Fufang Baizhi tincture protects melanocytes from oxidative stress by targeting CASP7-mediated apoptosis and EP300-associated transcriptional regulation.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Baizhi Tincture (FFBZD) is a traditional topical Chinese medicine. This study demonstrates that FFBZD regulates melanocytes by modulating apoptosis via Caspase 7 (CASP7) and transcriptional regulation via E1A-associated protein p300 (EP300), thereby influencing vitiligo. These findings further links its traditional use with specific genetic targets and mechanism-based preventive and therapeutic potential.

AIM OF THE STUDY: Although traditionally used for the management of vitiligo, the mechanisms of FFBZD remain unclear, and this study aims to elucidate its therapeutic targets and molecular pathways.

METHODS

We employed an integrated strategy combining network pharmacology with Mendelian Randomization (MR) to identify and causally prioritize FFBZD's targets in vitiligo. By integrating large-scale Genome-Wide Association Study (GWAS) data with multi-tissue expression Quantitative Trait Loci (eQTL) and protein Quantitative Trait Loci (pQTL) data, we performed summary-data-based MR (SMR) and colocalization analyses. Key computational predictions were then validated in a hydrogen peroxide (H2O2)-induced oxidative stress model in human melanocytes.

RESULTS

Our genetic analysis prioritized 34 candidate genes from 465 potential targets. A potential association was identified between increased CASP7 expression and higher vitiligo risk across blood and skin tissues (OR = 1.2, PPH4>0.5). We demonstrated that FFBZD tincture potently protected melanocytes from H2O2-induced apoptosis and restored melanogenesis. Mechanistically, FFBZD treatment suppressed the expression of the pro-apoptotic gene CASP7 and rescued the expression of the transcriptional coactivator EP300. Importantly, these protective effects were validated by pharmacological rescue experiments using specific modulators. Molecular docking further implicated Pinocembrin, a key FFBZD compound, as a potential modulator of CASP7.

CONCLUSION

This study elucidates the potential mechanism of a traditional therapy for vitiligo and identifies CASP7 and EP300 as potential key targets. Fufang Baizhi Tincture likely exerts its protective effects by modulating these targets to regulate melanocyte apoptosis and transcription, providing a robust scientific basis for its clinical application.