Yohimbine hydrochloride inhibits skin melanin synthesis by regulating wnt/β-catenin and p38/MAPK signal pathways

Background: Yohimbine hydrochloride (YH) is a prescription drug to treat erectile dysfunction. It also had potential in fighting high blood pressure and diabetic neuropathy as well as promoting weight loss. Objective: The aim of the study is to investigate the anti-melanogenic function of yohimbine hydrochloride and reveal its underlying molecular mechanism. Methods: B16F10 mouse melanoma cells, Melan-A murine melanocyte, Zebrafish embryos and C57BL/6 mouse ear skins were treated with different concentrations of YH. The extracellular and cellular melanin content was detected by spectrometry. The expression of microphthalmia-associated transcription factor (MITF), tyrosinase and the activities of Wnt/beta-catenin and p38/MAPK signal pathways were determined by RT-qPCR, Western blot analysis and immunofluorescent staining. Results: Melanin production could be effectively inhibited by YH at the safe concentration in vitro and in vivo. Q-PCR and WB results showed that the expression of MITF and tyrosinase were strongly down -regulated after YH treatments along with the reduction of tyrosinase activity. YH markedly inhibited beta-catenin nuclear accumulation and p38 phosphorylation in B16F10 cells compared with the untreated controls. Importantly, the increase of MITF expression induced by beta-catenin activator BIO and p38 activator anisomycin could be fully reversed by YH treatments. Conclusions: These results indicate that YH can function as an anti-melanogenic agent, at least in part, by inhibiting Wnt/beta-catenin and p38/MAPK signal pathways. Therefore, YH may be potentially used as a skin -whitening compound for preventing hyperpigmentation disorders in the future. (c) 2022 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.