Medicinal Plants and Phytochemicals in Cardioprotection—Mechanistic Pathways and Translational Roadmap

Despite major advances in guideline-directed cardiovascular therapy, residual cardiovascular risk persists, partly driven by oxidative stress, chronic inflammation, endothelial dysfunction, and mitochondrial injury not fully addressed by current drugs. Translation of plant-based cardioprotectants is constrained by preparation-dependent variability in extract chemistry (plant part/cultivar/processing and extraction method), low and variable systemic exposure for key actives (notably curcuminoids and many polyphenols), and clinically relevant safety/interaction considerations (e.g., hepatotoxicity reports with concentrated green tea extracts and antiplatelet-related bleeding-risk considerations for some botanicals). We therefore provide a mechanism- and translation-oriented synthesis of evidence for cardioprotective botanicals, chosen for long-standing traditional use and scientific validation with reproducible experimental data and, where available, human studies, including Crataegus monogyna, Allium sativum, Olea europaea, Ginkgo biloba, Leonurus cardiaca, and Melissa officinalis. Across studies, polyphenols (especially flavonoids and phenolic acids) and organosulfur compounds are most consistently associated with cardioprotection, while terpene-derived constituents and secoiridoids contribute mechanistically in plant-specific settings (e.g., Ginkgo and Olea). Predominantly in experimental models, these agents engage redox-adaptive (Nrf2), mitochondrial (mPTP), endothelial, and inflammatory (NF-κB) pathways, with reported reductions in ischemia–reperfusion injury, oxidative damage, and apoptosis. Clinical evidence remains heterogeneous and is largely confined to short-term studies and surrogate outcomes (blood pressure, lipids, oxidative biomarkers, endothelial function), with scarce data on hard cardiovascular endpoints or event reduction. Priorities include standardized, chemotype-controlled formulations with PK/PD-guided dosing and adequately powered randomized trials that assess safety and herb–drug interactions.