마우스 세포에서 6-Methylcoumarin의 항염증 및 멜라닌 생성 효과 규명

Abstract

In this study, we investigated the structural differences of 6-methylcoumarin (6-MC), 7-methylcoumarin (7-MC), 4-hydroxy-6- methylcoumarin (4H-6-MC), 4-hydroxy-7-methylcoumarin (4H-7-MC) for anti-inflammatory and melanogenesis effects in RAW 264.7 cells and B16F10 melanoma cells. Because 6-MC had the best anti-inflammatory and melanogenesis effects, we conducted a mechanism study in RAW 264.7 cells and B16F10 melanoma cells. As a result, 6-MC reduced the production of inflammatory mediators, nitric oxide (NO) and prostaglandin E2 (PGE2), and significantly reduced the production of pro-inflammatory cytokines Interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α). Furthermore, western blot results showed that the expression levels of iNOS and COX-2 decreased in a concentration-dependent manner during 6-MC treatment, and the phosphorylation of mitogen-activated protein kinase (MAPKs) was also suppressed in a concentration-dependent manner. It also suppressed the phosphorylation of IκB-α and transfer of NF-κB from the cytoplasm to the nucleus. In B16F10 melanoma cells, 6-MC increased melanin content and tyrosinase activity in the absence of cytotoxicity. As a result of western blot, protein expression of tyrosinase-related protein-1 (TRP-1), TRP-2, and microphthalmia-associated transcription factor (MITF) was increased upon treatment with 6-MC. In addition, 6-MC showed inhibition of ERK phosphorylation and AKT phosphorylation. These results suggest that 6-MC is a potential treatment for anti-inflammatory and hypopigmentation.