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

  • Author Footnotes
    1 Authors contributed equally.
    Ting Fu
    Footnotes
    1 Authors contributed equally.
    Affiliations
    Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China
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  • Author Footnotes
    1 Authors contributed equally.
    Xiaofeng Qin
    Footnotes
    1 Authors contributed equally.
    Affiliations
    Department of Dermatology, Changhai Hospital of Shanghai, Second Military Medical University, Shanghai, China
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  • Author Footnotes
    1 Authors contributed equally.
    Yining Ma
    Footnotes
    1 Authors contributed equally.
    Affiliations
    Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China
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  • Author Footnotes
    1 Authors contributed equally.
    Xinyue Yuan
    Footnotes
    1 Authors contributed equally.
    Affiliations
    Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China
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  • Siyun Wu
    Affiliations
    Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China
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  • Xiyun Ye
    Correspondence
    Corresponding authors.
    Affiliations
    Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China
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  • Yongyan Dang
    Correspondence
    Corresponding authors.
    Affiliations
    Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China
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  • Author Footnotes
    1 Authors contributed equally.

      Highlights

      • 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

      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/β-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 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.

      Conclusions

      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.

      Keywords

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