Molecular Mechanism of Jiedu Tongluo Tiaogan Formula to Improve T2DM-IR Through PI3K/AKT Signaling Pathway Explored Based on TCM Integrated Network Pharmacology and in Vitro Experiments
10.11842/wst.20240427005
- VernacularTitle:基于中医药整合网络药理学和体外实验探究解毒通络调肝方通过PI3K/AKT信号通路改善T2DM-IR的分子机制
- Author:
Cui WU
1
;
Qi ZHANG
;
Pei LI
;
Li WANG
;
Tianjiao LIU
;
Yuandong LI
;
Chunli PIAO
Author Information
1. 长春中医药大学中医学院 长春 130117
- Publication Type:Journal Article
- Keywords:
Network pharmacology;
Jiedu Tongluo Tiaogan Formula;
type 2 diabetes mellitus;
insulin resistance;
in vitro;
PI3K/AKT
- From:
World Science and Technology-Modernization of Traditional Chinese Medicine
2025;27(4):1150-1164
- CountryChina
- Language:Chinese
-
Abstract:
Objective Jiedu Tongluo Tiaogan Formula(JTTF)is an effective formula for the clinical treatment of type 2 diabetes mellitus(T2DM).We used integrated pharmacology and in vitro experiments to explore the molecular mechanism of JTTF to improve insulin resistance(IR)in T2DM.Methods The drug targets of JTTF were obtained by identifying the key active ingredients of JTTF through UPLC-Q-TOF-MS.Multiple databases such as GeneCards,OMIM,and DrugBank were used to screen T2DM-IR related targets.Cytoscape software and String 11.0 database were used to construct the PPI network diagram of JTTF for T2DM-IR.GO and KEGG analyses were performed according to the Metascape platform to find the biological pathways related to the target proteins.AutoDock Tools software was used to simulate molecular docking.In vitro experiments were performed using palmitic acid(PA)-induced HepG2-IR cell model to detect the effect of JTTF on HepG2-IR.Results 28 effective active components of JTTF were screened.There were 857 gene targets of T2DM-IR,and 168 targets of drug-disease intersection.387 GO entries and 145 KEGG pathways were enriched.The molecular docking results showed that the main components of JTTF had good binding activities with PI3K and AKT-related proteins.The in vitro results showed that JTTF significantly alleviated PA-induced HepG2 cell injury,increased HepG2 glucose consumption,increased PI3K and AKT mRNA and protein expression,regulated the expression of GLUT2,GLUT4 and GSK3β,and improved cellular IR.Conclusion JTTF increases insulin sensitivity of HepG2-IR cells,promotes glucose uptake and intracellular glucose metabolism process,and its mechanism of action may be related to the up-regulation of PI3K/AKT signalling pathway.
