Demethyleugenol beta-Glucopyranoside Isolated from Agastache rugosa Decreases Melanin Synthesis via Down-regulation of MITF and SOX9

Abstract

Agastache rugosa (Fisch & C. A. Mey.) Kuntze has been well-known for its antioxidative properties. This study investigated the anti-melanogenesis effect of demethyleugenol beta-D-glucopyranoside (1) from A. rugosa by studying molecular regulation of melanogenesis in melan-a mouse melanocytes and normal human epidermal melanocytes (NHEMs) and, in in vivo. models. The SRY (sex-determining region on the Y chromosome)-related high-mobility group (HMG) box 9 (SOX9), one of the critical factors that affect skin pigmentation, is up-regulated. Interestingly, 1 down-regulated the expression of SOX9 and microphthalmia-associated transcription factor (MITF). Reduction of these two transcription factors resulted in a decrease in-melanogenic enzymes such as tyrosinase, tyrosinase-related protein 1, and dopachrome tautomerase. As a result, 1 significantly inhibited melanin synthesis in melan-a mouse melanocytes and NHEMs. In addition, the anti-melanogenic effect of 1 was confirmed in zebrafish and reconstructed skin tissue models. In conclusion, 1, as a potent SOX9 regulator, ameliorates skin pigmentation.