Polyphenols and Cardiovascular Diseases: Molecular Insights and Nutraceutical Advances

Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide. Despite their often-asymptomatic progression and complex therapeutic management, a substantial proportion of CVDs is preventable through early intervention and lifestyle modification. However, effective pharmacological strategies to fully reduce disease burden and associated risk factors remain limited. Polyphenols are a structurally diverse class of bioactive compounds widely distributed in plant-based foods, characterized by multiple phenolic and hydroxyl groups that confer potent redox-modulating properties. Increasing evidence indicates that dietary polyphenols exert cardioprotective effects through antioxidant, anti-inflammatory, and endothelial-modulating mechanisms. Experimental studies (in vitro and in vivo) have demonstrated that polyphenols regulate key molecular pathways involved in oxidative stress, inflammation, and vascular function, including PI3K/Akt/eNOS, AMPK/SIRT1, and Nrf2 signaling. In parallel, epidemiological and clinical evidence support their association with improvements in blood pressure, glycemic control, lipid profiles, and body weight, critical determinants of cardiovascular risk. Importantly, the biological response to polyphenol intake is highly variable and influenced by genetic background, metabolism, gut microbiota composition, and bioavailability constraints. This review provides an updated and integrative analysis of the molecular mechanisms underlying the cardioprotective effects of polyphenols, emphasizing their role in endothelial function and nitric oxide bioavailability. Additionally, it highlights recent advances in polyphenol-based nutraceuticals, discusses translational limitations, and outlines future perspectives for their application in cardiovascular disease prevention and management.