Szewczuk Lawrence M, Penning Trevor M
Department of Biochemistry & Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
J Nat Prod. 2004 Nov;67(11):1777-82. doi: 10.1021/np0498410.
Resveratrol (1) is a m-hydroquinone found in red wine, which has antiinflammatory, cardiovascular protective (antiplatelet), and cancer chemopreventive properties. It is a potent peroxidase-dependent mechanism-based inactivator of COX-1, a desired target for antiplatelet agents, and has no similar effect on COX-2. Much attention has focused on resveratrol (1) as being the sole agent responsible for the cardioprotective effects associated with red wine consumption (commonly known as the "French paradox"). In this study we show that other red wine constituents, namely, the catechins (2, 3) and epicatechins (4, 5), act as peroxidase mediated mechanism-based inactivators of COX-1 but not of COX-2. Structure-activity relationships identify these agents as being as effective as resveratrol with respect to their ability to specifically inactivate COX-1. We show that resorcinol (6) is the minimum structure necessary for mechanism-based inactivation of COX-1. These findings imply that resveratrol is not the sole agent responsible for the antiplatelet activity of red wine and suggest that all dietary m-hydroquinones should be examined for cardioprotective effects.
白藜芦醇（1）是一种存在于红酒中的间苯二酚，具有抗炎、心血管保护（抗血小板）和癌症化学预防特性。它是一种有效的基于过氧化物酶机制的环氧合酶-1（COX-1）失活剂，COX-1是抗血小板药物的理想靶点，而它对环氧合酶-2（COX-2）没有类似作用。白藜芦醇（1）作为与饮用红酒相关的心脏保护作用（通常称为“法国悖论”）的唯一负责药物受到了广泛关注。在本研究中，我们表明红酒中的其他成分，即儿茶素（2,3）和表儿茶素（4,5），可作为基于过氧化物酶介导机制的COX-1失活剂，但不是COX-2的失活剂。构效关系表明这些药物在特异性失活COX-1的能力方面与白藜芦醇一样有效。我们表明间苯二酚（6）是基于机制失活COX-1所需的最小结构。这些发现意味着白藜芦醇不是红酒抗血小板活性的唯一负责药物，并表明应检查所有膳食间苯二酚的心脏保护作用。
