3-Hydroxy 3 methylglutaryl coenzyme A reductase (HMG-CoA R) sensitive to mevalonate (or post-mevalonate non-sterol product) regulation but lacking sensitivity to cholesterol feedback regulation is associated with risk of coronary heart disease. Epidemiological studies associate reduced risk of coronary heart disease with increased dietary intakes of fruits, vegetables, legumes and grains. These foods contribute to the diet a broad variety of products of secondary plant metabolism sharing a common precursor, mevalonate. Cataloging plant metabolites which suppress HMG-CoA R activity, the overall goal of this project, is achieved by isolating and identifying effective metabolites from representative plant materials shown in dietary studies to suppress HMG-CoA R. The metabolites are isolated by serial extraction of the plant materials with solvents of increasing polarity, testing of the solvent extracts in dietary studies and chromatographic fractionation of the effective solvent fractions. The chromatographic fractions will be tested in vitro; scaled-up procedures will yield sufficient material for in vivo testing. The effective fractions will be identified using NMR and mass spectrometry. The prospective health impact of the plant metabolites rests on demonstrations of a dietary role in lowering serum low-density lipoprotein cholesterol concentrations when tested in animal models.
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