Kang, Min-Sung Jang, Sung-Chan Park, Taejin Kim, MinSeon Park, Jin-Soo Chi, Won-Jae Kim, Seung-Young 2024-01-12T03:32:36Z 2024-01-12T03:32:36Z 2022-03-08 2022-02 1934-578X https://pubs.kist.re.kr/handle/201004/76799 Tyrosinase ultimately controls the melanogenesis rate of the skin, and tanning and haircare products generally induce the activation of tyrosinase. Moreover, various enzymes, including tyrosinase, tyrosinase-related protein 1 (TRP1), and tyrosinase-related protein 2 (TRP2), mediate melanogenesis in which microphthalmia-associated transcription factor (MITF) is a master regulator. One coumarin family member 7,8-dihydroxy-4-methylcoumarin (DHMC) shows extensive biological activities with beneficial health effects; however, it also induces cytotoxicity and its melanogenic effect has not been reported yet. Therefore, we first synthesized DHMC derivatives via methylation to obtain 7,8-dimethoxy-4-methylcoumairn (DMMC), and investigated the pro- or anti-melanogenic effects of DHMC and DMMC in B16-F10 melanoma cells as well as the underlying mechanism. DHMC showed cytotoxicity at all tested concentrations, whereas DMMC did not reduce cell viability, even at the high concentration. DMMC also drives the significant increase in intracellular melanin and tyrosinase activity. Moreover, DMMC induced MITF expression by significantly increasing tyrosinase activity, which activates the gene expression of TRP1 and TRP2. Western blotting confirmed that DMMC induced the activation of mitogen-activated protein kinase (MAPK) signaling by the phosphorylation of C-Jun N-terminal kinase (JNK), resulting in the increased melanin production and the decreased phosphorylation of protein kinase B. Collectively, this study showed the pro-melanogenic effect of DMMC and its potential as a safe tanning and dyeing agent. English SAGE PUBLICATIONS INC Synthesis and Melanogenesis Effect of 7,8-Dimethoxy-4-Methylcoumarin via MAPK Signaling-Mediated Microphthalmia-Associated Transcription Factor Upregulation Article 10.1177/1934578x221076647 1 NATURAL PRODUCT COMMUNICATIONS, v.17, no.2 NATURAL PRODUCT COMMUNICATIONS 17 2 N scie scopus 000765272400001 2-s2.0-85125858748 Chemistry, Medicinal Food Science & Technology Pharmacology & Pharmacy Food Science & Technology COUMARIN DERIVATIVES MELANIN SYNTHESIS INHIBITION TYROSINASE ACTIVATION CHEMISTRY EXTRACT PATHWAY CELLS COLOR methylation 7 8-dihydroxy-4-methylcoumarin 7 8-dimethoxy-4-methylcoumairn melanogenesis B16-F10 melanoma cell MAPK pathway coumarin