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<p>Cardiotoxicity is a major barrier in the safe use of therapeutic and illicit drugs, causing cardiac dysfunction and mortality through oxidative stress, mitochondrial damage, calcium dysregulation, apoptosis, immune activation, and defective autophagy. This review integrates mechanistic insights and emphasizes plant-derived phytochemicals as promising cardioprotective alternatives or adjuncts. A comprehensive literature survey across PubMed, Scopus, Web of Science, and ScienceDirect (till August 2025) profiled cardiotoxic agents and phytotherapeutics, categorizing mechanisms oxidative stress, apoptosis, mitochondrial dysfunction, calcium imbalance, immune injury and systematically mapping them against plant-derived protective interventions. Analysis revealed that cardiotoxic drugs converge on common molecular targets such as topoisomerase IIβ, mitochondrial respiratory complexes, apoptotic regulators (Bax, cytochrome c, caspases), autophagy proteins (Beclin-1, LC3-II), ion channels and inflammatory mediators (IL-6, TNF-α). Phytochemicals including flavonoids (quercetin, kaempferol, rutin, myricetin), alkaloids (berberine), polyphenols (curcumin, resveratrol), and terpenoids demonstrated multi-targeted cardioprotection. These agents enhanced antioxidant enzymes activity (SOD, CAT, GPx), stabilized mitochondrial dynamics, inhibited pro-apoptotic signaling, modulated calcium homeostasis, suppressed NF-κB–driven inflammation, and improved endothelial function. In vitro, in vivo, and in silico studies consistently supported their cardioprotective efficacy. Plant-derived bioactives exhibit significant promise in counteracting drug-induced cardiotoxicity by targeting interconnected oxidative, apoptotic, and inflammatory pathways. Integrating phytotherapeutics into preclinical and translational studies may accelerate development of safer, mechanism-driven interventions. This work provides a comprehensive framework for leveraging natural compounds as cardioprotective agents and underscores their potential in future drug safety strategies.</p>

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Mechanisms of drug-induced cardiotoxicity and translational potential of natural products in cardio protection

  • 期刊论文

  • 发表日期：

    2026年6月18日

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  • Sourav D. Gore,
  • Priyanka Patil,
  • Shrihari Patil,
  • Shashidhar Patil,
  • Sachin Gudasi

摘要

Cardiotoxicity is a major barrier in the safe use of therapeutic and illicit drugs, causing cardiac dysfunction and mortality through oxidative stress, mitochondrial damage, calcium dysregulation, apoptosis, immune activation, and defective autophagy. This review integrates mechanistic insights and emphasizes plant-derived phytochemicals as promising cardioprotective alternatives or adjuncts. A comprehensive literature survey across PubMed, Scopus, Web of Science, and ScienceDirect (till August 2025) profiled cardiotoxic agents and phytotherapeutics, categorizing mechanisms oxidative stress, apoptosis, mitochondrial dysfunction, calcium imbalance, immune injury and systematically mapping them against plant-derived protective interventions. Analysis revealed that cardiotoxic drugs converge on common molecular targets such as topoisomerase IIβ, mitochondrial respiratory complexes, apoptotic regulators (Bax, cytochrome c, caspases), autophagy proteins (Beclin-1, LC3-II), ion channels and inflammatory mediators (IL-6, TNF-α). Phytochemicals including flavonoids (quercetin, kaempferol, rutin, myricetin), alkaloids (berberine), polyphenols (curcumin, resveratrol), and terpenoids demonstrated multi-targeted cardioprotection. These agents enhanced antioxidant enzymes activity (SOD, CAT, GPx), stabilized mitochondrial dynamics, inhibited pro-apoptotic signaling, modulated calcium homeostasis, suppressed NF-κB–driven inflammation, and improved endothelial function. In vitro, in vivo, and in silico studies consistently supported their cardioprotective efficacy. Plant-derived bioactives exhibit significant promise in counteracting drug-induced cardiotoxicity by targeting interconnected oxidative, apoptotic, and inflammatory pathways. Integrating phytotherapeutics into preclinical and translational studies may accelerate development of safer, mechanism-driven interventions. This work provides a comprehensive framework for leveraging natural compounds as cardioprotective agents and underscores their potential in future drug safety strategies.