Optimizing Therapeutic Ratios for Herbs

优化草药的治疗比例

• 批准号: 6375446
• 负责人: PETER GOLDMAN
• 金额: $ 18.79万
• 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 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6375446
• 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.

据估计，美国有 12% 的成年人使用草药。银杏叶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，银杏被认为可以改善血液循环，特别是大脑的循环，它既可以用来提高认知能力，也可以改善末梢循环。最近的临床试验表明，银杏可以改善早期阿尔茨海默氏病患者的认知能力，这应该会增加老年人对银杏的使用。然而，使用可能并非没有风险。医学文献包含一些关于银杏使用与严重风险之间关联的病例报告。医学文献中包含一些关于使用银杏与严重出血之间存在关联的病例报告，并且对人类受试者和动物的研究证实，银杏的某些部分会损害正常的凝血功能。临床报告表明银杏与阿司匹林和华法林等处方抗凝剂之间存在相互作用，而动物研究表明银杏与抗血栓药物噻氯匹定之间存在相互作用。就阿司匹林而言，相互作用可能是由于对血小板聚集的直接作用相结合而产生的，但与其他药物的相互作用可能是在细胞色素 P450 系统水平上发生的。本提案的目的是研究银杏是否可能在细胞色素 P450 系统水平上与华法林和噻氯匹定等处方抗凝剂相互作用。其他研究将确定银杏的哪些部分与其抗血小板作用有关，以及这些部分与银杏的非特异性抗氧化作用有何关系，这些作用可能被认为是银杏益处的原因。还将分析这些级分防止氧化应激诱导的胚胎大鼠神经细胞凋亡的能力。该项目还将解决草药产品的一致性问题，我们的初步研究表明，不同产品以及同一产品的不同批次之间存在差异。通过解决草药产品的一致性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，该提案为常用草药产品的多学科研究提供了范例。