Yinxie Granules (YXKL) and its flavonoids Quercetin/Kaempferol alleviate psoriasis by blocking STING-NF-κB pathway

Psoriasis is a chronic inflammatory skin disease characterized by immune dysregulation and abnormal blood vessel formation. Current treatments often have limitations, and the precise mechanisms of many traditional remedies remain unclear. The STING (Stimulator of Interferon Genes) pathway is a crucial mediator of innate immunity and inflammation, increasingly implicated in inflammatory diseases. Understanding how compounds modulate STING could offer novel therapeutic avenues for psoriasis, addressing both inflammation and vasculopathy.

Researchers investigated the anti-psoriatic mechanisms of Yinxie Granules (YXKL) using patient samples, IMQ-induced psoriatic mice, zebrafish models, and in vitro assays. The study focused on YXKL's effects on skin inflammation, barrier function, and specific signaling pathways. They aimed to identify the active components within YXKL responsible for its therapeutic effects and characterize their molecular targets. Assays included analysis of macrophage/Th17 infiltration, pro-inflammatory cytokine levels via ELISA, loricrin expression, and STING pathway activation.

YXKL significantly alleviated skin inflammation and restored the skin barrier. This was achieved by reducing M1 macrophage and Th17 infiltration, lowering pro-inflammatory cytokines such as IL-6, IFN-β, IL-23, and IL-17, and increasing loricrin expression. Mechanistically, a dynamic transition in STING signaling was observed during psoriasis progression: both STING/IRF3 and STING/NF-κB pathways were activated in moderate disease, but only STING/NF-κB was hyperactivated in severe psoriasis. YXKL specifically targeted the STING/NF-κB pathway to mitigate inflammation and vasculopathy, without impacting upstream regulators like TRAF6, LKB1, AMPK, or ULK1.

Quercetin and kaempferol were identified as the primary STING-modulating components in YXKL, directly binding to STING proteins and inhibiting downstream pathway activation. These flavonoids suppressed skin inflammation and angiogenesis while enhancing vascular integrity through STING inhibition in both keratinocytes and endothelial cells.