Alternative approach for mitigation of doxorubicin-induced cardiotoxicity using herbal agents

Doxorubicin (DOX) is an effective and frequently used chemotherapeutic agent for various malignancies. However, its clinical use is hampered due to the development of cardiotoxicity. Investigations have proved that DOX-induced cardiotoxicity occurs through mechanisms other than those mediating its antitumor effect. This theory sheds light on the development of strategies for cardioprotection without altering therapeutic effectiveness of DOX. Bioactive plant constituents of dietary supplements, traditional herbs and foods with potential health benefits can play an important role in therapeutics. This manuscript is an exhaustive review and prospect of herbal and botanical agents against DOX-induced cardiotoxicity with their proposed mechanisms. The activity of herbs evaluated against DOX-induced cardiotoxicity has shown number of mechanisms including apoptosis, antioxidant potential, effect on mitochondria and calcium ion regulation etc. The manuscript reveals that most of the herbal drugs studied are effective through antioxidant mechanism and only few through other major pathways such as apoptosis and iron mediated pathways in DOX-induced cardiotoxicity. Only limited reports are available for the prevention of DOX-induced drug resistance using botanicals. Manuscript reports a number of constituents with evident potential in prevention of DOX cardiotoxicity e.g. proanthocyanidins, epigallocatechin-3-gallate, S-allylcysteine, reseveratrol, rutoside etc. In the present communication, several herbal drugs have also been discussed, which can act through mechanisms other than antioxidant and may be evaluated as a combination therapy for prevention of DOX-induced cardiotoxicity in future.