中药药理与临床2025,Vol.41Issue(2):8-15,8.
茵陈公英汤通过IRS/AKT/FoxO1和TLR4/NF-κB信号通路改善非酒精性脂肪肝病
Yinchen Gongying Decoction(茵陈公英汤)Ameliorates NAFLD via IRS/AKT/FoxO1 and TLR4/NF-κB Signaling Pathways
摘要
Abstract
Objective:To investigate the effect and mechanism of Yinchen Gongying Decoction(茵陈公英汤)in treating non-alcoholic fatty liver disease(NAFLD)based on network pharmacology.Methods:Network pharmacology was employed to predict the common genes shared by Yinchen Gongying Decoction and NAFLD,and gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrich-ment analyses were carried out for these genes.Cytoscape was used to establish the"absorbed components of Yinchen Gongying Decoction-target-pathway"network for revealing the mechanism of Yinchen Gongying Decoction in treating NAFLD.Subsequently,a mouse model of NAFLD was established with a 60%high-fat diet,and mice were randomized into normal,model,pioglitazone hydrochloride(0.002 g/kg),and Yinchen Gongying Decoction(1.5,3.0,and 6.0 g/kg)groups.The mice were then treated with corresponding agents for 6 successive weeks,during which the body weight and liver weight were measured.At the end of the experiment,liver function indicators including aspar-tate aminotransferase(AST)and alanine aminotransferase(ALT),serum triglyceride(TG)level,and blood glucose level were measured.Hematoxylin-eosin staining and Oil red O staining were adopted to assess the pathological changes in the liver tissue.Real-time quantitative PCR was employed to determine the mRNA levels of genes involved in sugar and lipid metabolism and inflammatory mediators in the liver tis-sue.Western blotting was employed to determine the expression levels of proteins in the insulin and inflammation signaling pathways.Results:A total of 224 targets were predicted to be involved in the treatment of NAFLD with Yinchen Gongying Decoction,among which the core targets included protein kinase B(AKT),foxhead box O(FoxO),Toll-like receptor 4(TLR4),and nuclear factor-kappa B(NF-κB).The enrichment analyses suggested that these targets were involved in insulin resistance,FoxO,lipid metabolism,inflammation,and AKT signa-ling pathways.The animal experiment showed that Yinchen Gongying Decoction reduced the body weight and hepatic lipid deposition,im-proved the liver function,lowered the serum TG level,and ameliorated abnormal glucose metabolism in the mouse model of NAFLD.Further-more,the decoction upregulated the mRNA level of Glut4 and downregulated the mRNA levels of G6Pase,Pepck,Acc,Scd-1,Fasn,Il1β,Il6,Il8,and Il11 in the liver.In addition,Yinchen Gongying Decoction upregulated the protein levels of IRS1,IRS2,p-AKT/AKT,and Glut4,while downregulating the protein levels of FoxO1,TLR4,p-NF-κB/NF-κB,IL-1β,IL-6,and IL-17A in the liver.Conclusion:Yinchen Gongy-ing Decoction ameliorates NAFLD by enhancing the insulin(IRS1/IRS2/AKT/FoxO1)signaling pathway and inhibiting the inflammation(TLR4/NF-κB)signaling pathway.关键词
茵陈公英汤/网络药理学/非酒精性脂肪性肝病/糖代谢/脂代谢/胰岛素抵抗/炎症Key words
Yinchen Gongying Decoction(茵陈公英汤)/Network pharmacology/Non-alcoholic fatty liver disease/Glucose metabolism/Lip-id metabolism/Insulin resistance/Inflammation引用本文复制引用
宋汶轩,郝思钰,韩小蕾,胡宝丰,齐亚娟,李爽,安梦娇,李佳琪,郭纪元,蒋声赫,李沙,储金秀,安春娜..茵陈公英汤通过IRS/AKT/FoxO1和TLR4/NF-κB信号通路改善非酒精性脂肪肝病[J].中药药理与临床,2025,41(2):8-15,8.基金项目
河北省中医药联合基金重点项目(编号:H2022209087) (编号:H2022209087)
河北省自然科学基金项目(编号:H2021209013) (编号:H2021209013)
国家自然科学基金项目(编号:81471022) (编号:81471022)
河北省高等学校科学技术研究项目(编号:ZD2022141). (编号:ZD2022141)