Analysis of Modular Network Mechanism of Danhong Injection in Treatment of Coronary Angina Pectoris / 中国实验方剂学杂志

ABSTRACT

Objective:To explore the pharmacological mechanism of Danhong injection (DHI) in the treatment of coronary heart disease with angina pectoris from the level of functional modules by modular pharmacological analysis framework. Method:The targets of drug components in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the angina-related genes in DisGeNET, OMIM and CTD databases were combined to construct the target network of DHI for the treatment of coronary angina pectoris by STRING version 11.0. Functional modules were identified by the molecular complex detection (MCODE), Markov cluster (MCL) and GLay algorithms, and the results were optimized by the minimum network structure entropy algorithm. The Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis was performed on the modules by DAVID version 6.8 bioinformatics analysis platform. Result:By integrating 262 genes related to DHI and 192 genes related to angina pectoris, the target network of DHI for angina pectoris was constructed, including 414 nodes and 6 621 edges. After optimization of the minimum network structure entropy, 12 functional modules (number of nodes>3) were identified by MCODE algorithm, of which the largest module (module 1) has 47 nodes and 962 edges, MCODE score=41.826. KEGG pathway enrichment analysis was conducted on the gene network of DHI for angina pectoris and the modules divided by MCODE, and 37 and 58 KEGG signaling pathways were obtained respectively, with the coverage rate of 86.5%. The pathways enriched by the modules could be roughly divided into 11 categories, among which human diseases (45%), signal transduction (17%), and amino acid metabolism (14%) were involved in a large proportion. Module 1 was enriched into 39 pathways, which was signal transduction-related module. Module 3 was amino acid metabolism-related module. Conclusion:The therapeutic effect of DHI on coronary heart disease with angina pectoris is achieved through multiple modules, multiple pathways and multiple functions, mainly by regulating modules related to signal transduction, amino acid metabolism, neuroactive ligand-receptor interaction, Ca2+ and p53 signaling.