Multi-omics analysis of skin tissue metabolome and proteome reveals the repigment effect of Qubai tincture against vitiligo in mice

Abstract

BackgroundVitiligo is an autoimmune-mediated dermatological disorder characterized by the progressive loss of functional melanocytes, leading to patchy skin depigmentation. The traditional Chinese medicine (TCM) strategy for treating vitiligo centers on nourishing the liver and kidneys, complemented by activating blood circulation to resolve stasis. Qubai Tincture (QBDJ) is a Chinese patent medicine demonstrated clinical efficacy in treating vitiligo, yet its active components and mechanisms of QBDJ remain undetermined, and the reported research is limited.This study aimed to evaluate the protective effect and mechanistic basis of QBDJ against a 2.5% hydroquinone-induced vitiligo through integrated multi-omics (metabolomics and proteomics) analysis.MethodsChemical composition of QBDJ was analyzed using ultra performance liquid chromatography combined with quadrupole Orbitrap high resolution mass spectrometry (UHPLC-Q-Orbitrap-HRMS). A vitiligo mouse model was established with 2.5% hydroquinone. Therapeutic effects were assessed via skin observation, histopathology, and biomarkers (inflammatory cytokines, α-MSH, TyR, SOD). Untargeted metabolomics and Data-Independent Acquisition (DIA) proteomics were used to reveal the mechanism of QBDJ intervention in vitiligo.ResultsA total of 49 bioactive components, mainly flavonoids and anthracenes, were identified. With each dose of QBDJ, the skin color of mice became darker, the melanin content increased, the lesion site returned to normal, and the expression level of corresponding indicators decreased. Multi-omics profiling revealed 280 down-regulated and 256 up-regulated metabolites with 876 down-regulated and 1654 up-regulated proteins in vitiligo models, versus 287 down-regulated and 256 up-regulated metabolites with 915 down-regulated and 670 up-regulated proteins in QBDJ-treated mice. Integrated analysis revealed that QBDJ counteracts vitiligo by rectifying disruptions in amino acid, lipid, and nucleotide metabolism, mitigating oxidative stress, and thereby promoting melanocyte regeneration.ConclusionsQBDJ treats vitiligo through multiple components and multi-target mechanisms, primarily by correcting metabolic disturbances. This study offers a scientific basis for its clinical application and guides TCM treatment of vitiligo.