Isorhamnetin protects melanocytes against CD8+ T cell-mediated apoptosis and reduces inflammation in vitiligo-afflicted mouse

CD8 + T cells significantly reduced melanocyte viability and increased apoptosis. However, ISO pretreatment improved cell viability and reduced apoptosis. ISO also downregulated proinflammatory cytokines (TNF-α, IFN-γ, IL-6, and IL-8) and chemokines (CXCL9 and CXCL10), as well as p53 and Bcl-2 expression at protein levels in vitiligo mouse models. RNA sequencing identified and molecular docking suggested key differentially expressed genes (PTK7, DLL1, IL21R, and CD226) as potential targets for treatment. KEGG analysis indicated that ISO plays a protective role through the Notch signaling pathway. Further functional experiments suggested that inhibition of PTK7/DLL1 and Notch signals reversed the apoptosis-protective effect of ISO on melanocytes, emphasizing its potential as a therapeutic option for vitiligo treatment.