Cirsium japonicum leaf extract attenuated lipopolysaccharide-induced acute respiratory distress syndrome in mice via suppression of the NLRP3 and HIF1α pathways.

Summary

In an LPS-induced murine ARDS model, Cirsium japonicum extract reduced histopathologic lung injury and dampened macrophage-driven inflammation. Mechanistically, it suppressed NLRP3 inflammasome and HIF1α-associated glycolytic programs in vivo and in MH-S/BMDM in vitro, suggesting macrophage immunometabolic targeting as a therapeutic avenue.

Key Findings

• Cirsium japonicum extract reduced alveolar wall thickening, inflammatory cell infiltration, proteinaceous debris, and hyaline membrane formation in LPS-induced ARDS lungs.
• It decreased inflammatory cell influx and pro-inflammatory gene expression in bronchoalveolar lavage fluid, mitigating alveolar macrophage activation and neutrophil chemoattraction.
• It suppressed NLRP3 and HIF1α expression in vivo and reduced LPS-induced inflammasome- and glycolysis-associated genes in MH-S cells and bone marrow-derived macrophages.

Clinical Implications

While preclinical, findings prioritize macrophage-targeted anti-inflammatory strategies and motivate development of agents that suppress NLRP3/HIF1α axes for ARDS.

Limitations

• Preclinical mouse LPS model may not fully recapitulate human ARDS heterogeneity.
• Active constituents, dosing, pharmacokinetics, and safety in large animals/humans remain undefined.

Future Directions

Isolate and characterize active compounds, define PK/PD, test in polymicrobial/viral ARDS and large-animal models, and evaluate safety in early-phase clinical trials.