Identifying the Antiplatelet Compounds of Garlic Ex Vivo

背景：合理剂量的大蒜和一些大蒜制品/补充剂的潜在抗血小板活性已经在9个对照和6个非对照临床试验中得到了相当好的验证。如果不确定产生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、甚至收获日期的不同，大蒜鳞茎中的天然成分差异适中；(2)大蒜补充剂的种类和品牌之间的成分差异很大。为了具有相关性，活性化合物/类别必须在离体而不是体外条件下进行鉴定。目的：本研究的主要目的是鉴定和定量大蒜（碎大蒜）中具有体外抗血小板活性的主要化合物类别。次要目标将是：(1)使用聚集计和血小板功能分析仪（PFA）确定监测活性的最佳离体条件，(2)确定大蒜化合物/馏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：在急性研究中，将制备8种化学定义的大蒜组分，并将其抗血小板活性与食用4-8克碎大蒜制剂进行比较。这些馏分将以与其在碎大蒜中的含量相似的剂量被食用。如果确定PFA比全血阻抗聚集法更合适，则使用PFA监测抗血小板活性。含义:由于抗血小板活性在预防心脏病方面已得到证实，并且由于大蒜和大蒜补充剂通常被用于心血管健康，因此确定大蒜的主要抗血小板化合物可能通过以下方式改善人类健康：(1)使确定最佳品种和种植/收获条件成为可能，从而产生最大水平的抗血小板化合物；(2)通过使用已知活性化合物水平的大蒜产品，提高未来抗血小板活性临床试验的质量；(3)为大蒜补充剂的标准化提供适当的依据，使其具有心血管健康功效。

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.