Srivastava K C
Department of Environmental Medicine (ISH), Odense University, Denmark.
Prostaglandins Leukot Essent Fatty Acids. 1993 May;48(5):363-72. doi: 10.1016/0952-3278(93)90116-e.
In continuation of our studies on the oil of cloves--a common kitchen spice and a drug for home medicine--we have isolated and identified two antiplatelet components, eugenol and acetyl eugenol. They inhibited arachidonate-, adrenaline- and collagen-induced platelet aggregation; they were more potent in inhibiting aggregation by the first two agonists. Their inhibitory effect was reversible. These components were antiaggregatory by a combination of at least two effects: (i) inhibition of platelet thromboxane formation, and (ii) increased formation of 12-lipoxygenase products (12-HPETE). Though the presence of plasma proteins would reduce the effective concentration of these substances due to binding, the relatively lower amounts of these components which inhibited arachidonate-induced aggregation when compared to their effects on thromboxane production was intriguing. The answer might partly lie in an increased formation of 12-HPETE facilitated by albumin which acts as a 'conduit' to divert free arachadonic acid (AA) from the platelet cyclooxygenase (CO) to the lipoxygenase pathway (22). Based on their IC50 values, it was found that both eugenol and acetyl eugenol were more potent than aspirin in inhibiting platelet aggregation induced by arachidonate, adrenaline and collagen. In arachidonate-induced aggregation eugenol was on a par with indomethacin. It was found that eugenol and acetyl eugenol when used in combination potentiated inhibition of platelet aggregation induced by arachidonate, adrenaline and collagen. This effect was, however, not evident from the metabolism of AA in platelets; when used in combination the two compounds produced an additive effect.
在我们对丁香精油(一种常见的厨房香料和家庭用药)的研究中,我们分离并鉴定出了两种抗血小板成分,丁香酚和乙酰丁香酚。它们抑制花生四烯酸、肾上腺素和胶原诱导的血小板聚集;对前两种激动剂诱导的聚集抑制作用更强。它们的抑制作用是可逆的。这些成分通过至少两种作用的组合发挥抗聚集作用:(i)抑制血小板血栓素的形成,以及(ii)增加12-脂氧合酶产物(12-HPETE)的形成。尽管血浆蛋白的存在会因结合而降低这些物质的有效浓度,但与它们对血栓素产生的影响相比,这些成分抑制花生四烯酸诱导的聚集所需的量相对较少,这一点很有趣。答案可能部分在于白蛋白促进了12-HPETE的形成增加,白蛋白充当了将游离花生四烯酸(AA)从血小板环氧化酶(CO)转移到脂氧合酶途径的“管道”(22)。根据它们的IC50值,发现丁香酚和乙酰丁香酚在抑制花生四烯酸、肾上腺素和胶原诱导的血小板聚集方面比阿司匹林更有效。在花生四烯酸诱导的聚集中,丁香酚与吲哚美辛相当。发现丁香酚和乙酰丁香酚联合使用时能增强对花生四烯酸、肾上腺素和胶原诱导的血小板聚集的抑制作用。然而,从血小板中AA的代谢情况来看,这种作用并不明显;联合使用时这两种化合物产生相加作用。