Optimizing Therapeutic Ratios for Herbs

据估计，美国有12%的成年人使用草药。银杏是使用最广泛的草药之一，去年的销售额超过9000万美元。银杏传统上被认为可以改善血液循环，尤其是大脑循环，它被用来提高认知能力和改善外周循环。最近的临床试验表明，早期阿尔茨海默病患者的认知能力改善应该增加老年人银杏的使用。然而，使用它可能不是没有风险的。医学文献中有几个案例报道了银杏使用与严重风险之间的联系。医学文献中有几例关于银杏与严重出血相关的病例报告，在人类和动物身上的研究证实，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存在相互作用。在阿司匹林的情况下，相互作用可能是由于联合对血小板聚集的直接作用，但与其他药物在细胞色素P450系统水平上的相互作用是可能的。本提案的目的是研究银杏是否可能与华法林和噻氯匹定等处方抗凝剂在细胞色素P450系统水平上相互作用。进一步的研究将确定银杏的哪些部分具有抗血小板作用，以及这些部分如何与银杏的非特异性抗氧化作用相关，这可能被认为是银杏有益的原因。这些组分也将被用于检测其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，草药产品的一致性因产品而异，也因同一产品的批次而异。通过解决草药产品一致性问题，并使用实验室模型来定义潜在临床意义的化学和生物学机制，本提案为常用草药产品的多学科研究提供了一个范例。

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.