Dietary polyphenols in atherosclerosis: a review of molecular mechanisms, endothelial dysfunction, oxidative stress, and vascular inflammation

Atherosclerosis is a chronic inflammatory disease characterized by endothelial dysfunction, oxidative stress, lipid accumulation, and vascular inflammation, leading to cardiovascular events such as myocardial infarction and stroke. Increasing evidence suggests that dietary polyphenols may offer cardioprotective benefits by targeting key molecular pathways involved in atherogenesis. This narrative review summarizes current evidence on the mechanisms and therapeutic potential of dietary polyphenols in the prevention and management of atherosclerosis. Published experimental, clinical, and epidemiological studies were evaluated to assess the effects of antioxidants and dietary polyphenols on atherosclerosis. Evidence indicates that polyphenols, including resveratrol, quercetin, catechins, curcumin, and anthocyanins, influence redox homeostasis and LDL oxidation while modulating molecular signaling pathways involved in inflammation, lipid metabolism, endothelial function, and cellular stress responses. These compounds also modulate inflammatory signaling pathways, particularly nuclear factor-kappa B (NF-κB) and MAPK, reducing the expression of adhesion molecules and pro-inflammatory cytokines. Clinical studies and meta-analyses suggest potential improvements in endothelial function, lipid profiles, blood pressure, and inflammatory biomarkers following polyphenol-rich dietary interventions, although findings remain heterogeneous and are largely based on surrogate outcomes. Emerging nano-delivery systems and gut microbiota-targeted approaches may improve polyphenol bioavailability and therapeutic potential, but their clinical efficacy remains to be established. Overall, antioxidants and dietary polyphenols may provide complementary approaches for cardiovascular risk reduction; however, their clinical efficacy in atherosclerosis management remains uncertain. Further well-designed, long-term clinical studies are needed to clarify their therapeutic relevance, optimal dosing, and safety.