Cardioprotective effect of Renshen-Danshen prescription against doxorubicin-induced cardiotoxicity in vitro and in vivo

Aims of the study: To investigate the effects of RD (Renshen-Danshen) against doxorubicin (DOX)cardiotoxicity and its possible molecular mechanismsMaterials and methods: Ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was used to analyze the whole components of RD, and combined with network pharmacology and cellular transcriptomics to analyze the therapeutically relevant pathways and core targets of RD, and to establish in vitro and in vivo DOX models to verify the therapeutic efficacy and mechanism of action of RD.Results: The therapeutic effect of RD on DOX-induced cardiotoxicity was found to be associated with apoptosis due to oxidative stress by phytochemical analysis combined with bioinformatics analysis, and the core targets consisted of CASP3, BCL2, SESN2, SIRT1, and AMPK. RD improved the cardiac function and level of myocardial fibrosis of doxorubicin-induced cardiac injury rats in vivo, and reduced the myocardial injury markers, oxidative stress markers, and cardiomyocyte apoptosis. In addition, RD decreased the expression levels of BAX and Cleaved-Caspse-3 in oxidative stress and apoptosis signaling pathways in vitro and in vivo, and restored SIRT1, NRF2, p-AMPK, SESN2, and Bcl-2 protein levels.Conclusions: In conclusion, RD attenuated DOX-induced abnormal cardiac function, myocardial fibrosis, oxidative stress and apoptosis. This study suggests that RD has a therapeutic effect on DOX-induced cardiac injury and is a good choice for its complementary therapy, and the potential molecular mechanism maybe to regulate the SIRT1/SESN2 signaling pathway, which needs to be further investigated.