Hydroxychavicol, a novel betel leaf component, inhibits platelet aggregation by suppression of cyclooxygenase, thromboxane production and calcium mobilization
Hydroxychavicol, a novel betel leaf component, inhibits platelet aggregation by suppression of cyclooxygenase, thromboxane production and calcium mobilization
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DOI：
10.1038/sj.bjp.0707367
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发表时间：
2007-09-01
影响因子：
7.3
通讯作者：
Jeng, J. H.
中科院分区：
文献类型：
--
作者：
Chang, M. C.;Uang, B. J.;Jeng, J. H.
背景与目的：血小板功能亢进在心血管疾病的发病机制中占有重要地位。槟榔叶（PBL）被世界上2亿至6亿槟榔咀嚼者消耗。实验方法：观察槟榔叶提取物羟基胡椒酚（HC）对血小板聚集、血栓素B-2（TXB 2）和活性氧（ROS）产生、环氧合酶（考克斯）活性、离体血小板聚集、小鼠出血时间和体内血小板栓形成的影响。结果表明：HC能抑制花生四烯酸（AA）和胶原诱导的血小板聚集和TXB_2的产生。HC可抑制凝血酶诱导的TXB_2生成，但不抑制血小板聚集。SQ 29548抑制胶原和凝血酶诱导的TXB 2产生，但不抑制凝血酶诱导的血小板聚集。HC还抑制考克斯-1/考克斯-2酶活性以及AA诱导的ROS产生和Ca 2+动员。HC进一步抑制离体富血小板血浆的血小板聚集（> 100 nmole/小鼠）和延长肠系膜微血管中的血小板栓形成（> 300 nmole/小鼠），但对小鼠尾部出血时间几乎没有影响。结论：HC是一种有效的考克斯-1/考克斯-2抑制剂，能清除ROS，抑制血小板钙信号、TXB 2的生成和聚集。HC通过其抗炎和抗血小板作用，可能成为预防和治疗动脉粥样硬化和其他心血管疾病的潜在治疗药物，而不影响止血功能。
Background and purpose: Platelet hyperactivity is important in the pathogenesis of cardiovascular diseases. Betel leaf (PBL) is consumed by 200-600 million betel quid chewers in the world. Hydroxychavicol (HC), a betel leaf component, was tested for its antiplatelet effect.Experimental approach: We tested the effect of HC on platelet aggregation, thromboxane B-2 (TXB2) and reactive oxygen species (ROS) production, cyclooxygenase (COX) activity, ex vivo platelet aggregation and mouse bleeding time and platelet plug formation in vivo. The pharmacokinetics of HC in rats was also assessed.Key results: HC inhibited arachidonic acid (AA) and collagen-induced platelet aggregation and TXB2 production. HC inhibited the thrombin-induced TXB2 production, but not platelet aggregation. SQ29548, suppressed collagen- and thrombin-induced TXB2 production, but not thrombin-induced platelet aggregation. HC also suppressed COX-1/COX-2 enzyme activity and the AA-induced ROS production and Ca2+ mobilization. HC further inhibited the ex vivo platelet aggregation of platelet-rich plasma ( > 100 nmole/mouse) and prolonged platelet plug formation ( > 300 nmole/mouse) in mesenteric microvessels, but showed little effect on bleeding time in mouse tail. Moreover, pharmacokinetics analysis found that more than 99% of HC was metabolized within 3 min of administration in Sprague-Dawley rats in vivo.Conclusions and implications: HC is a potent COX-1/COX-2 inhibitor, ROS scavenger and inhibits platelet calcium signaling, TXB2 production and aggregation. HC could be a potential therapeutic agent for prevention and treatment of atherosclerosis and other cardiovascular diseases through its anti-inflammatory and antiplatelet effects, without effects on haemostatic functions.