Saponins and their derivatives: Potential candidates to alleviate anthracycline-induced cardiotoxicity and multidrug resistance

Anthracyclines (ANTs) continue to play an irreplaceable role in oncology treatment. However, the clinical application of ANTs has been limited. In the first place, ANTs can cause dose-dependent cardiotoxicity such as arrhythmia, cardiomyopathy, and congestive heart failure. In the second place, the development of multidrug resistance (MDR) leads to their chemotherapeutic failure. Oncology cardiologists are urgently searching for agents that can both protect the heart and reverse MDR without compromising the antitumor effects of ANTs. Based on in vivo and in vitro data, we found that natural compounds, including saponins, may be active agents for other both natural and chemical compounds in the inhibition of anthracycline-induced cardiotoxicity (AIC) and the reversal of MDR. In this review, we summarize the work of previous researchers, describe the mechanisms of AIC and MDR, and focus on revealing the pharmacological effects and potential molecular targets of saponins and their derivatives in the inhibition of AIC and the reversal of MDR, aiming to encourage future research and clinical trials.