Identification of functional ingredients of wild rice and their potential mechanisms of maintaining physiologic function and integrity of the vessel wall

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I propose to perform a series of experiments to identify functional ingredients of wild rice and the potential mechanisms by which they may maintain physiologic function and integrity of the vessel wall. In my previous studies, I observed that addition of wild rice to the diets of a genetically-modified mouse model, namely LDL-receptor-KO (LDL-r-KO) mice, was associated with significant reductions in plasma cholesterol levels and maintaining normal morphology of the major coronary arteries and aorta. We know that wild rice contains higher amounts of dietary fiber as compared to the conventional white rice. Dietary fiber may have contributed to the cholesterol-lowering properties of wild rice. However, the extent of reductions in LDL-cholesterol levels was greater than what is expected from dietary fiber per se. Other ingredients of wild rice may have also contributed to the cholesterol-lowering effects and consequently maintaining normal vessel structure and function. I propose to carry out a series of analytical experiments to identify bio-active components of wild rice using the LDL-r-KO and apo E-KO mice as well as appropriate cell lines. I also propose to investigate the impact of long-term consumption of wild rice on the gut micro-flora in these animals. Wild rice may be considered as a prebiotic. Several studies have reported that changes in the type and population of the gut micro-flora may be associated with changes in the formation of biologically active compounds such as short chain fatty acids. These compounds may also beneficially alter cellular lipid metabolism, resulting in reduced serum cholesterol levels. Tissue and plasma samples from these animals will be screened for identification of biologically active substances such as tocopherols, tocotrienols, gamma-oryzanols, ferulic acid and plant sterols. Concentrations of these substances will be correlated with their dietary levels and the state of integrity of the vessel wall plus the biomarkers of inflammation and plasma lipid levels. After establishing the internal doses of the bio-active ingredients of the wild rice, these substances will be tested individually or in combination in both animal models (LDL-r-KO and apo E-KO) mice as well as Hep G2 and Caco-2 cell lines. Additionally, the adhesion of monocytes to the aortic endothelial cells from the treated animals or from the human umbilical vein endothelial cells treated with the test compounds will be tested. The proposed studies will produce data that will shed light on understanding how dietary agents help maintaining the integrity of biological systems; this endorses developing and marketing new functional foods and/or nutraceuticals with a great impact on the Canadian Agriculture and Economy sectors. During this grant, I will train 20 trainees at various levels including undergraduate (10) and graduate (3 PhD + 4 MSc + 2 visiting PhD) students and one post-doctoral fellow.**