Tongmai Yangxin pills anti-oxidative stress alleviates cisplatin-induced cardiotoxicity: Network pharmacology analysis and experimental evidence.

Abstract

Tongmai Yangxin Pills (TMYXP), a traditional Chinese patent medicine, has been widely used to treat coronary heart disease for few decades. However, the potential protective effect of TMYXP on cisplatin-induced cardiotoxicity has not been reported. The target proteins corresponding to compounds from Pharmmapper database, PubMed database and ChEMBL database were collected and construct a 'TMYXP-compound-target' network. DAVID database was used for annotation and enrichment pathways and String 9.1 database was used for analysis the protein-protein interaction. Cisplatin-induced rat cardiotoxicity model was established to verify the protective effects mechanism of TMYXP. The target proteins corresponding to compounds from multiple databases were collected and construct a TCM-compound-target network to enriched pathways with high enrichment score. GO analysis and enrichment clusters point that response of oxidative stress is the main biological process of TMYXP, and Nrf2 signaling pathway and MAPK signaling pathway might be the key functional pathways. In vivo experiments, we proved that TMYXP improves anti-oxidative stress ability and reduce apoptosis through regulating Nrf2/HO-1 pathway and p38-MAPK pathway. The effects of TMYXP on regulate cardiomyocyte free radical balance and reduce apoptosis, making it possible as a drug candidate for platinum chemotherapeutic induced cardiac injury.