Apigenin 7‑O‑β‑D‑glucoside is a flavonoid reported as smooth muscle relaxant, anti-inflammatory, and anti-oxidant, suggesting its role in cardiovascular disease. The present study aimed to investigate the effect of apigenin 7‑O‑β‑D‑glucoside on hyperlipidemia and associated vascular dysfunction in rats. Oral administration of apigenin 7‑O‑β‑D‑glucoside to HFD and tyloxopol-induced hyperlipidemic SD rats for 28 and 10 days that reduced significantly (p < 0.01), total cholesterol, LDL, VLDL and triglycerides, and increased HDL levels and also reduced the total body weight and atherogenic index suggesting its antihyperlipidemic effect. This effect was further confirmed when the compound also inhibited the key enzyme HMG-CoA reductase in the biosynthesis of cholesterol. The devastating effects on vascular architecture such as change in the aortic intima, media, adventitia and also the endothelium damage, were reversed in apigenin 7‑O‑β‑D‑glucoside 5 mg/kg/day treated group. In the in vitro studies, the compound reversed the endothelial damage demonstrated by significant vasorelaxation in the aortic rings from hyperlipidemic rats treated with apigenin 7‑O‑β‑D‑glucoside 5 mg/kg/day, with EC₅₀ value of 0.02 μg/mL (0.01-0.20) compared to hyperlipidemic HFD rats, similar to atorvastatin. These findings indicate that antihyperlipidemic effect of apigenin 7‑O‑β‑D‑glucoside is mediated through decrease in total cholesterol, LDL, VLDL, triglyceride level and increase in level of HDL through inhibition of HMG-CoA inhibition and also improved the associated histopathological changes and endothelium dysfunction.

Keywords: Apigenin 7‑O‑β‑D‑glucoside; HFD-induced hyperlipidemia; Lipid profile; HMG-CoA reductase activity; Histopathological study; Vascular function study;