Abstract: Objective To investigate the protective effect of Schisandrin B, an important active component of Schisandra chinensis, against cyclophosphamide- and epirubicin-induced cardiotoxicity and to explore its dose-effect relationship. Methods Mouse models of cardiotoxicity were established using cyclophosphamide and epirubicin, respectively. For each model, male C57BL/6N mice aged 6-8 weeks were randomly divided into five groups (n=10 per group): the control group, model group, model + low-dose Schisandrin B group (10 mg·kg^-1·d^-1), model + medium-dose Schisandrin B group (30 mg·kg^-1·d^-1), and model + high-dose Schisandrin B group (100 mg·kg^-1·d^-1). Schisandrin B was administered by oral gavage once daily for 4 consecutive weeks while cyclophosphamide and epirubicin were injected intraperitoneally once weekly for 4 consecutive weeks, respectively. Left ventricular systolic function was evaluated by echocardiography while left ventricular ejection fraction and fractional shortening were observed. Serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and aspartate aminotransferase (AST) were measured. Cardiac pathological sections were examined for morphological changes in cardiomyocytes, including vacuolization and other early apoptotic features. Results In both the cyclophosphamide model group and the epirubicin model group, left ventricular ejection fraction and fractional shortening were significantly decreased while serum NT-proBNP and AST levels were markedly elevated. No obvious changes in overall heart size were observed, but significant cardiomyocyte vacuolization was present in both models. Following schisandrin B intervention, all the above parameters—cardiac systolic function, serum cardiac injury biomarkers, and the degree of cardiomyocyte vacuolization—were significantly improved. Moreover, improvements increased with the dose of Schisandrin B, which suggested a dose-effect relationship. Conclusion Schisandrin B can dose-dependently attenuate cyclopho-sphamide- or epirubicin-induced cardiotoxicity, potentially through such mechanisms as anti-oxidative stress and inhibition of apoptosis, suggesting its potential to be used as an adjunctive cardioprotective agent during cancer chemotherapy.

Key words: Schisandrin B, Cyclophosphamide, Epirubicin, Cardiotoxicity, Dose-Effect Relationship, Oxidative Stress, Mice