Arguably the most critical advancement in the elucidation of factors affecting atherogenesis has been the development of mouse models of atherosclerosis. Among available models, the apolipoprotein E–deficient (apoE−/−) mouse is particularly popular because of its propensity to spontaneously develop atherosclerotic lesions on a standard chow diet. A Medline search reveals over 645 articles dedicated to studies using this reliable and convenient “super” animal model since its inception (Piedrahita JA et al, Proc Natl Acad Sci U S A 1992;89:4471–4475; Plump AS et al, Cell 1992;71:343–353) with a more or less steady increase from year to year. This review will examine our present understanding of the pathology and progression of plaques in this animal and highlight some of the nutritional, pharmacological, and genetic studies that have enhanced this understanding.

Atherosclerosis in the apolipoprotein-E-deficient mouse: a decade of progress.

Anthocyanin supplementation improves serum LDL- and HDL-cholesterol concentrations associated with the inhibition of cholesteryl ester transfer protein in dyslipidemic subjects

Is the in vitro antioxidant potential of whole-grain cereals and cereal products well reflected in vivo?

Dietary polyphenols, including anthocyanins, are suggested to be involved in the protective effects of fruits and vegetables against cancer. However, anticancer effects of peonidin 3-glucoside have not been clearly demonstrated, with only limited studies being available concerning the inhibitory effect of cyanidin 3-glucoside for tumor cell growth. Therefore, in this study, we have isolated and identified the two bioactive compounds, peonidin 3-glucoside and cyanidin 3-glucoside, from Oryza sativa L. indica, to treat various cancer cells. The results showed that, among analyzed cell lines, HS578T was the most sensitive to peonidin 3-glucoside and cyanidin 3-glucoside. Treatment with peonidin 3-glucoside or cyanidin 3-glucoside resulted in a strong inhibitory effect on cell growth via G2/M arrest. Regarding cell cyclerelated proteins, peonidin 3-glucoside treatment resulted in down-regulation of protein levels of cyclin-dependent kinase (CDK)-1, CDK-2, cyclin B1, and cyclin E, whereas cyanidin 3-glucoside could decrease the protein levels of CDK-1, CDK-2, cyclin B1, and cyclin D1. In addition, cyanidin 3-glucoside or peonidin 3-glucoside also induced caspase-3 activation, chromatin condensation, and cell death. Furthermore, anthocyanins from O. sativa L. indica were evidenced by their inhibition on the growth of Lewis lung carcinoma cells in vivo.

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Cyanidin 3-glucoside and peonidin 3-glucoside inhibit tumor cell growth and induce apoptosis in vitro and suppress tumor growth in vivo.

Anthocyanins in cereals.

Apolipoprotein (apo)E-deficient mice were used to study the antiatherogenic effect of black rice pigment fraction (BRF) and the possible mechanisms by which it inhibits atherogenesis. The apoE-deficient mice (n = 45) were randomly divided into three groups and received AIN-93G diet (positive group), AIN-93G with 5 g of black rice pigment fraction/100 g (BRF group) and AIN-93G with 5 g of white rice outer layer fraction/100 g (WRF group) for 16 wk. C57BL/6J mice (n = 15) received AIN-93G and were used as a control group. Blood samples were collected for measurement of lipid concentration, antioxidized LDL antibody and nitric oxide concentration. Livers were extracted for determination of cholesterol concentrations, and aortas were used to determine cholesterol concentrations and inducible nitric oxide synthase protein and mRNA expression. Hearts were used to assess atherosclerotic plaque formation. The apoE-deficient mice fed the black rice pigment fraction diet had 48% (P < 0.01) less atherosclerotic lesion area compared with apoE-deficient mice fed only the AIN-93G diet and 46% (P < 0.01) less lesion area compared with mice fed the white rice outer layer fraction diet. This observation corresponded with significantly (P < 0.05) lower total serum cholesterol, lower liver and aorta cholesterol (P < 0.01) and higher HDL cholesterol (P < 0.05) concentrations and lower (P < 0.05) antioxidized LDL antibody titer in apoE-deficient mice fed the black rice pigment fraction diet compared with positive and WRF groups. Notwithstanding this, mice fed the black rice pigment fraction diet also had lower CD4(+) T lymphocyte expression (P < 0.05) and weaker inducible nitric oxide synthase expression (P < 0.05) compared with mice fed the AIN-93G diet and the white rice outer layer fraction diet, respectively. We concluded that the inhibition of atherosclerotic lesions of the black rice pigment fraction is attributed to the improvement in cholesterol accumulation and reduction in oxidative stress and inflammation.

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Wen Hua Ling

Papers

Supplementation of Diets with the Black Rice Pigment Fraction Attenuates Atherosclerotic Plaque Formation in Apolipoprotein E Deficient Mice