摘要Psoriasis is a chronic skin disease driven by skin inflammation and abnormal subcutaneous blood vessels.Yinxie Granules(YXKL)is a clinically effective traditional Chinese medicine(TCM)formula that has shown promise in psoriasis treatment,but its pharmacological mech-anisms and material basis remain unclear,limiting its clinical application and co-administra-tion with other drugs.In this study,we explored the mechanism and active components of YXKL in the treatment of psoriasis using patient samples,IMQ-induced psoriatic mice,zebrafish,and in vitro assays.We discovered that YXKL alleviated skin inflammation and re-stored the skin barrier by reducing M1 macrophage/Th17 infiltration,lowering pro-inflam-matory cytokines(IL-6,IFN-β,IL-23,IL-17),and increasing loricrin expression.Mechanistic-ally,we identified a dynamic transition in STING signaling during psoriasis progression.Both the STING/IRF3 and STING/NF-κB pathways were activated in moderate psoriasis,while only the STING/NF-κB pathway was hyperactivated in severe disease.YXKL specifically targeted the STING/NF-κB pathway to mitigate inflammation and vasculopathy but had no significant impact on the upstream regulators,including TRAF6,LKB1,AMPK,and ULK1.Quercetin and kaempferol were identified as the primary STING-modulating components in YXKL,binding to STING proteins and inhibiting downstream pathway activation.These flavonoid components mediate the anti-psoriatic effects of YXKL by simultaneously suppressing skin inflammation and angiogenesis while enhancing vascular integrity through STING inhibition in both kerat-inocytes and endothelial cells.Our results elucidated the molecular basis of YXKL for psorias-is treatment,highlighting STING/NF-κB as a pivotal therapeutic target in mitigating psoriasis development and providing natural candidate compounds as potential STING inhibitors.