Oxidative stress and inflammation play a pivotal role in the initiation and progression of atherosclerosis and CVD.58,59
Several lines of evidence indicate a role for berry anthocyanins in significantly decreasing oxidative damage and inflammation in cellular and animal models of CVD. Youdim et al. have reported the incorporation of elderberry anthocyanins by endothelial cells, following a 4-h incubation at a concentration of 1 mg/mL. In addition to the cellular bioavailability, elderberry anthocyanins significantly decreased cytotoxicity caused by chemical inducers of oxidative stress.60
Anthocyanins from blackberry extract were shown to protect against peroxynitrite-induced oxidative damage in human umbilical vein endothelial cells.61
Mulberry anthocyanins have also exhibited antioxidative and antiatherogenic affects, by inhibiting oxidation of LDL and formation of foamcells, respectively, in an in vitro model of atherosclerosis.62
Anthocyanins from berries commonly consumed in the United States, such as blueberries and cranberries, have been reported to reduce TNF-α induced upregulation of inflammatory mediators in human microvascular endothelial cells.63
In an 8-week study, DeFuria et al. have shown the attenuation of inflammatory gene expressions in male C57Bl/6j mice fed a high-fat diet supplemented with blueberry powder versus the unsupplemented group. This study also showed the protective effects of blueberries against insulin resistance and hyperglycemia, thus reducing the risk factors for CVD.64
In a rat model of prediabetes and hyperlipidemia, Jurgoski et al.65
further demonstrated decreased activities of inńtestinal mucosal disaccharidases (maltase and sucrose) following dietary supplementation with chokeberry fruit extract for 4 weeks. These animal and in vitro data show the potential of berries to ameliorate inflammation, glucose, and lipid abnormalities that contribute to CVD.
Nitric oxide (NO), when formed through activation of inducible nitric oxide synthase (iNOS), has proinflammatory effects, leading to increased vascular permeability, induction of inflammatory cytokines, and the formation of peroxynitrite, a strong oxidizing agent.66
Pergola et al. have reported inhibitory effects of the anthocyanin fraction of blackberry extract on NO biosynthesis in the murine monocyte/macrophage J774 cell line stimulated with lipopolysaccharide. The study also reported that blackberry anthocyanin extract inhibited inducible iNOS protein expression, thereby decreasing the inflammatory response in macrophages and inhibiting the formation of foam cells.67
While increased iNOS expression leads to the proinflammatory effects of NO, generation of NO by endothelial nitric oxide synthase (eNOS) plays a crucial role in maintaining cardiovascular homeostasis by favorably modulating blood pressure and reducing endothelial dysfunction. Xu et al. and Lazze et al. have reported the upregulation of eNOS by cyanidin-3-glucoside in bovine artery endothelial cells, and increased protein levels of eNOS by anthocyanin treatment (cyanidin and delphinidin) in human umbilical vein endothelial cells.68,69
Berry anthocyanins have also been shown to affect lipid metabolism in cellular and animal models of dyslipidemia. Administration of chokeberry juice for 30 days in rats fed a standard or 4% cholesterol-containing diet, showed the anti-hyperlipidemic effects of chokeberry juice in the cholesterol-fed group.70
Purified anthocyanins from blueberries and strawberries added to drinking water were shown to prevent the development of dyslipidemia and obesity in mice fed a high-fat diet for a period of 90 days.71
Anthocyanin treatment of human umbilical vein endothelial cells was further demonstrated to regulate cholesterol distribution by interfering with the recruitment of tumor necrosis factor receptor-associated factors (TRAF)-2 in lipid rafts, thereby inhibiting CD40-induced proinflammatory signaling.72
Thus, on the basis of these data, berry anthocyanins may exert cardioprotective effects by reducing oxidative stress and inflammation through effects on iNOS activity, interfering with carbohydrate digestion and reducing glucose absorption, favorably modulating dyslipidemia, and upregulating eNOS expression so as to maintain normal vascular function and blood pressure.