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

Background Vitiligo is a dermatological disorder characterized by the progressive loss of functional melanocytes, leading to patchy skin depigmentation. The traditional Chinese medicine (TCM) strategy for treating vitiligo is based on the principles of nourishing the liver and kidney, complemented by activating blood circulation to resolve stasis. Qubai Tincture (QBDJ) is a patented TCM formula that has shown clinical promise in vitiligo, but its molecular mechanisms remain unknown. The specific question addressed here is whether QBDJ exerts protective effects through the modulation of metabolic and proteomic pathways. This study used a 2.5% hydroquinone-induced chemical depigmentation mouse model and integrated multi-omics (metabolomics and proteomics) to investigate this hypothesis. Methods Chemical composition of QBDJ was analyzed using ultra performance liquid chromatography combined with quadrupole Orbitrap high resolution mass spectrometry (UHPLC-Q-Orbitrap-HRMS). A chemical depigmentation 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. Results A 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 chemical depigmentation models, versus 287 down-regulated and 256 up-regulated metabolites with 915 down-regulated and 670 up-regulated proteins in QBDJ-treated mice. Integrated multi-omics analysis indicated that QBDJ treatment was associated with the normalization of amino acid, lipid, and nucleotide metabolic profiles and reduced oxidative stress markers, accompanied by evidence of melanocyte recovery in depigmented skin. Conclusions In a chemical depigmentation mouse model, QBDJ administration was associated with potential trends inferred from multi-omics profiling reduced depigmentation and partial normalization of dysregulated metabolic and proteomic profiles. These multi-omics findings suggest that QBDJ may act through multi-component, multi-target mechanisms involving metabolic regulation, and deserves further evaluation as a potential supplementary approach for vitiligo. This study provides a foundation for future investigation of QBDJ and related TCM-based strategies in vitiligo research.