基于网络药理学及实验验证探讨温脾消导方治疗非酒精性脂肪肝病的作用机制OA北大核心CSTPCD

Objective:To study the therapeutic effect of Wenpi Xiaodao Decoction on non-alcoholic fatty liver disease(NAFLD)in rats based on network pharmacology and experimental verification,and the changes of SIRT1-FoxO1-autophagy pathway and its molecular mechanism.Methods:TCMSP,BATMAN-TCM,GeneCards and OMIM databases were used to ob-tain the potential active ingredients and targets of Wenpi Xiaodao Decoction in treating NAFLD.Cytoscape 3.9.1 software and STRING database were used to construct TCM-active ingredient-disease target network and protein protein interaction(PPI)network,and key active ingredients and core targets were screened.GO and KEGG enrichment analysis of intersection targets was performed by R4.2.2 software.NAFLD model was established by feeding SD rats with high-fat diet for 12 weeks.After successful modeling,the rats were intervened with low(7.43 g/kg),medium(14.85 g/kg),high(29.70 g/kg)doses of Wenpi Xiaodao De-coction and polyene phosphatidylcholine capsules for 8 weeks.HE staining,oil red O staining,Western blot and other methods were used to verify the efficacy in vivo and explore the mechanism.Results:The prediction results of network pharmacology showed that Wenpi Xiaodao Decoction may treat NAFLD through key components such as quercetin,Methylheptenone,luteolin,kaempferol and core targets such as STAT3,JUN,MYC,ESR1.KEGG enrichment analysis showed that Wenpi Xiaodao De-coction may treat NAFLD by regulating AGE-RAGE,IL-17,FoxO and TNF signaling pathways.The results of animal experi-ments showed that low,medium and high doses of Wenpi Xiaodao Decoction and polyene phosphatidylcholine could reduce the de-gree of liver steatosis and lipid droplet accumulation in NAFLD rats,significantly reduce the contents of TC,TG,LDL-C,AST and ALT in serum(P<0.05),increase the content of HDL-C(P<0.05),significantly reduce the expression levels of ac-foxo1 and p62 protein in liver(P<0.05),and significantly increase the levels of FoxO1,LC3 Ⅱ/LC3 Ⅰ SIRT1 protein expression lev-el(P<0.05).Conclusion:Wenpi Xiaodao Decoction can significantly improve liver function,blood lipid levels and liver steatosis.Its mechanism may be related to the activation of SIRT1-FoxO1-autophagy pathway.