Network Pharmacology And Experimental Study Of Buyang Huanwu Decoction On The Treatment Of Type 2 Diabetes Mellitus With Fatty Liver Disease

Background: This research aims to reveal the effect of Buyang huanwu decoction(BHD)on diabetic fatty liver,by using network pharmacology methods to research and verify through animal experiments and cell experiments.Methods: The drug components were collected by tcmsp database and target prediction through swisstarget website,the relevant targets of the disease were obtained by using the database of digenet 6.0,drugbank and HPO,KEGG pathway and GO biological process were analyzed by David 6.8,key targets were analyzed by string database;The rats were grouped into normal group(Nor),model group(Mod),metformin group(Met)and Buyang Huanwu Decoction group(BHD),the levels of Glu,TG,TC,AST and ALT were detected,the weight of liver tissue was measured and compared with the body weight of animals,the pathological changes of rat liver were observed by paraffin section and he staining,the protein level of liver was detected by Western blot;In cell experiment,oleic acid induced Hep G2 cell steatosis,the levels of TG and lipid deposition were detected by oil red staining,western blot was used to test the protein level.Results: Network pharmacology analysis showed that there were 68 targets,which were obtained through the intersection of Buyang Huanwu Decoction and diabetic fatty liver,the biological process is related to the kinase,inflammatory factor,apoptosis and substance metabolism,its action pathway is related to PPAR signaling pathway,PI3K-Akt signaling pathway,HIF-1 signaling pathway,FOXO signaling pathway and AMPK signaling pathway,The key targets are AKT1,TNF,PPARG,etc,the compounds related to AKT1 were quercetin,kaempferol,luteolin,baicalein and other flavonoids.Animal experiments showed that BHD group compare with the model group,BHD significantly reduced the ast level of diabetic rats(P < 0.01),decreased the levels of Glu,TC,TG and ALT(P < 0.05),and alleviated the fatty lesion of liver tissue,model group compare with the normal group,the expressions of PI3 K,beclin-1 and Akt down in the liver,while the expressions of Caspase-3,NF-κB and AGER up in the liver,compared with the model,the expression of PI3 K,Akt and beclin-1 increased,while the expression of Caspase-3,NF-κB and AGER decreased.In the cell,model compare with normal,TG level increased significantly(P < 0.01),lipid deposition increased,PI3 K and Akt expression decreased,but Caspase-3 and NF-κB expression increased,the serum containing Buyang Huanwu Decoction and kaempferol decreased the level of TG(P < 0.05),decreased the effect of lipid deposition,increased the expression of PI3 K and Akt,decreased the expression of Caspase-3 and NF-κB.Conclusion: BHD can regulate autophagy,apoptosis and inflammation,regulate PI3K-Akt signaling pathway,and has therapeutic effect on diabetic fatty liver.