Inhibition of Cholesterol Synthesis by Green and Black Tea

描述（由申请人提供）：“功能食品”、草药和其他植物产品以及营养补充剂作为治疗慢性和急性疾病的安全有效的手段受到公众的广泛欢迎。由于高胆固醇血症是一个普遍存在的问题，人们对替代药物非常感兴趣，红茶降低血清胆固醇水平的能力尤其令人感兴趣。同样，在动物实验中，绿茶也被证明具有降低胆固醇的作用。这些安全且广泛消费的饮料降低胆固醇的机制尚未被阐明。虽然目前大多数证据表明茶多酚减少饮食和胆道胆固醇的吸收，但我们最近对肝癌细胞的研究表明，绿茶和红茶提取物也通过直接酶抑制和抑制HMG-CoA还原酶活性来减少胆固醇合成。了解饮茶如何降低胆固醇水平对于理解其摄入的益处和潜在的不利影响至关重要，特别是与处方药（包括抑制HMG-CoA还原酶的胆固醇合成的他汀类药物）联合使用时。由于我们目前的研究表明，茶提取物引起amp激酶的激活以抑制HMG-CoA还原酶的活性，本应用的目的是确定茶提取物是否直接激活amp激酶，或者是否涉及上游信号通路；并确定茶是否能抑制体内胆固醇的合成。这些研究应该描述茶化合物抑制胆固醇合成的细胞内机制，并阐明抑制胆固醇合成在多大程度上有助于绿茶和红茶的降胆固醇作用。这些研究应该对茶如何减少胆固醇合成和降低血液胆固醇水平建立一个坚实的机制理解，并且，鉴于对amp激酶在糖尿病中的作用的不断认识，也可能为糖尿病和“代谢综合征”的管理开辟新的途径。

DESCRIPTION (provided by applicant): "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".