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：
7701289
负责人：
TODD D PORTER
金额：
$ 18.14万
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 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7701289
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充剂作为治疗慢性和急性疾病的安全有效的手段而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，因此红茶降低血清胆固醇水平的能力尤其令人感兴趣。同样，动物研究表明绿茶具有降低胆固醇的作用。这些安全且广泛饮用的饮料降低胆固醇的机制尚未阐明。尽管目前大多数证据表明茶多酚会减少膳食胆固醇和胆汁胆固醇的吸收，但我们最近对肝癌细胞的研究表明，绿茶和红茶提取物还可以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了解饮茶的益处和潜在的副作用至关重要，特别是与处方药（包括他汀类药物）结合使用时，他汀类药物同样会抑制 HMG-CoA 还原酶的胆固醇合成。由于我们目前的研究表明，茶提取物会激活 AMP-激酶，从而抑制 HMG-CoA 还原酶活性，因此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；并确定茶是否抑制体内胆固醇合成。这些研究应该阐明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、机制性的理解，而且，鉴于人们对 AMP 激酶在糖尿病中的作用的认识不断加深，这些研究也可能为糖尿病和“代谢代谢”的管理开辟新的途径。综合症”。