Flavonoid 계열 화합물 Chrysoeriol과 Linarin의 멜라닌 합성 증진 규명

Abstract

Chrysoeriol (4',5,7-trihydroxy-3'-methoxyflavone) and linarin (5-Hydroxy-4'-methoxyflavone-7-O-rutinoside) are flavonoid compounds commonly found in nature. In this study, we investigated the melanogenesis and mechanism of chrysoeriol and linarin in B16F10 murine melanoma cells. The B16F10 cells were treated with various concentrations of chrysoeriol (1, 2, 4 and 8 μM) and linarin (5.25, 10.5, 21 and 42 μM) respectively to observe its effects. In the concentration range without cytotoxicity, chrysoeriol and linarin concentration-dependently increase melanin content and tyrosinase activity in B16F10 cells. To confirm the expression of melanogenic enzymes expresstion and its mechanism study, we performed western blot analysis. The results showed that chrysoeriol and linarin increased the expression of proteins associated with regulating melanin synthesis such as tyrosinase, tyrosinase-related protein-1 (TRP-1) and 2 (TRP-2). In this regard, treatment with chrysoeriol and linarin also increased the expression of microphthalmia-associated transcription factor (MITF). Chrysoeriol and linarin inhibited the degradation of MITF through inhibition of extracellular signal-regulated kinases (ERK) phosphorylation and also upregulated MITF by inhibiting phosphorylation of protein kinase B (AKT). Additionally, chrysoeriol inactivitated glycogen synthase kinase 3 beta (GSK-3β) through phosphorylation (ser9), leading to the accumulation of β-catenin. It was confirmed that the expression of β-catenin phosphorylation, which induces the degradation of β-catenin, decreased. Moreover protein kinase A (PKA) phosphorylation was increased by treatment with chrysoeriol. The resultes suggest that the possibility of chrysoeriol and linarin as agents for hypopigmentation treatment through their upregulation of melanogenesis.