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

Autor: Jing Jin, Yin-Yue Xu, Wen-Ping Liu, Ke-Hua Hu, Ning Xue, Zu-Guo Zheng
Předmět:
Zdroj: Traditional Medicine Research; Oct2023, Vol. 8 Issue 10, p1-13, 13p
Abstrakt: 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 PKCε activity 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index