Identification of Potential Bioactive Ingredients and Mechanisms of the Guanxin Suhe Pill on Angina Pectoris by Integrating Network Pharmacology and Molecular Docking.
Mingmin WangShuangjie YangMingyan ShaoQian ZhangXiaoping WangLinghui LuSheng GaoYong WangWei WangPublished in: Evidence-based complementary and alternative medicine : eCAM (2021)
The Guanxin Suhe pill (GSP), a traditional Chinese medicine, has been widely used to treat angina pectoris (AP) in Chinese clinical practice. However, research on the bioactive ingredients and underlying mechanisms of GSP in AP remains scarce. In this study, a system pharmacology approach integrating gastrointestinal absorption (GA) evaluation, drug-likeness (DL) evaluation, target exploration, protein-protein-interaction analysis, Gene Ontology (GO) enrichment analysis, network construction, and molecular docking was adopted to explore its potential mechanisms. A total of 481 ingredients from five herbs were collected, and 242 were qualified based on GA and DL evaluation. Target exploration identified 107 shared targets between GSP and AP. Protein-protein interaction identified VEGFA (vascular endothelial growth factor A), TNF (tumor necrosis factor), CCL2 (C-C motif chemokine ligand 2), FN1 (fibronectin 1), MMP9 (matrix metallopeptidase 9), PTGS2 (prostaglandin-endoperoxide synthase 2), IL10 (interleukin 10), CXCL8 (C-X-C motif chemokine ligand 8), IL6 (interleukin 6), and INS (insulin) as hub targets for GSP, which were involved in the inflammatory process, ECM proteolysis, glucose metabolism, and lipid metabolism. GO enrichment identified top pathways in the biological processes, molecular functions, and cell components, explaining GSP's potential AP treatment mechanism. Positive regulation of the nitric oxide biosynthetic process and the response to hypoxia ranked highest of the biological processes; core targets that GSP can regulate in these two pathways were PTGS2 and NOS2, respectively. Molecular docking verified the interactions between the core genes in the pathway and the active ingredients. The study lays a foundation for further experimental research and clinical application.
Keyphrases
- molecular docking
- protein protein
- molecular dynamics simulations
- vascular endothelial growth factor
- small molecule
- transcription factor
- nitric oxide
- pet ct
- rheumatoid arthritis
- coronary artery disease
- type diabetes
- coronary artery
- clinical practice
- endothelial cells
- oxidative stress
- hydrogen peroxide
- climate change
- nitric oxide synthase
- atrial fibrillation
- bone marrow
- network analysis
- drug induced
- adipose tissue
- extracellular matrix
- liver injury
- fatty acid
- copy number
- risk assessment
- acute coronary syndrome
- smoking cessation