Cycloastragenol reduces inflammation and apoptosis in acute lung injury by inhibiting the NF-κB p65 and Akt pathways.

Abstract

Cycloastragenol, a triterpenoid saponin extracted from Astragalus membranaceus, exerts several pharmacological effects. However, its mechanism of action in acute lung injury treatment remains unclear. This study was conducted to test the hypothesis that cycloastragenol can inhibit lipopolysaccharide (LPS)-induced acute lung injury and investigate the underlying molecular mechanisms. This study systematically explored the effects and mechanism of action of cycloastragenol in LPS-induced acute lung injury treatment using network pharmacology, molecular docking, molecular dynamics simulation, and experimental validation. Gene Ontology and Kyoto Encyclopedia of Gene and Genomes enrichment analyses indicated that the effects of cycloastragenol are mediated by inflammation- and apoptosis-related genes. Both in vitro and in vivo experiments were conducted to assess the effectiveness of cycloastragenol in acute lung injury treatment. Lung function was evaluated using a pulmonary function test system with indicators, such as peak expiratory flow, minute ventilation, and lung resistance. The expression of inflammatory factors and apoptosis-related proteins was evaluated using Western blot analysis, quantitative real-time polymerase chain reaction, and immunofluorescence. Apoptosis in lung tissue and mouse primary peritoneal macrophages was assessed using terminal deoxynucleotidyl transferase dUTP nick-end labelling staining and flow cytometry, respectively. Cycloastragenol effectively alleviated pulmonary dysfunction and edema, mitigated histopathological damage, and suppressed the activation of both the NF-κB p65 and Akt signaling pathways induced by LPS, ultimately leading to reduced inflammation and apoptosis. The results suggest that cycloastragenol alleviates acute lung injury by exerting anti-inflammatory and anti-apoptotic effects. These findings suggest that cycloastragenol could be a potential therapeutic candidate for preventing and treating ALI.