Demethyleugenol β-Glucopyranoside Isolated from Agastache rugosa Decreases Melanin Synthesis via Down-regulation of MITF and SOX9.
Agastache rugosa (Fisch. & C. A. Mey.) Kuntze has been well-known for its antioxidative properties. This study investigated the anti-melanogenesis effect of demethyleugenol β-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.
College of Pharmacy, Yonsei University , 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Republic of Korea.
Taek Hwan
TH
Lee
College of Pharmacy, Yonsei University , 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Republic of Korea.
SeonJu
S
Park
College of Pharmacy, Yonsei University , 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Republic of Korea.
Guijae
G
Yoo
Laboratory of Pharmacognosy, College of Pharmacy, Gachon University , 191 Hambakmoero, Yeonsu-gu, Incheon 21936, Republic of Korea.
Cheongyun
C
Jang
Laboratory of Pharmacognosy, College of Pharmacy, Gachon University , 191 Hambakmoero, Yeonsu-gu, Incheon 21936, Republic of Korea.|Gachon Institute of Pharmaceutical Science, Gachon University , 191 Hambakmoero, Yeonsu-gu, Incheon 21936, Republic of Korea.
Mi-Hyun
MH
Kim
College of Pharmacy, Yonsei University , 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Republic of Korea.
Seung Hyun
SH
Kim
Laboratory of Pharmacognosy, College of Pharmacy, Gachon University , 191 Hambakmoero, Yeonsu-gu, Incheon 21936, Republic of Korea.|Gachon Medical Research Institute, Gil Medical Center , Incheon 21565, Republic of Korea.|Gachon Institute of Pharmaceutical Science, Gachon University , 191 Hambakmoero, Yeonsu-gu, Incheon 21936, Republic of Korea.
Sun Yeou
SY
Kim
NHEM; SOX9; demethyleugenol β-glucopyranoside; melanogenesis; reconstructed skin