Inhibition of Cholesterol Synthesis by Green and Black Tea

绿茶和红茶抑制胆固醇合成

基本信息

批准号：
7883660
负责人：
TODD D PORTER
金额：
$ 21.6万
依托单位：
UNIVERSITY OF KENTUCKY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-01 至 2013-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7883660
关键词：
5&apos -AMP-activated protein kinase Acute Disease Adverse effects Alternative Medicine Animals Antibodies Beverages Biliary Biological Assay Black Tea Blood Botanicals Cells Cholesterol Cholesterol Synthesis Inhibition Chronic Consumption Cyclic AMP-Dependent Protein Kinases Deacetylase Diabetes Mellitus Dose Enzyme Activation Enzyme Inhibition Enzymes Green tea Hepatic Hydroxymethylglutaryl-CoA reductase Immunoblotting Intake Knowledge LDL Cholesterol Lipoproteins Lead Liver Measures Mediating Metabolic syndrome Monitor Mus Oral Pathway interactions Pharmaceutical Preparations Pharmacologic Substance Phosphorylation Phosphotransferases Preparation Protein Kinase Research Resveratrol Role STK11 gene Serum Signal Pathway Small Interfering RNA Solid Sterols Tea Water absorption adenylate kinase diabetes management dietary supplements functional food hepatoma cell hypercholesterolemia in vivo interest knock-down man polyphenol upstream kinase

项目摘要

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".

描述（由申请人提供）：“功能性食品”，草药和其他植物产品以及营养补品在公众中广受欢迎，作为治疗慢性和急性疾病的安全有效手段。由于高胆固醇血症是一个普遍的问题，人们对替代药物产生了极大的兴趣，因此特别有趣的是，红茶降低血清胆固醇水平的能力尤其令人感兴趣。同样，在动物研究中，绿茶已被证明是降胆固醇的。这些安全而广泛消费的饮料对降低胆固醇的作用的机制尚未阐明。尽管目前的大多数证据表明，茶多酚降低了饮食和胆汁胆固醇的吸收，但我们最近对肝癌细胞的研究表明，绿色和红茶提取物也通过直接酶抑制和通过抑制HMG-COA还原酶活性来降低胆固醇的合成。了解茶消耗如何降低胆固醇水平对于了解其摄入的益处和潜在不利影响至关重要，尤其是与包括他汀类药物在内的处方药结合使用，这些药物类似地抑制了HMG-COA还原酶的胆固醇合成。由于我们目前的研究表明，茶提取物导致AMP激酶激活抑制HMG-COA还原酶活性，因此本应用的目标是确定茶提取物是否直接激活AMP激酶，还是涉及上游信号通路；并确定茶是否抑制体内胆固醇的合成。这些研究应描述茶化合物抑制胆固醇合成的细胞内机制，并阐明胆固醇合成的抑制程度有助于绿茶的降胆固醇效果。这些研究应该对茶的降低胆固醇合成并降低血液胆固醇水平的方式建立坚实的机械理解，并且考虑到对AMP-激酶在糖尿病中的作用的发展，也可能为治疗糖尿病和“代谢综合征”的治疗开放新途径。