Identifying the Antiplatelet Compounds of Garlic Ex Vivo

描述（由申请人提供）：背景：在9项对照和6项非对照临床试验中，合理剂量的大蒜和一些大蒜产品/补充剂的潜在抗血小板活性已经在体外得到了相当好的证实。如果不确定造成这种效果的主要活性化合物，就无法进一步确定这种效果，因为（1）由于品种，生长环境，甚至收获日期，大蒜鳞茎中存在适度大的天然成分变化，（2）在大蒜补充剂的类型和品牌中发现非常大的成分变化。为了相关，活性化合物/类别必须在离体而不是体外条件下鉴定。目的：本研究的主要目的是鉴定和量化大蒜（压碎的大蒜）中具有体外抗血小板活性的主要化合物类别。次要目的是（1）确定使用聚集仪和血小板功能分析仪（PFA）监测活性的最佳离体条件，（2）确定大蒜化合物/组分之间的任何相互作用，以及（3）通过对血浆血栓素[和前列环素]的影响研究作用机制。设计图：在急性研究中，将制备八种化学成分明确的大蒜组分，并将其抗血小板活性与食用4-8 g压碎的大蒜制剂的抗血小板活性进行比较。这些组分将以类似于其在压碎的大蒜中的含量的剂量食用。如果确定PFA比全血阻抗聚集测定法更合适，则将使用PFA监测抗血小板活性。含义：因为抗血小板活性在预防心脏病方面是公认的，并且因为大蒜和大蒜补充剂通常用于心血管益处，所以大蒜的主要抗血小板化合物的鉴定可以通过以下方式改善人类健康：（1）使确定最佳品种和生长/收获条件成为可能，这将导致抗血小板化合物的最大水平，（2）通过使用已知活性化合物水平的大蒜产品来提高未来抗血小板活性临床试验的质量，以及（3）为使心血管健康声明的大蒜补充剂标准化提供适当的基础。

DESCRIPTION (provided by applicant): Background: The potential antiplatelet activity of reasonable doses of garlic and some garlic products/ supplements has been fairly well established ex vivo in 9 controlled and 6 uncontrolled clinical trials. Further progress into establishing the effect cannot be made without identifying the main active compounds responsible for the effect because of (1) the moderately large natural compositional variation found among garlic bulbs due to variety, growth environment, and even harvest date and (2) the very large compositional variation found among types and brands of garlic supplements. To be relevant, the active compounds/classes must be identified under ex vivo, rather than in vitro, conditions. Aims: The primary aim of the study will be to identify and quantify the main classes of compounds in garlic (crushed garlic) with ex vivo antiplatelet activity. Secondary aims will be to (1) determine the optimum ex vivo conditions for monitoring activity using both an aggregometer and a platelet function analyzer (PFA), (2) establish any interactive effects between the garlic compounds/fractions, and (3) investigate the mechanism of action via effects on plasma thromboxane [and prostacyclin]. Design: In acute studies, eight chemically defined fractions of garlic will be prepared and their antiplatelet activity compared to that of consuming 4-8 g of a crushed garlic preparation. The fractions will be consumed at a dose similar to their content in crushed garlic. Antiplatelet activity will be monitored by use of the PFA, if determined to be more appropriate than whole blood impedance aggregometry. Implications: Because antiplatelet activity is well-established in the prevention of heart disease and because garlic and garlic supplements are commonly consumed for cardiovascular benefits, identification of the main antiplatelet compounds of garlic may improve human health by (1) making it possible to determine the best varieties and growing/harvesting conditions that will result in maximum levels of antiplatelet compounds, (2) improving the quality of future clinical trials on antiplatelet activity through use of garlic products of known levels of active compounds, and (3) providing a proper basis for standardization of garlic supplements making cardiovascular health claims.