Network Pharmacology and Experimental Verification Reveal an Protective Role of Jiedu Tongluo Tiaogan Formula on INS-1 Cells and HepG2 Cells From High Glucose-mediated Injury via the PI3K/Akt Pathways

Abstract

Background: T2DM is considered to be a chronic low-grade inflammatory disease, because of its high morbidity and mortality, diabetes poses a tremendous potential threat to public health. Our previous studies have shown that a traditional Chinese medicine formula, Jiedu Tongluo Tiaogan Formula (JDTL) exerts favorable hypoglycemic effect, however, its molecular mechanism and the interaction among various components need to be further elucidated. This study aimed to explore the mechanism of JDTL in the treatment of T2DM using an integrated strategy of system pharmacology, bioinformatics analysis, and experimental verification. Materials and Methods: First, the compounds of JDTL were searched from public databases, and the "compound-target " network was constructed to predict the potential active components and targets. Subsequently, bioinformatics analysis was used to identify potential targets and signaling pathways, including PPI, GO pathways and KEGG pathways. Finally, the pharmacological effects and mechanisms of JDTL were verified by molecular docking and cell experiments. Results: Analysis by GO and KEGG pathway enrichment revealed that these targets were associated with lipopolysaccharide, membrane microdomain, cytokine receptor binding, and JDTL could regulate the PI3K/Akt signaling pathway. Furthermore, we have proved that JDTL could improve the mRNA expression and protein expression of IRS1, AKT, and PI3K in the INS-1 cell and HepG2 cells. Conclusion: The present study elucidated the active ingredients, potential targets, and molecular mechanism of JDTL in the treatment of T2DM, and revealed the characteristics of JDTL in multi-component, multi-target and multi-channel. It also provided an important scientific basis for new drug development and mechanism research of T2DM.