Based on network pharmacology and experiments to explore the potential mechanism of Radix Puerariae- Radix Trichosanthis and Radix Astragali-Radix Rehmanniae in the treatment of T2DM

Abstract

Abstract Background: There are many traditional Chinese medicine prescriptions for the treatment of type 2 diabetes (T2DM), but most of them are not simple enough, which increase the economic burden of patients. Radix Astragali, Radix Puerariae, Radix Trichosanthis and Radix Rehmanniaeare the four traditional Chinese medicines commonly used in the treatment of T2DM. However, the molecular mechanism of these four drugs in the treatment of diabetes is still unclear. Therefore, this study is the first to explore the potential mechanism of Astragali-Rehmanniaeare and Puerariae-Trichosanthis in the treatment of T2DM through network pharmacology and animal experiments.Methods: First we obtained the active chemical components and targets of these four drugs. Then the main targets of diabetes were obtained and protein-protein interaction was built by String. Metascape platform was used to analyze the "drug-component-target" and the biological processes and pathways they involved. Finally, "Drug-Diabetes-Pathway" network was conducted. Subsequently, animal experiments were conducted to verify the network analysis results. Blood glucose of two hours postprandial was measured every week. The insulin expression level was measured to calculate HOMA-IR and HOMA-β, and the protein expressions of PI3K and Akt were measured as well.Results: The core active components were quercetin, daidzein, kaempferol, puerarin, formononetin; the core targets includedAKT1, PIK3CA, TNF, etc. The biological pathway mainly acted on PI3K-Akt signaling pathway and insulin resistance pathway. The experiment results showed that the drug groups could significantly reduce the blood glucose of T2DM rats. HOMA-IR of Astragali-Rehmanniaeare was significantly decreased, and HOMA-β of Puerariae-Trichosanthis was significantly increased. PI3K protein in Astragali-Rehmanniaeare and Puerariae-Trichosanthis was significantly higher than that in control group. Akt protein in Astragali-Rehmanniaeare was significantly higher than that in control group, but significantly lower than that in model group.Conclusions: Astragali-Rehmanniaeare and Puerariae-Trichosanthis improved blood glucose mainly by changing the contents of PI3K and Akt in the body to affect the PI3K-Akt signaling pathway, so as to achieve the purpose of treating T2DM.