Résumé
Acute lung injury is a severe disease with a high mortality rate, which can result in increased oxidative stress and further mitochondrial damage and cell apoptosis. L-Clausenamide is an amide from the fruit wampee. This study combined network pharmacology, molecular docking, and in vitro study to elucidate the effect of combating acute lung injury and the underlying mechanism of L-Clausenamide. Network pharmacology indicated that the 152 targets can treat acute lung injury through regulating oxidative stress. Based on PPI analysis and screening of the central target, AKT1 is the key target of the underlying mechanism. KEGG and GO enrichment analysis demonstrated that apoptosis is an important pathway for this curing effect. In the in vitro study, treatment with L-Clausenamide alleviates intracellular ROS accumulation, mitochondrial membrane potential loss, mitochondrial morphological distortion, ATP decrease, and the CASP3 activity. The SPR analysis was performed to validate the binding between AKT1 and L-Clausenamide. The Western blot result showed that L-Clausenamide increases the phosphorylation of Akt and decreases cleavage of CASP3. L-Clausenamide can alleviate lipopolysaccharide (LPS)-induced acute lung injury through targeting AKT1 and show an improvement in mitochondrial abnormality and inhibition against ROS-activated caspase-3-dependent apoptosis activation.