Objective In order to explore the mechanism of Yitangkang in ameliorating(diabetic kidney disease,DKD),we use the technology of metabolomics and network pharmacology.Methods Sixty-four male wistar rats were divided into blank group,model group,YTK group and losartan group(LST)with 16 rats in each group.After the DKD rat model was reproduced and established,YTK and LST granules were continuously garaged for 8 weeks.Fasting blood glucose(FBG),triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)were detected,and renal pathological changes were observed by HE staining.Ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS)was used to analyze the changes of metabolic profile of rats in each group,and the related metabolic pathways were queried with the help of metabo analyst database.The key target of YTK in treating DKD and KEGG enrichment analysis were obtained by using network pharmacology,and a"metabolite-reaction-enzyme-gene"network was constructed.Results YTK can significantly improve the level of FBG,TC,TG,HDL-C,LDL-C and renal tissue morphology in DKD rats.Metabolomics initially screened out 16 metabolites closely related to YTK in the treatment of DKD,mainly involving vitamin B6 metabolism,arachidonic acid metabolism and other metabolic pathways.The results of network pharmacology demonstrate that the core components of YTK in the treatment DKD are quercetin,kaempferol,luteolin,etc.,which mainly involve AKT1,TP53,JUN,STAT3 and other target proteins,closely related to cancer signaling pathway,lipid and atherosclerosis pathway.The combined results of metabolomics and network pharmacology demonstrate that both of them involve arachidonic acid metabolic pathway.Conclusion YTK has a significant efficacy in the treatment of DKD.Metabolomics and network pharmacology analysis demonstrate its mechanism may be that quercetin,kaempferol and luteolin in YTK enhance the influence on arachidonic acid metabolic pathway by regulating various metabolites,which provides a basis for further prevention and treatment of DKD.
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