Abstract
BACKGROUND: Shexiang Baoxin Pill (SBP) is a classical Chinese medicine that improves endothelial function and antioxidant and inflammatory responses. It may also alleviate doxorubicin (DOX)-induced cardiotoxicity. The aim of this study is to explore the potential influence and molecular mechanisms of SBP in DOX-induced cardiotoxicity using network pharmacology. METHODS: We established control, SBP, DOX, and DOX + SBP groups to evaluate cell function using a Cell Counting Kit-8 assay, reactive oxygen species (ROS) measurement, cell cycle analysis, and apoptosis assessment. Network pharmacology was employed to predict potential targets and pathways of SBP in DOX-induced cardiotoxicity; the predictions were validated using protein blotting assays. RESULTS: SBP (2.5 mg/L) significantly mitigated DOX-induced cardiotoxicity. DOX elevated ROS levels, induced phosphorylation of the AKT pathway, and altered the expression of apoptosis-related proteins Bcl-2 and Bax. SBP attenuated the impact of DOX on cardiomyocytes. Network pharmacology identified 10 candidate targets. CONCLUSION: SBP ameliorates DOX-induced cardiomyocyte apoptosis by activating the ROS-mediated AKT/Bcl-2 signaling pathway.