Simiao Wan alleviates obesity-associated insulin resistance via PKCε/IRS-1/PI3K/Akt signaling pathway based on network pharmacology analysis and experimental validation  

作　　者：Jing Jin Yin-Yue Xu Wen-Ping Liu Ke-Hua Hu Ning Xue Zu-Guo Zheng 

机构地区：[1]State Key Laboratory of Natural Medicines,China Pharmaceutical University,Nanjing 210009,China [2]Department of Acupuncture,Jurong Hospital Affiliated to Jiangsu University,Zhenjiang 212499,China

出　　处：《Traditional Medicine Research》2023年第10期56-68,共13页TMR传统医学研究

基　　金：supported by the National Natural Science Foundation of China(81903871);Natural Science Foundation of Jiangsu Province(BK20190565);Fundamental Research Funds for the Central Universities(2632021ZD16);Zhenjiang City 2022 Science and Technology Innovation Fund(SH2022084).

摘　　要：Background:The purpose of the study was to investigatethe active ingredients and potential biochemicalmechanisms of Simiao Wan(SMW)in obesity-associated insulin resistance.Methods:An integrated network pharmacology method to screen the active compoundsand candidate targets,construct the protein-protein-interaction network,and ingredients-targets-pathways network was constructed for topological analysis to identify core targets and main ingredients.To find the possible signaling pathways,enrichment analysis was performed.Further,a model of insulin resistance in HL-7702 cells was established to verify the impact of SMW and the regulatory processes.Results:An overall of 63 active components and 151 candidate targets were obtained,in which flavonoids were the main ingredients.Enrichment analysis indicated that the PI3K-Akt signaling pathway was the potential pathway regulated by SMW in obesity-associated insulin resistance treatment.The result showed that SMW could significantly ameliorate insulin sensitivity,increase glucose synthesis and glucose utilization and reduce intracellular lipids accumulation in hepatocytes.Also,SMW inhibited diacylglycerols accumulation-induced PKCεactivity and decreased its translocation to the membrane.Conclusion:SMW ameliorated obesity-associated insulin resistance through PKCε/IRS-1/PI3K/Akt signaling axis in hepatocytes,providing a new strategy for metabolic disease treatment.

关 键 词：Simiao Wan insulin resistance PKCε/IRS-1/PI3K/Akt signaling pathway network pharmacology DAG 

分 类 号：R285[医药卫生—中药学]