Affiliations: [a] School of Food and Biological Engineering, Chengdu University, Chengdu, Sichuan, China | [b] Chongqing Three Gorges Medical College, Chongqing, China | [c] School of Early Childhood Development, Chongqing Preschool Education College, China | [d] Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Chongqing, China | [e] Chinese Medicine Health Application Technology Promotion Center in Chongqing Three Gorges Reservoir Area, Chongqing, China
Correspondence:
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Corresponding authors: Binbin Feng, Chongqing Three Gorges Medical College, Chongqing 404120, China. E-mail: fengbin1024@cqtgmc.edu.cn. Jianhai Zhang, Chongqing Three Gorges Medical College, Chongqing 404120, China. E-mail: jianhaizhang@cqtgmc.edu.cn.
Abstract: BACKGROUND: Jingshen Xiaoke decoction (JS) was prepared by studying the classic prescriptions of famous scholars in the past dynasties to prevent and treat diabetes. The related mechanism of JS against hyperlipidemia has yet to be revealed. OBJECTIVE: To investigate the mechanism of action of JS in treating diabetes mellitus by using bioinformatics methods. METHODS: A database was used to search the active ingredients and targets of the JS and targets for type 2 diabetes mellitus (T2DM). The protein interaction between the intersection targets, and the constructed the PPI network diagram was analyzed using the STRING database. Furthermore, the gene annotation tool DAVID was used to enrich the intersecting targets for the Gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway. Finally, Maestro software was used for molecular docking to verify the binding ability of the active ingredients to the core target genes. RESULTS: A total of 45 active ingredients in JS were screened out corresponding to 239 effective targets, of which 64 targets were potential targets for treating T2DM. The analysis of PPI network diagram analysis revealed that the ingredients’ active components are quercetin, β-sitosterol, stigmasterol, luteolin, and 7-Methoxy-2-methyl isoflavone. GO functional enrichment analysis indicated 186 biological processes (BP), 23 molecular functions (MF) and 13 cellular components (CC). KEGG pathway enrichment analysis revealed the enrichment of 59 signal pathways. The molecular docking results demonstrated that the active ingredients and core targets had a good docking affinity with a binding activity less than -7 kcal/mol. Finally, the western blotting illustrated that JS could up-regulate the liver PI3K/AKT-signaling pathway. CONCLUSION: JS can regulate glucolipid metabolism, reduce the inflammatory response, improve insulin resistance and modulate the immune response through PI3K/AKT signaling pathway treating of T2DM and its complications effects.
Keywords: Jingshen Xiaoke decoction, network pharmacology, molecular docking, type two diabetes mellitus, western blot, mechanism of action, biological activity
