Li Guangming, Butz Daniel, Dong Baiyan, Park Yeonhwa, Pariza Michael W, Cook Mark E
Molecular and Environmental Toxicology, University of Wisconsin-Madison, 53706, USA.
Eur J Pharmacol. 2006 Sep 18;545(2-3):93-9. doi: 10.1016/j.ejphar.2006.06.059. Epub 2006 Jun 29.
Conjugated linoleic acids have been shown to reduce eicosanoid release from select tissues and/or cells. To elucidate effects of conjugated linoleic acid isomers on cyclooxygenase-1 (COX-1) activity and their application as platelet aggregation inhibitors, conjugated linoleic acid isomers and conjugated nonadecadienoic acid were incubated with ovine COX-1 and Raw264.7 macrophage to examine their effects on COX-1 activity. The effects were further examined in collagen and ADP-induced guinea pig whole blood platelet aggregation. Fatty acids tested were shown to inhibit COX-1 enzymatic activity. However, only 10t, 12c-conjugated linoleic acid, 9t, 11t-conjugated linoleic acid and conjugated nonadecadienoic acid inhibited collagen and ADP-induced platelet aggregation with IC(50) 125.9 microM (74.2 microM to 213.4 microM, 95% confidence interval), 99.3 microM (52.8 microM to 187.2 microM, 95% confidence interval) and 124.3 microM (85.1 microM to 181.5 microM, 95% confidence interval) respectively in collagen-induced aggregation. TxB(2) release was also appreciably inhibited by 10t, 12c-conjugated linoleic acid, 9t, 11t-conjugated linoleic acid and conjugated nonadecadienoic acid. Based on these data, we conclude 10t, 12c-conjugated linoleic acid, 9t, 11t-conjugated linoleic acid and conjugated nonadecadienoic acid are platelet aggregation inhibitors while 9c, 11t-conjugated linoleic acid is a moderate inhibitor and linoleic acid, and 9c, 11c-conjugated linoleic acid have no effect on whole blood platelet aggregation.
共轭亚油酸已被证明可减少特定组织和/或细胞中类花生酸的释放。为了阐明共轭亚油酸异构体对环氧合酶-1(COX-1)活性的影响及其作为血小板聚集抑制剂的应用,将共轭亚油酸异构体和共轭十九碳二烯酸与绵羊COX-1和Raw264.7巨噬细胞一起孵育,以检测它们对COX-1活性的影响。在胶原蛋白和ADP诱导的豚鼠全血血小板聚集中进一步检测了这些影响。所测试的脂肪酸显示出抑制COX-1酶活性的作用。然而,只有10t, 12c-共轭亚油酸、9t, 11t-共轭亚油酸和共轭十九碳二烯酸抑制胶原蛋白和ADP诱导的血小板聚集,在胶原蛋白诱导的聚集中其IC(50)分别为125.9微摩尔(74.2微摩尔至213.4微摩尔,95%置信区间)、99.3微摩尔(52.8微摩尔至187.2微摩尔,95%置信区间)和124.3微摩尔(85.1微摩尔至181.5微摩尔,95%置信区间)。10t, 12c-共轭亚油酸、9t, 11t-共轭亚油酸和共轭十九碳二烯酸也显著抑制了血栓素B2(TxB(2))的释放。基于这些数据,我们得出结论,10t, 12c-共轭亚油酸、9t, 11t-共轭亚油酸和共轭十九碳二烯酸是血小板聚集抑制剂,而9c, 11t-共轭亚油酸是中度抑制剂,亚油酸和9c, 11c-共轭亚油酸对全血血小板聚集没有影响。