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Grant Abstract

Grant Number: 1R21AT005235-01

Abstract: "Functional foods", herbal and other botanical products, and nutritional supplements have gained great popularity among the public as safe and effective means to treat chronic and acute diseases. As hypercholesterolemia is a widespread problem for which there is great interest in alternative medicines, the demonstrated ability of black tea to decrease serum cholesterol levels is of particular interest. Similarly, green tea has been shown to be hypocholesterolemic in animal studies. The mechanism by which these safe and widely consumed beverages act to lower cholesterol has not yet been elucidated. Although most current evidence indicates that tea polyphenols reduce the absorption of dietary and biliary cholesterol, our recent studies with hepatoma cells indicate that green and black tea extracts also decrease cholesterol synthesis via both direct enzyme inhibition and by suppression of HMG-CoA reductase activity. Knowledge of how tea consumption lowers cholesterol levels is essential to understanding the benefits and potential adverse effects of its intake, particularly in combination with prescription pharmaceuticals, including the statin drugs, which similarly inhibit cholesterol synthesis at HMG-CoA reductase. As our current studies indicate that tea extracts cause the activation of AMP-kinase to suppress HMG-CoA reductase activity, the objectives of this application are to determine if tea extracts directly activate AMP-kinase, or if upstream signaling pathways are involved; and to determine if tea suppresses cholesterol synthesis in vivo. These studies should delineate the intracellular mechanism by which tea compounds suppress cholesterol synthesis, and elucidate the extent to which suppression of cholesterol synthesis contributes to the hypocholesterolemic effect of green and black tea. These studies should establish a solid, mechanistic understanding of how tea decreases cholesterol synthesis and lowers blood cholesterol levels, and, given the developing recognition of the role of AMP-kinase in diabetes, may also open new pathways to the management of diabetes and "metabolic syndrome".

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