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Updated: Jul 15, 2026
Inducing Acute Lung Injury in Mice by Direct Intratracheal Lipopolysaccharide Instillation
Published on: July 6, 2019
SAAS attenuates LPS-induced acute lung injury by targeting HMGB1-mediated NF-κB/NLRP3 inflammasome signaling
Zhiyu Xie1, Chong Liu1, Xianhui Hong1
1Department of Pediatrics, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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:
In vitro cytoprotection and anti-inflammatory effects of SAAS (0-60 μM) were assessed in LPS-challenged alveolar type II (AT2) epithelial cells using CCK-8 assays and quantification of inflammatory mediators (NLRP3, ASC, IL-1β, IL-6, TNF-α). In vivo 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.
Results:
SAAS (≤60 μM) exhibited no intrinsic cytotoxicity but dose-dependently attenuated LPS-induced AT2 cell death. It significantly suppressed LPS-triggered expression of NLRP3 inflammasome components (NLRP3, ASC), caspase-1, and pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) in vitro. 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.
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