Phytomedicine in Cardiovascular Disease: Molecular Mechanisms, Clinical Evidence, and Translational Challenges

Abstract

Cardiovascular diseases remain a major cause of morbidity and mortality worldwide and arise from interacting disturbances in vascular function, inflammation, redox regulation, lipid and energy metabolism, mitochondrial homeostasis, cardiac remodelling, and thrombosis. Plant-derived compounds have attracted considerable interest because many influence more than one of these processes. This review examines the cardiovascular relevance of major phytochemicals and botanical preparations, with emphasis on their molecular mechanisms, experimental evidence, clinical findings, and barriers to therapeutic translation. Particular attention is given to signalling pathways involving Nrf2, eNOS, AMPK, sirtuins, PI3K/Akt, NF-κB, NLRP3, and TGF-β/Smad, and to their relevance in endothelial dysfunction, hypertension, atherosclerosis and dyslipidaemia, myocardial ischaemia/reperfusion injury, heart failure, cardiac remodelling, and thrombosis. Although experimental studies provide substantial evidence of biological activity, the strength of clinical evidence is uneven. Many human studies rely on biomarkers or physiological endpoints, whereas evidence for patient-important cardiovascular outcomes remains limited. Translation is further complicated by poor or variable bioavailability, metabolism to active or inactive derivatives, differences in botanical composition and standardisation, uncertain tissue exposure, and potential herb-drug interactions. A clinically meaningful assessment, therefore, requires evidence that a reproducible intervention achieves sufficient systemic or tissue exposure, engages the proposed molecular target, produces a measurable pharmacodynamic response, and ultimately improves relevant cardiovascular outcomes. Greater attention to pharmacokinetics, preparation-specific standardisation, adequately powered clinical trials, clinically meaningful endpoints, and long-term safety will be necessary to determine which phytomedicines can progress from promising experimental agents to evidence-based cardiovascular interventions.