Protective Mechanism of an Anti-Inflammatory Herbal Mix

抗炎草药混合物的保护机制

• 批准号: 6863507
• 负责人: ALI BANAN
• 金额: $ 18.5万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-01 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6863507
• 关键词: alternative medicine; antiinflammatory agents; antioxidants; bioassay; combination chemotherapy; cytoprotection; cytoskeleton; folk medicine; gastrointestinal disorder chemotherapy; human subject; inflammation; inflammatory bowel diseases; medicinal plants; microtubules; nitric oxide synthase; nuclear factor kappa beta; oxidative stress; pharmacokinetics; plant extracts; tissue /cell culture; transfection

DESCRIPTION (provided by applicant): Long-term objective: to show that CAM can benefit patients with inflammatory bowel disease (IBD)-two chronic, life-long relapsing disorders, Crohn's Disease & Ulcerative Colitis. Immediate objective: to see if herbal mixtures reputed to be anti-inflammatory and used by IBD patients are protective in an in vitro model of IBD-monolayers of intestinal cells. Strategy: we will use this model to test herbal effects and mechanisms because of the model's established relevance to oxidative injury, loss of barrier integrity and IBD. Background: using this model we showed that oxidants disrupt the barrier by oxidizing and disrupting the cytoskeleton via NF-kappaB activation and iNOS upregulation. Protection is afforded by agents that counteract this cascade. Our recent pilot data suggest that a mixture of anti-inflammatory herbs that is used by IBD patients, Varcho Veda, protects monolayers against oxidant-induced damage, possibly by counteracting this cascade. Hypotheses: HI: Varcho Veda herbs protect monolayers against oxidant-induced damage. H2: Herbs protect by counteracting the oxidant-induced cascade. Aim #1: To see if herbs protect barrier integrity against oxidant-induced injury and, if so, whether the protection requires protection of cytoskeletal integrity. Aim #2: To see if protection requires inhibition of NF-kappaB activation and iNOS upregulation. In both aims, we will expose monolayers to H202 + herbs, individually or as a mixture identical to that taken by CAM-using IBD patients. Outcomes include barrier & cytoskeletal integrity, protein oxidation, iNOS, NF-kappaB activation, and I-kappaB degradation. In selected experiments, monolayers made of transfected cells will be used to further assess the roles of iNOS and NF-kappaB. Significance: Showing that our herbs protect, and do so via anti-oxidant mechanisms will (i) provide a rationale for a clinical trial for these herbs in IBD patients, (ii) suggest that herbs may work by preventing inflammatory cascades that arise from dysregulation of endogenous signaling mechanisms, (iii) suggest the potential efficacy of anti-oxidant and CAM approaches to IBD. Our monolayer model might provide a rapid, in vitro screen for identifying promising candidate herbs or anti-oxidants that should go on to evaluation in vivo in translational studies of oxidation, cytoskeletal & barrier disruption and inflammation (we recently showed that similar oxidative changes and cytoskeletal damage occur in intestinal mucosa of IBD patients).

描述（由申请人提供）：长期目的：表明CAM可以使炎症性肠病（IBD）患者受益 - 两次慢性，终身复发性疾病，克罗恩病和溃疡性结肠炎。直接目的：查看据称是抗炎和IBD患者使用的草药混合物是否在肠细胞的IBD单层体外模型中具有保护性。策略：由于该模型与氧化损伤，屏障完整性的丧失和IBD的相关性，我们将使用该模型来测试草药效应和机制。背景：使用该模型，我们表明氧化剂通过NF-kappab激活和iNOS上调通过氧化和破坏细胞骨架来破坏屏障。保护由抵消该级联的代理商提供。我们最近的试验数据表明，IBD患者使用的抗炎草药瓦尔乔·吠陀（Varcho Veda）使用的抗炎药的混合物可以通过抵消该级联反应，可保护单层免受氧化剂诱导的损伤。假设：HI：Varcho Veda草药可保护单层免受氧化剂诱导的损伤。 H2：通过抵消氧化剂诱导的级联反应来保护草药。目标＃1：查看草药是否保护屏障的完整性免受氧化剂诱导的损伤，如果是的，则保护是否需要保护细胞骨架完整性。目标＃2：查看保护是否需要抑制NF-kappab激活和iNOS上调。在这两个目标中，我们都将单独或与使用CAM使用IBD患者相同的混合物暴露于H202 +草药中。结果包括屏障和细胞骨架完整性，蛋白质氧化，iNOS，NF-kappab激活和I-kappab降解。在选定的实验中，由转染的细胞制成的单层将用于进一步评估iNOS和NF-kappab的作用。意义：表明我们的草药保护并通过抗氧化剂机制进行（i）将为IBD患者的这些草药提供临床试验的基本原理，（ii）表明草药可以通过防止失调引起的炎症级联反应来起作用。内源信号传导机制（III）表明抗氧化剂和CAM方法对IBD的潜在功效。我们的单层模型可能会提供一个快速的体外筛查，用于鉴定有前途的候选草药或抗氧化剂，这些草药或抗氧化剂应继续在体内进行评估，以在氧化，细胞骨架和屏障破坏和炎​​症的转化研究中进行评估（我们最近表明，相似的氧化变化和细胞骨架骨骼的氧化变化IBD患者的肠粘膜损害发生）。