Study on the mechanism of wuzi Jiangtang formula Inhibiting skeletal muscle Insulin resistance based on network pharmacology and experimental verification
Objective To explore the mechanism of Wuzi Jiangtang Formula in inhibiting skeletal muscle insu-lin resistance(IR)through the integration of network pharmacology and experimental methods.Methods Active ingredients and their targets in Wuzi Jiangtang Formula were screened from TCMSP database,HERB database,PubChem database and PharmMapper database.Therapeutic targets related to skeletal muscle IR and autophagy were collected and filtered.GO and KEGG enrichment analysis was performed on the intersec-tion of the three datasets,then both the PPI network and ingredient-target-pathway network model were con structed to identify the core targets,key ingredients,and pathways.Molecular docking was performed by softwares including AutoDockTool,Vina,Pymol,and Chem3D.A diabetic animal model was established by combining high-fat diet and streptozotocin(STZ),and the results of network pharmacological analysis were verified by ELISA,HE staining and Western blot.Results A total of 143 targets related to the inhibition of skeletal muscle IR and autophagy by Wuzi Jiangtang Formula were identified.GO and KEGG enrichment an-alyses revealed that the signaling pathways mainly focused on PI3K-Akt,TNF,and AGE-RAGE pathways,involving biological processes such as glucose and lipid metabolism,inflammation,and autophagy.Molecular docking results showed that all the core components such as quercetin,luteolin,kaempferol,and taxifolin were well docked with key targets including AKT1,TP53,TNF,IL6 and PIK3CG.Animal experiments demonstrated that compared with the model group,Wuzi Jiangtang Formula could reduce the insulin resist-ance index,increase PI3K and AKT protein expression,and decrease TNF-α protein expression.Conclusion This study preliminarily revealed that the main active ingredients in Wuzi Jiangtang Formula were querce-tin,luteolin,kaempferol,and taxifolin,which may improve skeletal muscle IR by mediating the PI3K/Akt signaling pathway to regulate autophagy,providing a basis for its basic research and clinical application.
万方数据
维普
