Effects and Mechanisms of Ban-Xia Xie-Xin Decoction on Type 2 Diabetes Mellitus: Network Pharmacology Analysis and Experimental Evidence

Abstract

Background: Studies have indicated that Ban-Xia Xie-Xin Decoction (BXXXD) has therapeutic effects on type 2 diabetes mellitus (T2DM). However, due to the complexity of components and diversity of targets, the mechanisms are still not fully elucidated. Objective: In this research, we systematically analysed the targets of BXXXD through the method of network pharmacology and further validated them through experiments. Methods: The active components and therapeutic targets were identified, and these targets were analysed by the methods of gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) analysis. Then, based on these network pharmacology analyses, we validated the main targets through animal experiments. Results: A total of 169 active components and 159 targets were identified. KEGG analysis showed that the mitogen-activated protein kinase (MAPK) signalling pathway, tumour necrosis factor (TNF) signalling pathway, the phosphatidylinositol 3' -kinase (PI3K), Akt signalling pathway, and other pathways were related to the treatment of T2DM by BXXXD. PPI network analysis showed that the key genes included signal transducers and activators of transcription 3 (STAT3), JUN, TNF, Recombinant V-Rel Reticuloendotheliosis Viral Oncogene Homolog A (RELA), Akt/PKB- 1 (Protein kinase B), TP53, mitogen-activated protein kinase-1 (MAPK-1), mitogen-activated protein kinase-3 (MAPK-3), interleukin- 6 (IL6), and mitogen-activated protein kinase-14 (MAPK- 14), respectively. Animal experiments showed that BXXXD could reduce blood glucose and improve insulin resistance, which may be related to the mechanisms of inhibiting TNF, interleukin-1 (IL-1), IL-6, and interleukin-17 (IL-17) and promoting Akt phosphorylation. Conclusion: Our research revealed the mechanisms of BXXXD in the treatment of diabetes, which laid a solid foundation for further studies on the molecular mechanisms of BXXXD in the treatment of T2DM.