Journal of Functional Foods (Jan 2024)
Melanogenic effects of 5-demethylnobiletin on mouse model of chemical-induced vitiligo
Abstract
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 content in hair and ameliorated hypopigmentation in mice. The expression level of melanogenesis-related genes such as MITF, tyrosinase, Trp-1 and Trp-2 were significantly upregulated in 5-demethylnobiletin-treated groups. Molecular docking results support that 5-demethylnobiletin is able to bind to tyrosinase, the key enzyme for regulating melanogenesis, suggesting the potential molecular target of 5-demethylnobiletin. Conclusions: 5-demethylnobiletin has potential therapeutic effect on delaying the onset of depigmentation in vivo, lessened depigmentation incidence which contributes to melanogenesis. The newly revealed biological activity indicates 5-demethylnobiletin may be a potential natural pharmaceutical for the treatment and prevention of chemical-induced depigmentation disorders, and as the components for anti-gray hair products.
