How hesperidin and Hesperetin, as promising food Supplements, combat cardiovascular Diseases: A systematic review from bench to bed
Shakiba Najjar Khalilabad, Amirhossein Mirzaei, Vahid Reza Askari, Ali Reza Mirzaei, Reza Khademi, Vafa Baradaran Rahimi
Abstract
• Hesperidin and hesperetin, natural flavonoids found abundantly in citrus fruits, exhibit promising therapeutic potential in combating various aspects of cardiovascular diseases. • Hesperidin and hesperetin mitigate responses related to inflammation and improve antioxidant levels following acute myocardial infarction, possibly through downregulation of Bcl‑2 and PPAR‑γ expression, and NF-κB signaling cascade. • These flavonoids protect against drug-induced cardiotoxicity, including arsenic trioxide, cisplatin, and doxorubicin. • Hesperidin and hesperetin possess antihypertensive properties by modulating the renin-angiotensin system (RAS), reducing oxidative stress while improving vascular function. • Clinical trials also support the potential benefits of hesperidin and hesperetin supplementation in improving blood pressure, endothelial function, and inflammatory markers. This investigation aims to determine how hesperidin and hesperetin, natural flavonoids found abundantly in citrus fruits, affect cardiovascular diseases. From inception until January 2024, relevant literature was reviewed using a systematic review methodology and databases such as Scopus, PubMed, and Web of Science. Hesperidin and hesperetin counteract atherosclerosis, a key contributor to heart disease, by ameliorating lipid profiles, inhibiting plaque formation, and reducing inflammation. These flavonoids protect against drug-induced cardiotoxicity, safeguarding the heart from injury developed by arsenic trioxide, cisplatin, and doxorubicin. They enhance endothelial function, regulate blood pressure, and counteract oxidative stress. Furthermore, clinical trials also support the potential benefits of hesperidin supplementation in improving blood pressure, endothelial function, and inflammatory markers. This thorough review presents significant evidence advocating the inclusion of hesperidin and hesperetin as supplementary, innovative, and cost-efficient remedies for cardiovascular diseases.