Inhibition of Cholesterol Synthesis by Green and Black Tea

描述(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和有效手段，在公众中广受欢迎。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，红茶被证明有能力降低血清胆固醇水平，这一点特别令人感兴趣。同样，在动物实验中，绿茶也被证明是低胆固醇的。这些安全和广泛消费的饮料降低胆固醇的机制尚未阐明。尽管大多数现有证据表明茶多酚可减少饮食和胆汁中胆固醇的吸收，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抑制酶和抑制HMG-CoA还原酶活性来减少胆固醇的合成。了解茶的消费如何降低胆固醇水平，对于了解茶的摄入的好处和潜在的不利影响至关重要，特别是与处方药结合使用时，包括他汀类药物，这些药物类似地抑制HMG-CoA还原酶的胆固醇合成。由于我们目前的研究表明，茶叶提取物引起AMP-激酶的激活，从而抑制HMG-CoA还原酶的活性，本研究的目的是确定茶叶提取物是否直接激活AMP-激酶，或者是否涉及上游信号通路；以及确定TEA是否抑制体内胆固醇的合成。这些研究应该阐明茶类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。这些研究应该建立对茶如何减少胆固醇合成和降低血液胆固醇水平的坚实的、机械性的理解，并且，鉴于人们对AMP-激酶在糖尿病中的作用的逐渐认识，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".