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Skin hyperpigmentation is mainly caused by excessive synthesis of melanin; however, there is still no safe and effective therapy for its removal. Here, we found that the dermal freezer was able to improve UVB‐induced hyperpigmentation of guinea pigs without causing obvious epidermal damage. We also mimic freezing stimulation at the cellular level by rapid freezing and observed that freezing treatments <2.5 min could not decrease cell viability or induce cell apoptosis in B16F10 and Melan‐A cells. Critically, melanin content and tyrosinase activity in two cells were greatly reduced after freezing treatments. The dramatic decrease in tyrosinase activity was associated with the downregulation of MITF, TYR, TRP‐1 and TRP‐2 protein expression in response to freezing treatments for two cells. Furthermore, our results first demonstrated that freezing treatments significantly reduced the levels of p‐GSK3β and β‐catenin and the nuclear accumulation of β‐catenin in B16F10 and Melan‐A cells. Together, these data suggest that fast freezing treatments can inhibit melanogenesis‐related gene expression in melanocytes by regulating the Wnt/β‐catenin signalling pathway. The inhibition of melanin production eventually contributed to the improvement in skin hyperpigmentation induced by UVB. Therefore, fast freezing treatments may be a new alternative of skin whitening in the clinic in the future. [ABSTRACT FROM AUTHOR]

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. The aim of the study is to investigate the anti-melanogenic function of yohimbine hydrochloride and reveal its underlying molecular mechanism. 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/β-catenin and p38/MAPK signal pathways were determined by RT-qPCR, Western blot analysis and immunofluorescent staining. 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 downregulated after YH treatments along with the reduction of tyrosinase activity. YH markedly inhibited β-catenin nuclear accumulation and p38 phosphorylation in B16F10 cells compared with the untreated controls. Importantly, the increase of MITF expression induced by β-catenin activator BIO and p38 activator anisomycin could be fully reversed by YH treatments. These results indicate that YH can function as an anti-melanogenic agent, at least in part, by inhibiting Wnt/β-catenin and p38/MAPK signal pathways. Therefore, YH may be potentially used as a skin-whitening compound for preventing hyperpigmentation disorders in the future. • This manuscript extends the novel function of YH as the anti-melanogenic agents. • It is first to report YH could inhibit β-catenin nuclear accumulation and p38 phosphorylation. • YH downregulates MITF expression via regulating Wnt/β-catenin and p38/MAPK signal pathways. [ABSTRACT FROM AUTHOR]