Citrus flavonoids and adhesion molecules: Potential role in the management of atherosclerosis

Atherosclerosis as a chronic inflammatory disorder is accompanied with oxidative stress which causes a high morbidity and mortality. Adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), P-selectin, and E-selectin, are amongst the most important contributors in atherosclerosis. In such cases, dietary interventions with functional foods containing natural antioxidant and anti-inflammatory constituents are of a great interest. Citrus fruits are rich sources of flavonoids as natural pigments with potent antioxidant and anti-inflammatory activities. This study aims to review current evidence regarding the role of citrus flavonoids in the management of atherosclerosis with a focus on their effect on adhesion molecules. Electronic databases including PubMed, Scopus, and Web of Science were searched with the names of adhesion molecules and flavonoids from inception until January 2023. The included articles highly support the beneficial effects of citrus flavonoids in preclinical models of atherosclerosis. Quercetin, naringin and naringenin, hesperidin and hesperetin, nobiletin, rutin, luteolin, apigenin, and kaempferol are the most common flavonoids in citrus fruits which could modulate adhesion molecules including ICAM-1, VCAM-1, E-selectin, and P-selectin. Additionally, markers of chronic inflammation such as interleukins, tumor necrosis factor-alpha, nuclear factor-kappa B, and nitric oxide signaling, as well as oxidative stress markers like superoxide dismutase and glutathione were all normalized upon administration of citrus flavonoids. Conclusively, this review confirms the modulatory role of flavonoids on adhesion molecules in atherosclerosis based on the preclinical evaluations. Thus, citrus fruits can be further studied in atherosclerotic patients regarding their activity in reducing adhesion molecules.