Network pharmacology-based exploration of the mechanism of guanxinning tablet for the treatment of stable coronary artery disease

Abstract

Objective: Network pharmacology was utilized to explore the mechanism of Guanxinning (GXN) tablet for the treatment of stable coronary artery disease (SCAD). Materials and Methods: First, active ingredients and therapeutic targets were predicted by databases and gene chip. Then, we constructed the compound-target (C-T) network and target-disease (T-D) network to screen hub compounds and therapeutic targets based on contribution index (CI), degree, closeness, betweenness, and coreness in the networks. Enrichment analysis was performed on hub therapeutic targets, and finally, the verification of hub ingredients and hub therapeutic targets was performed through molecular docking. Results: With “oral bioavailability ≥30%, druglikeness ≥0.18, and half-life ≥4 h” as screening conditions, 58 active ingredients were obtained. Seven hundred and seventeen compound targets and 636 SCAD targets were retrieved using databases and gene chip, and the intersection of both (139 targets) was defined as therapeutic targets. According to CI, degree, betweenness, closeness, and coreness, 2 hub compounds and 13 hub therapeutic targets were chosen from the C-T network and T-D network, respectively. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that GXN treated SCAD from several aspects including inflammatory reaction, oxidative stress, nutritional metabolism, blood pressure regulation, ventricular remodeling, vascular smooth muscle proliferation, angiogenesis, and platelet aggregation. Tissue enrichment analysis revealed that the therapeutic targets were enriched in multiple organs and tissues. The excellent binding force between the hub compounds and hub therapeutic targets was verified by molecular docking. Conclusions: The treatment of SCAD by GXN has the characteristics of multiple ingredients, multiple targets, and multiple approaches. Consequently, it may theoretically treat SCAD from multiple angles and levels.

Keywords

• gene chip
• guanxinning tablet
• molecular docking
• network pharmacology
• stable coronary artery disease