SAAS attenuates LPS-induced acute lung injury by targeting HMGB1-mediated NF-κB/NLRP3 inflammasome signaling.

BACKGROUND: Acute lung injury (ALI) induced by lipopolysaccharide (LPS) involves severe inflammation and epithelial damage, necessitating effective therapeutic strategies. This study investigated the protective effects and mechanisms of salvianic acid A sodium (SAAS) against LPS-induced cytotoxicity and ALI. METHODS: efficacy was evaluated in an LPS-induced murine ALI model treated with SAAS via histopathology, lung wet/dry weight ratio, myeloperoxidase (MPO) activity, serum/lung cytokine levels (ELISA), and immunohistochemistry (IHC). Mechanistic insights were gained through western blot and qPCR analysis of HMGB1 signaling components. In the ALI model, SAAS administration ameliorated histopathological damage, attenuated pulmonary edema, suppressed MPO activity, and reduced systemic and pulmonary levels of TNF-α, IL-6, IL-18, and IL-1β. Mechanistically, SAAS inhibited LPS-induced HMGB1 upregulation, acetylation, and nuclear-to-cytoplasmic translocation. Consequently, it suppressed downstream NF-κB activation and NLRP3 inflammasome assembly/activation. CONCLUSION: SAAS confers significant protection against LPS-induced ALI by targeting the HMGB1 signaling axis. It inhibits HMGB1 expression, acetylation, and cytoplasmic translocation, thereby disrupting NF-κB-mediated cytokine production and NLRP3 inflammasome activation. These findings identify SAAS as a promising multi-target therapeutic agent for inflammatory lung injury.