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

Authors

Zhiyu Xie, Chong Liu, Xianhui Hong, Jianwei Shen

Published in

Histology and histopathology. Pages 25124. Jul 14, 2026. Epub Jul 14, 2026.

Abstract

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.
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.
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.
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.

PMID:
42444471
Bibliographic data and abstract were imported from PubMed on 14 Jul 2026.

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