Astragaloside A Attenuates Oxaliplatin-Induced Cardiotoxicity, Oxidative Stress, Apoptosis, and Calcium Overload in H9c2 Cardiomyoblasts
Abstract
Background: Oxaliplatin is a widely used platinum-based chemotherapeutic agent, and its cardiotoxicity remains an important safety concern during cancer treatment. Astragalus-derived saponins have been reported to exert cardioprotective effects; however, the specific active constituent responsible for protecting against oxaliplatin-induced myocardial injury has not been identified.
Methods: Several Astragalus saponins and related constituents were screened in oxaliplatin-treated H9c2 cardiomyoblasts. The lead compound was then evaluated in concentration-response experiments for protective efficacy and cytocompatibility. Oxidative stress, apoptosis, caspase-3 activation, calcium overload, and NCX-1 expression were assessed to explore the underlying mechanisms.
Results: Astragaloside A emerged as the most effective compound for restoring cell viability; at 1 and 2 μM, it significantly attenuated oxaliplatin-induced H9c2 cell injury without detectable cytotoxicity. Mechanistically, astragaloside A reduced intracellular reactive oxygen species accumulation, inhibited early and late apoptosis, decreased cleaved caspase-3 expression, alleviated oxaliplatin-induced calcium overload, and increased NCX-1 expression — consistent with enhanced calcium extrusion.
Conclusion: These findings demonstrate that astragaloside A protects H9c2 cardiomyoblasts against oxaliplatin-induced cardiotoxicity by suppressing oxidative stress, apoptosis, and calcium dysregulation. The results support further investigation of astragaloside A as a cardioprotective candidate in oxaliplatin-induced cardiotoxicity.
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References
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