α-Bulnesene, a novel PAF receptor antagonist isolated from Pogostemon cablin
α-Bulnesene, a novel PAF receptor antagonist isolated from Pogostemon cablin
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DOI：
10.1016/j.bbrc.2006.05.006
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发表时间：
2006-07-07
影响因子：
3.1
通讯作者：
Tsai, Ying-Chieh
中科院分区：
文献类型：
--
作者：
Hsu, Hui-Chun;Yang, Wen-Chia;Tsai, Ying-Chieh
α-布尔尼烯是从广藿香的水提取物中分离的倍半萜类化合物。对血小板活化因子（PAT）和花生四烯酸（AA）诱导的家兔血小板聚集有明显的抑制作用，并呈浓度依赖性。在PAF受体的放射性配体结合试验中，α-布呢烯竞争性抑制[H-3]PAF与PAY受体的结合，IC 50值为17.62 +/- 5.68 μ M。α-布尔尼烯还剂量依赖性地抑制负载fluo-3/AM的血小板中PAF诱导的细胞内Ca 2+增加（IC 50值为19.62 +/- 1.32 μ M）。α-布呢烯还能抑制AA诱导的血栓素B 2（TXB 2）和前列腺素E 2（PGE 2）的生成。这些结果表明，α-布呢烯对血小板聚集的抑制作用是由于双重活性;特别是化学阻断PAF诱导的细胞内信号转导和干扰环氧合酶活性，这导致血栓素形成减少。本研究首次证明α-布呢烯是PAT受体拮抗剂以及抗血小板聚集剂。(c)2006爱思唯尔公司All rights reserved.
alpha-Bulnesene is a sesquiterpenoid isolated from the water extract of Pogosternon cablin. It showed a potent and concentration-dependent inhibitory effect on platelet-activating factor (PAT) and arachidonic acid (AA) induced rabbit platelet aggregation. In a radioligand binding assay for the PAF receptor, alpha-bulnesene competitively inhibited [H-3]PAF binding to the PAY receptor with an IC50 value of 17.62 +/- 5.68 mu M. alpha-Bulnesene also dose-dependently inhibited PAF-induced intracellular Ca2+ increase in fluo-3/AM-loaded platelets (IC50 values of 19.62 +/- 1.32 mu M). Furthermore, alpha-bulnesene inhibited AA-incluced thromboxane B-2 (TXB2) formation and prostaglandin E-2 (PGE(2)) formation. These results indicate that the inhibitory effect of alpha-bulnesene on platelet aggregation was due to a dual activity; specifically the chemical blocked PAF-induced intracellular signal transduction and interfered with cyclooxygenase activity, which resulted in a decrease in thromboxane formation. This study is the first to demonstrate that alpha-bulnesene is a PAT receptor antagonist as well as an anti-platelet aggregation agent. (c) 2006 Elsevier Inc. All rights reserved.