Cardioprotective Potential of Medicinal Plants in Attenuating Doxorubicin-Induced Cardiotoxicity

Doxorubicin (DOX) is a potent and widely used anthracycline antibiotic as anti-cancer drug; however, it also causes dose-dependent organ toxicity, mainly cardiotoxicity. The occurrence of fatal cardiotoxicity characterized by an irreversible cardiomyopathy often compromised the clinical usage of DOX. The appearance of association between significant burden of cancer and chemotherapy-induced cardiotoxicity brings enthusiasm among researchers for search of targeted strategies that can simultaneously provide long-term cardio-protection from DOX-associated cardiotoxicity without compromising the efficacy of DOX. Numerous preclinical and human studies reveal that oxidative stress, inflammation and subsequent cardiomyocytes apoptosis are the primary pathogenic mechanisms leading to cardiomyopathy. The clinical application of traditional cytotoxic drugs remains to continue a favored mode for the treatment of cancer due to inadequacies of presently available adjuvants in terms of pharma-economics, short-term efficacy and innate adverse effects. Recently, various dietary plants of natural origin gained attention as anticancer, chemopreventive and cardioprotective agent. Apart from synthetic agent, the naturally occurring plants may prove to be better as adjuvants in chemotherapy. The ideal cardioprotective agents should not interfere with cytotoxicity of DOX and will be devoid of cumulative or irreversible toxicity along with capacity to reverse chemoresistance or chemosensitize the tumor cells to DOX. In the past few years, plant derivedphytochemicals as novel small molecules of natural origin found to either prevent or reverse the cardiotoxicity caused by DOX pursuing disease modifying approach. The present review renders an overview of cardioprotective effects of some promising plants against DOXinduced cardiotoxicity in experimental models. The review employing the synoptic tables documents the cardioprotective potential of plant extracts, the experimental models used and the major mechanism of cardioprotection. The review also discusses the challenges, limitations and future prospects in pharmaceutical development of plants extracts and their potential utilization for further drug development characterizing the potential phytoconstituents attributed to the cardioprotective efficacy. These compounds may provide an alternative and valuable source of ideal, cost-effective, safe adjuvant to chemotherapy utilized for drug discovery and development. These could be utilized as effective cardioprotective agents in management of DOX-associated cardiotoxicity.