Supplementation with Cyanidin-3-O-ß-Glucoside Protects against Hypercholesterolemia-Mediated Endothelial Dysfunction and Attenuates Atherosclerosis in Apolipoprotein E–Deficient Mice

Abstract

In this study, we investigated the protective effects of the anthocyanin cyanidin-3-O-β-glucoside (C3G) on hypercholesterolemia-induced endothelial dysfunction in apoE-deficient (apoE(-/-)) mice. In the prevention study, twenty 8-wk-old male apoE(-/-) mice (n = 10/group) were fed a high-fat, cholesterol-rich diet (HCD) or the HCD supplemented with C3G (2 g/kg diet) for 8 wk. The endothelium-dependent relaxation response to acetylcholine in the aortas of the C3G-fed mice was greater compared with those fed the HCD (P < 0.05). The atherosclerotic plaque area in the aortic sinus of mice fed the C3G diet was lowered by 54% compared with those fed the HCD (P < 0.01). Mice fed C3G had greater expression of the ATP-binding cassette transporter G1 (ABCG1) and lower cholesterol, mainly 7-ketocholesterol (7-KC), concentrations than those fed the HCD. Superoxide production and lipid hydroperoxides in aorta were lower in mice fed C3G compared with those fed the HCD. The phosphorylation levels at Ser1177 of endothelial NO synthase (eNOS) and the production of cyclic GMP (cGMP) in aorta were greater in C3G-fed mice than in HCD-fed mice. In the therapy study, apoE(-/-) mice were fed the HCD for 8 wk and then continued to receive the HCD or were switched to the HCD supplemented with C3G (2 g/kg diet) for another 8 wk. The established endothelial dysfunction and atherosclerosis were reversed, accompanied by greater ABCG1 expression in aorta, lower cholesterol and 7-KC concentrations, and greater generation of cGMP in mice fed C3G compared with those fed the HCD. Taken together, our results show that the anthocyanin C3G prevents or reverses hypercholesterolemia-induced endothelial dysfunction by inhibiting cholesterol and 7-oxysterol accumulation in the aorta and the subsequent decrease in superoxide production, thereby preserving eNOS activity and NO bioavailability.

Anthocyanin increases adiponectin secretion and protects against diabetes-related endothelial dysfunction

“…After several washouts, phenylephrine (1 M) was used to produce a steady contraction, and acetylcholine (ACh, an endothelium-dependent vasodilator, 10 Ϫ9 to 10 Ϫ5 M) was added cumulatively to induce endothelium-dependent relaxation. Endothelium-independent relaxation was stimulated in aortic rings with sodium nitroprusside (SNP, an endothelium-independent nitric oxide-releasing agent, 10 Ϫ9 to 10 Ϫ5 M), and the vascular relaxation was recorded (41). Adenoviral vectors and infection.…”

“…Many studies have focused on cyanidin-3-O-␤-glucoside (C3G), the best known and most investigated anthocyanin (13,16,45). Our previous studies have shown that dietary supplementation with C3G enhanced endothelium-dependent vasorelaxation and inhibited atherogenesis in hypercholesterolemic apoE Ϫ/Ϫ mice (41); the underlying mechanism may be associated with the induction of oxysterol efflux from endothelial cells by anthocyanin (42). Furthermore, we also reported that C3G intake significantly improved insulin sensitivity in both diet-induced and genetic animal models of type 2 diabetes (11); however, both the impact of C3G on vascular function in diabetes and the molecular mechanism that confers vascular protection are poorly understood.…”

Anthocyanin-rich Phytochemicals from Aronia Fruits Inhibit Visceral Fat Accumulation and Hyperglycemia in High-fat Diet-induced Dietary Obese Rats

“…showed that cyanidin 3-glucoside reduced hyperlipidemia in rats 16 and Quin et al reported that chokeberry extracts attenuated epididymal adipose tissue accumulation in rats fed a fructose-rich diet 17 . Antiobesity properties of chlorogenic acid and proanthocyanidin, constituents of aronia phytochemicals, have also been reported 18 21 .…”

Action mechanism and cardiovascular effect of anthocyanins: a systematic review of animal and human studies

“…In the same year, Wang et al [163] used two treatment models to investigate the effect of C3G on endothelial dysfunction and atherogenesis in Apo E-deficient animals. In the prevention model, the animals were treated with doses of C3G (2 g/kg) and a cholesterol-rich diet during 8 weeks.…”