Mechanistic insights into the amelioration effects of lipopolysaccharide-induced acute lung injury by baicalein: An integrated systems pharmacology study and experimental validation

Abstract

BackgroundAcute lung injury is an acute progressive respiratory failure caused by several of non-cardiogenic factors which involves in excessive amplification or uncontrolled inflammatory response. ObjectivesIn this study, we investigated the protective effect of baicalein against acute lung injury induced by LPS and explored the underlying mechanisms. MethodsForty-eight SPF male C57BL/6 mice were randomly divided into normal group, model group, dexamethasone group and baicalein low-dose, medium-dose and high-dose groups. After 5 days of adaptive feeding, the mice were intraperitoneally injected with LPS and dissected after 12 h. Hematoxylin-eosin staining, ELISA assay, immunofluorescence assay and Western-Blot were applied to appraise microstructural changes and protein expressions of lung tissues. Systems pharmacology study was used to evaluate the protection of baicalein on acute lung injury. FindingsThe results showed that baicalein administration could significantly inhibit LPS-induced lung morphological changes, inhibit inflammatory response and pyroptosis. A total of forty-three potential targets of baicalein and acute lung injury were obtained. And PI3K-Akt, TNF and NF-κB were mainly signaling pathways. It is worth mentioning that this experiment also confirmed that NLRP3, caspase-1 and other inflammasome are involved in pyroptosis. ConclusionBaicalein has protected against LPS-induced lung tissues injury via inhibiting inflammatory response and pyroptosis.