Optimizing Therapeutic Ratios for Herbs

优化草药的治疗比例

• 批准号: 6334338
• 负责人: PETER GOLDMAN
• 金额: $ 23.83万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6334338
• 关键词: Conifera; alternative medicine; anticoagulants; antioxidants; apoptosis; cytochrome P450; dosage; drug interactions; drug screening /evaluation; human tissue; laboratory rat; oxidative stress; plant extracts; warfarin

Herbal remedies are used by an estimated 12% of the adult population in the United States. Ginkbo biloba is one of the most widely used herbs, with sales last year of more than $90 million. Ginkbo has traditionally been thought to improve circulation, particularly to the brain, and it has been used both to increase cognition and to improve peripheral circulation. Recent clinical trial indicating improve cognition in patients with early stage Alzheimer's Disease should increase ginkgo's use among older adults. Use, however, may not be without risk. The medical literature contains several case reports of an association between ginkgo use and severe risk. The medical literature contains several case reports of an association between ginkgo use and severe hemorrhage, and studies in both human subjects and animals confirm that certain fractions of ginkgo impair normal coagulation. Clinical reports suggest an interaction between ginkgo and such prescribed anticoagulants as aspirin and warfarin, while animal studies show3 an interaction with the anti- thrombotic drug ticlopidine. In the case of aspirin the interaction may result from combining direct effects on platelet aggregation, but with the other drugs an interaction at the level of cytochrome P450 system is likely. The goal of this proposal is to investigate is to investigate whether ginkgo may interact with such prescribed anticoagulants as warfarin and ticlopidine at the level of the cytochrome P450 system. Additional studies will determine which fractions of ginkgo are responsible for it anti- platelet effects and how these fractions relate to ginkgo's non-specific antioxidant effects, which may believe are responsible for ginkgo's benefit. Such fractions will also be assayed for their capacity to prevent apoptosis induced in embryonic rat nerve cells by oxidative stress. The project will also address the issue of the consistency of herbal products, which our preliminary studies suggest varies from product to product as well as from to batch of the same product. By addressing the issues of herbal product consistency and using laboratory models to define chemical and biological mechanisms of potential clinical significance, this proposal offers a paradigm for the multi-disciplinary study of commonly used herbal products.

在美国，估计有12％的成年人群使用草药。 Ginkbo Biloba是使用最广泛的草药之一，去年的销售额超过9000万美元。传统上，Ginkbo被认为可以改善循环循环，尤其是对大脑的循环，并且它既被用来增加认知又改善周围循环。最近的临床试验表明，早期阿尔茨海默氏病患者的认知能够提高认知，应增加银杏在老年人中的使用。但是，使用可能不会没有风险。医学文献包含了几例有关银杏使用与严重风险之间关联的病例报告。医学文献包含几例有关银杏使用与严重出血之间存在关联的病例报告，对人类受试者和动物的研究证实了银杏的某些部分会损害正常凝血。临床报道表明银杏与诸如阿司匹林和华法林这样的处方抗凝剂之间的相互作用，而动物研究表明3与抗血栓形成药物质持续惠洛宁的相互作用。在阿司匹林的情况下，相互作用可能是由对血小板聚集的直接作用而引起的，但是对于其他药物，在细胞色素P450系统水平上的相互作用可能是可能的。该提案的目的是调查银杏是否可以与细胞色素P450系统水平上的华法林和ticlopidine等规定的抗凝剂相互作用。其他研究将确定银杏的抗血小板效应的原因是哪些部分，以及这些分数与银杏非特异性抗氧化作用的关系，可能认为这些抗氧化作用可能造成银杏的益处。还将通过氧化应激来预防胚胎大鼠神经细胞诱导的细胞凋亡的能力来测定此类部分。该项目还将解决草药产品一致性的问题，我们的初步研究表明，该产品因产品而异以及同一产品的批次而异。通过解决草药产品一致性的问题，并使用实验室模型来定义具有潜在临床意义的化学和生物学机制，该提案为对常用草药的多学科研究提供了范式。