore, the degradation of IκB-α and phosphorylation of NF-κB in LPS-treated cells were inhibited by treatment with 6,7-DH- 4-MC. In α-MSH-stimulated B16F10 melanoma cells, 6,7-DH-4-MC reduced melanin contents and tyrosinase activity without any cytotoxicity. These results suggest that 6,7-DH-4-MC is a potential therapeutic agent for inflammatory diseases and hyperpigmentation.