Mechanism of <italic>Coptis chinensis</italic> in Treatment of Type 2 Diabetes Mellitus Based on Network Pharmacology and Molecular Docking

Abstract

<sec><title>Objective</title> To explore the mechanism of <italic>Coptis chinensis</italic> in the treatment of type 2 diabetes mellitus based on network pharmacology and molecular docking. </sec><sec><title>Methods</title> The active chemical ingredients of <italic>Coptis chinensis</italic> were screened through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), oral bioavailability (OB) ≥30% and drug-likeness (DL) ≥0.18 were set. The corresponding target of active ingredients and related targets of type 2 diabetes mellitus were retrieved through UniProt database and CTD database; Cytoscape 3.6.1 software was used to make the visual network diagram of <italic>Coptis chinensis</italic>-active ingredients-targets, and STRING database was used to construct the PPI network diagram of intersection targets, and the core targets were analyzed by GO function enrichment and KEGG pathway enrichment. In addition, molecular docking was conducted between the core targets and the active ingredients of <italic>Coptis chinensis</italic> to verify the binding ability between the active ingredients and the core targets. </sec><sec><title>Results</title> ① A total of 14 active ingredients of <italic>Coptis chinensis</italic>, 189 targets for the treatment of type 2 diabetes mellitus were screened out, among which 136 potential targets were identified, including 20 core targets (degree≥12), 137 signaling pathways with significant significance. ② Gene Ontology (GO) functional enrichment analysis showed that, the biological processes (BP) involved in the predicted target of <italic>Coptis chinensis</italic> in the treatment of type 2 diabetes mellitus involved gland development, epithelial cell proliferation, regulation of DNA-binding transcription factor activity, oxidative stress and apoptosis response to lipopolysaccharide, etc. In terms of molecular function (MF), it involved DNA transcription factor binding, enzyme binding, receptor binding and other reactions. In terms of cell components (CC), it involved the composition of enzyme regulated complex, cystic cavity, membrane microregion and membrane region. ③ Components-target-pathway network analysis showed that, the main potential active ingredients of <italic>Coptis chinensis</italic> in the treatment of type 2 diabetes mellitus were quercetin, berberine, etc. It can act on mitogen-activated proteinase 1 (MAPK1), serine/threonine protein kinase (AKT1), tumor protein p53 (TP53), transcription factor AP-1 (JUN), tumor necrosis factor (TNF), interleukin-6 (IL-6), which can regulate MAPK, AGEs-RAGE, PI3K-Akt, Toll-like receptors, HIF-1, TNF signaling pathways, etc. ④ The molecular docking results showed that, the molecular docking affinity between the active ingredients of <italic>Coptis chinensis</italic> and the above core targets was less than -7.0 kcal/mol (1 kca/mol=4.186 kJ/mol), and the binding activity was better. </sec><sec><title>Conclusion</title> <italic>Coptis chinensis</italic> may play an important role in the treatment of type 2 diabetes mellitus and its complications by regulating glucose and lipid metabolism, inflammatory response, cell proliferation and apoptosis and promoting oxidative stress, etc. </sec>