Distinguish the Characteristic Mechanism of 3 Drug Pairs of Corydalis Rhizome in Ameliorating Angina Pectoris: Network Pharmacology and Meta-Analysis

Abstract

Objective: Angina pectoris (AP), affecting over 523 million people, can be alleviated by corydalis rhizome (CR), usually combined with chuanxiong rhizome (CXR), angelica dahuricae radix (ADR), or astragali radix (AR) to enhance the effect. This study aims to distinguish the different mechanisms among 3 drug pairs to treat AP. Methods: The drug pair-disease intersection targets, compound targets, protein–protein interaction (PPI), and herb-compound-target-pathway network were obtained by Cytoscape, STRING, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses ( http://www.kegg.jp/ or http://www.genome.jp/kegg/ ). Importantly, with principal component analysis (PCA), the key point of KEGG and GO were explored and supported, while by meta-analysis, the different mechanisms of the drug pairs on AP were discovered. Results: JUN, SRC, PIK3CA, and MAPK1 as PPI core network of CR-AP, (CR-CXR)-AP, (CR-ADR)-AP, and (CR-AR)-AP. (highest confidence > 0.9). 10, 45, 35, and 21 key compounds, and 68, 123, 117, and 97 core targets were obtained from CR-AP, (CR-CXR)-AP, (CR-ADR)-AP, and (CR-AR)-AP based on more than 2-fold median value for degree and betweenness centrality, more than the median of closeness centrality. The core pathways of (CR-CXR)-AP and (CR-AR)-AP cover “fluid shear stress and atherosclerosis” and the “pathways in cancer”, while (CR-ADR)-AP was found as the “pathways in cancer” by PCA and KEGG ( P < .01). The core biological processes of (BP) (CR-CXR)-AP, (CR-ADR)-AP, and (CR-AR)-AP were all enriched in the “circulatory system process” by PCA and GO ( P < .01). Moreover, meta-analysis indicated the significant differences ( P < .05) of the 3 drug pairs. Conclusion: CR-CXR, CR-ADR, or CR-AR outperformed CR-AP in AP mitigation. Furthermore, meta-analysis revealed, CR-CXR was superior to alleviating AP by affecting “circulatory system process” and “fluid shear stress and atherosclerosis”, particularly the targets PTGS1, PTGS2, ADRB2, ADRA2C, and NOS, when compared with the drug pair of CR-ADR and the CR-AR.