Agerarin inhibits α-MSH–induced TYR gene transcription via STAT3 suppression independent of CREB-MITF pathway

Skin pigmentation occurs through melanogenesis in melanocytes [1]. Melanin synthesis is regulated by many enzymes, including tyrosinase [2], TYR-related protein 1 (TRP-1), and TRP-2, located in melanosomes [3]. TYR is a rate-limiting enzyme that converts tyrosine to 3,4-hydroxyphenylalanine (DOPA) and oxidize DOPA to DOPA quinone, leading to the progression of melanin formation [4]. Melanocyte-stimulating hormone (α-MSH) is a tridecapeptide derived from pro-opiomelanocortin. In the skin, α-MSH is produced from keratinocytes in response to solar ultraviolet radiation [5] and stimulates melanocortin-1 receptor (MC1R) on the melanocytes.