EXPLORATION OF THE FUNCTION OF GINSENOSIDE RD ATTENUATES LIPOPOLYSACCHARIDE-INDUCED LUNG INJURY: A STUDY OF NETWORK PHARMACOLOGY AND EXPERIMENTAL VALIDATION

摘要

ABSTRACT—Objective: Ginsenoside Rd (GSRd) displays a variety of pharmacological effects. However, the underlying role in acute lung injury (ALI) is not clear. In this study, the protective effect of GSRd on lipopolysaccharide (LPS)-induced ALI is investigated to explore the potential mechanisms. Methods: GSRd-target-ALI-related gene set was constructed. And bioinformatics tools were used to discover the potential mechanism. We observed the survival of subjects for 72 h. In addition, male BALB/c mice were intraperitoneal injected with GSRd (25 and 50mg/kg) after received one intratracheal instillation of LPS. Inflammatory changes, oxidative stress, and phosphorylation were assessed to study the biological effects. Results: A total of 245 interaction genes were collected. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were enriched in immune-inflammatory system. Among them, PI3K-Akt signaling pathway was the highest-ranked pathway of inflammatory response. In vivo study, it was found that GSRd improved survival in endotoxemic mice and inhibited the major characteristic of ALI. And the p-PI3K and p-Akt expression was significantly decreased by GSRd treatment. Conclusion: GSRd could protect mice against LPS-induced ALI effectively by inhibiting the PI3K-Akt signaling pathway.