Network pharmacology and molecular docking study on the effect of Kaempferol in treatment of metabolic associated fatty liver disease.

objectiveTo study therapeutic effect of kaempferol on metabolic associated fatty liver disease (MAFLD) by network pharmacology and molecular docking combined with cell experiments.

methodsFirst, use the SwissTargetPrediction database to predict the targets of kaempferol, and collect the targets of MAFLD through the Disgenet database and the GeneCards database. Then, the common target of kaempferol and MAFLD was enriched and analyzed by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes, and the protein-protein interaction (PPI) network was constructed through the string database to obtain the key targets, and carry out molecular docking of key targets with kaempferol; In cell experiment, oleic acid induced steatosis in HepG2 cells, which was intervened by kaempferol, the level of triglyceride (TG) was detected, the lipid deposition was observed by oil red O staining, and the protein expression was detected by Western blot.

resultsThe results showed that there are 33 common targets for kaempferol and MAFLD. The biological process of GO is related to the regulation of protein kinase B, cell apoptosis, inflammatory factors, lipoxygenase, etc. Its action pathway is related to the phosphatidylinositol-3-kinase and protein kinase B (PI3K-AKT) signaling pathway, hypoxia-inducible factor 1 signaling pathway, forkhead box protein O signaling pathway, AMP-activated protein kinase signaling pathway, tumor necrosis factor signaling pathway, etc., the key targets are protein kinase B (AKT1), pros-taglandin G/H synthase 2, matrix metalloproteinase-9, epidermal growth factor receptor, and the molecular docking of kaempferol with the four key targets shows good binding properties. Cell experiments show that kaempferol can reduce cell TG levels, reduce lipid deposition, increase the expression of PI3K, AKT, and beclin-1, and reduce the expression of caspase-3 and nuclear factor-kappa B. Kaempferol can treat MAFLD by regulating the PI3K-AKT signaling pathway to regulate cell autophagy, apoptosis, and inflammation.

conclusionsThis study shows that kaempferol can regulate lipid metabolism, reduce apoptosis, regulate inflammation and autophagy in the fatty liver cell model. It reveals the therapeutic mechanism of kaempferol on MAFLD and provides a natural product candidate for the treatment of MAFLD.