Background A phytochemical 5-demethylnobiletin from Citrus reticulata Blanco has a broad spectrum of pharmacological effects on anti-inflammatory, cardiovascular and neuroprotective effects, however, its in vivo effect on depigmentation remains unknown. Objective To investigate how 5-demethylnobiletin regulates melanogenesis, both in vitro and in vivo experiments were conducted to evaluate its efficacy and mechanisms in human epidermal melanocyte and mice model of chemical-induced vitiligo. Methods C57BL/6 mice were induced with 1% hydroquinone (HQ) to shaved dorsal skin and applied with 5-demethylnobiletin or 8-methoxypsoralen (8-MOP, positive control). Melanin contents measurement, immunohistochemistry, Fontana-Masson and HE histological analysis were used to determine melanin contents in follicles. q-PCR, Western blot, dichlorofluorescein (DCF) assay and computational docking were adopted to investigate the molecular mechanisms of 5-demethylnobiletin in the vitiligo mice model. Besides, acute dermal irritation test was conducted to evaluate the biological safety of 5-demethylnobiletin in mice. Results 5-demethylnobiletin possessed in vitro anti-oxidative effect, significantly increased melanin...

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