Spice-Based Phytotherapeutics for Drug-Induced Cardiotoxicity: Molecular Targets and Experimental Evidence

Drug-induced cardiotoxicity represents a critical bottleneck while using a few medications, yet current cardioprotective strategies remain limited by suboptimal clinical efficacy and lack of mechanism-based precision. In traditional medicine systems, spices have long been utilized to treat various ailments due to their abundance in phytochemicals, particularly polyphenols, essential oils, and flavonoids. While significant preclinical evidence exists for the cardioprotective efficacy of specific spice-derived phytotherapeutics, the field lacks a fundamental understanding of how these agents converge onto common biological pathways. The work critically examines the comparative efficacy and molecular mechanisms of various spices to determine their potential as standardised, adjuvant cardioprotective treatments in drug-induced cardiotoxicity. We conducted comprehensive searches in English-restricted databases, including PubMed, Scopus, and Web of Science. It delves into the roles and mechanisms of spice-derived botanicals like cardamom, coriander, curry leaf, fenugreek, garlic, ginger, long pepper, saffron, and turmeric. This review provides an overview of preclinical and clinical studies focusing on the potential of spice-derived phytotherapeutics in managing drug-induced cardiotoxicity, notably those induced by doxorubicin, isoproterenol, Trastuzumab and paracetamol. Our synthesis finds that while individual spices show promise, their cardioprotective potential would be enhanced through combinational or advanced formulation techniques through various mechanisms, including the reduction of lipid peroxidation, restoration of antioxidant status, modulation of calcium ion concentration, and inhibition of inflammatory and apoptotic pathways, which challenge conventional therapy. The findings of this review underscore the potential for developing natural strategies to protect the heart from specific drug-induced cardiotoxicity.