Evaluation of the Effect of Green Tea Polyphenols on IBD

绿茶多酚对IBD的疗效评价

• 批准号: 7122541
• 负责人: GERALD W DRYDEN
• 金额: $ 15.28万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-15 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7122541
• 关键词: alternative medicine; antiinflammatory agents; antioxidants; clinical research; clinical trials; cytokine; drug screening /evaluation; flavonoids; gastrointestinal disorder chemotherapy; gene expression; human subject; human therapy evaluation; inflammatory bowel diseases; interleukin 1; interleukin 10; interleukin 8; monocyte; nuclear factor kappa beta; patient oriented research; pharmacokinetics; tea; tumor necrosis factor alpha; ulcerative colitis

DESCRIPTION (provided by applicant): Interest in green tea as an agent for improving health and treating disease has increased in both the lay and scientific literature. Green tea consists of several components, with most research focusing on the polyphenol fraction. The green tea polyphenols (GrTP) include (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)- epicatechin-3-gatlate (ECG), and (-)-epigallocatechin-3-gallate (EGCG). Of these, EGCG accounts for greater than 40% of the total polyphenol content. Therapeutic and prophylactic benefits have been attributed to the potent anti-oxidant effects of the polyphenols, including reducing the risk of cancer. GrTP also have potent anti-inflammatory properties. GrTP have proven to be potent inhibitors of nuclear factor-kappa B (NF-kB), a key regutatory factor in the control of intestinal inflammation. Activation of NF-kB can be induced by a variety of stimulatory factors, such as the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-a) or interleukin-1 (IL-1), bacterial endotoxin, or oxidative stress. In unstimulated cells, NF-kB exists as a heterodimer comprised of p65 and p50 subunits, bound to a member of the inhibitor-kB (IkB) family of inhibitory proteins. NF-kB activators induce degradation of IkB by the 26s proteosome, by phosphorylation of two serines in the N-terminal regulatory domain of IkB by IkB kinase (IKK). The liberated NF-kB translocates to the nucleus, binds specific promoter sequences, and induces expression of proinflammatory cytokines. These cytokines are expressed at high levels in chronic inflammatory bowel disease (IBD). IL-1 and TNF-a also activate NF-kB in a positive regulatory loop. This may lead to amplification of the inflammatory response. NF-kB appears to play a significant role in inflammation, and is a likely target for anti-inflammatory therapies. Animal models of inflammation improved with GrTP administration. The scientific portion of this proposal intends to evaluate the use of GrTP in humans. Specific aim 1 will confirm that GrTP inhibit NF-kB activation in human peripheral blood monocytes. Specific aim 2 will evaluate the safety and tolerability of GrTP in volunteers with quiescent IBD, while defining the pharmacokinetics and pharmacodynamics of GrTP. Specific aim 3 will further evaluate the safety of GrTP in subjects with IBD, while providing preliminary data on the efficacy of this therapy in patients with active ulcerative colitis.

描述（由申请人提供）： 在外行文献和科学文献中，对绿茶作为改善健康和治疗疾病的代理人的兴趣都在增加。绿茶由几个组成部分组成，大多数研究都集中在多酚部分。绿茶多酚（GRTP）包括（ - ） - epicatechin（ec），（ - ） - epigallocatechin（egc），（ - ） - epicatechin-3-gatlate（ECG）（ECG）和（ - ） - epigallocatechin-3-gallate（ EGCG）。其中，EGCG占多酚总含量的40％以上。治疗和预防性益处归因于多酚的有效抗氧化作用，包括降低癌症的风险。 GRTP还具有有效的抗炎特性。事实证明，GRTP是核因子-KAPPA B（NF-KB）的有效抑制剂，这是控制肠炎的关键再生因素。 NF-KB的激活可以由多种刺激因子诱导，例如促炎性细胞因子肿瘤坏死因子 - α（TNF-A）或白介素-1（IL-1），细菌性内毒素或氧化应激。在未刺激的细胞中，NF-KB作为由p65和p50亚基组成的异二聚体，与抑制剂-KB（IKB）抑制蛋白家族的成员结合。 NF-KB激活剂通过IKB激酶（IKK）在IKB的N末端调节结构域中通过磷酸化的两种丝氨酸诱导IKB降解。解放的NF-KB易位到核，结合特定的启动子序列，并诱导促炎细胞因子的表达。这些细胞因子在慢性炎症性肠病（IBD）中以高水平表达。 IL-1和TNF-A还激活了正调节环中的NF-KB。这可能会导致炎症反应的扩增。 NF-KB似乎在炎症中起着重要作用，并且可能是抗炎疗法的靶标。通过GRTP给药改善了炎症的动物模型。该提案的科学部分旨在评估GRTP在人类中的使用。具体目标1将确认GRTP抑制人外周血单核细胞中的NF-KB激活。具体目标2将评估GRTP在具有静态IBD的志愿者中的安全性和耐受性，同时定义GRTP的药代动力学和药效学。具体目标3将进一步评估IBD受试者GRTP的安全性，同时提供有关该疗法在主动溃疡性结肠炎患者中的有效性的初步数据。