Yubai Wan ameliorates vitiligo by inhibiting ferroptosis via NRF2/GPX4 pathway.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Tribulus terrestris L was explicitly recorded as a treatment for vitiligo in the Compendium of Materia Medica. Yubai Wan, a hospital-prepared formulation composed of Tribulus terrestris L. and honey, has been widely administered to patients with vitiligo. However, its bioactive constituents and underlying mechanisms remain insufficiently elucidated. AIM OF THE STUDY: This study evaluates the active ingredients of Yubai Wan for vitiligo and explores its mechanisms. MATERIALS AND METHODS: First, metabolomic, transcriptomic, and clinical analyses were performed to identify the active components of Yubai Wan and to elucidate the mechanisms of vitiligo. The B16 cells were triggered ferroptosis with hydroquinone. In addition, a hydroquinone-induced guinea pig model of vitiligo was established and treated with quercetin. Ferroptosis-related markers were evaluated through histological analysis, western blot and quantitative PCR. Finally, ferroptosis-related indicators were assessed after treatment with ML385 and quercetin in B16 cells. RESULTS: In this study, quercetin was identified as an active component of Yubai Wan. Clinically, ferroptosis scores and total iron levels were significantly elevated in patients with vitiligo. In vitro, a dose of hydroquinone markedly induced ferroptosis in B16 cells. In vivo, quercetin alleviated vitiligo-like symptoms in guinea pigs and attenuated ferroptosis in their skin tissues. Notably, quercetin significantly upregulated the protein (mRNA) expression levels of NRF2 (Nfe2l2) and GPX4 (Gpx4). The therapeutic effects of quercetin were further verified in B16 cells. Furthermore, inhibition of NRF2 (Nfe2l2) partially abrogated the protective effects of quercetin against hydroquinone-induced ferroptosis in B16 cells. CONCLUSION: This study reveals quercetin, as the main component of Yubai Wan, exerts anti-ferroptosis on vitiligo through activating the NRF2/GPX4 signaling pathway.