高圣草素-7-O-β-D-葡萄糖苷抑制血小板活化因子诱导血小板聚集的机理探讨

高圣草素-7-O-β-D-葡萄糖苷抑制血小板活化因子诱导血小板聚集的机理探讨

管增伟, 王银叶, 杨秀伟, 崔育新

1.北京大学医药卫生分析中心, 北京 100083;
2.北京大学药学院细胞与分子药理学系, 北京 100083;
3.北京大学天然药及仿生药国家重点实验室, 北京 100083

收稿日期:2000-09-01 修回日期:2000-12-09 出版日期:2001-03-15 发布日期:2001-03-15

Homoerydictyl-7-O-β-D-glycoside-A Receptor Antagonist of Platelet-activating Factor (PAF)

Guan Zengwei, Wang Yinye, Yang Xiuwei, Cui Yuxin

1. Medical and Pharmaceutical Analysis Center, Peking University, Beijing 100083;
2. Department of Molecular and Cellular Pharmacology, Peking University School of Pharmaceutical Sciences, Beijing 100083;
3. National Research Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100083

Received:2000-09-01 Revised:2000-12-09 Online:2001-03-15 Published:2001-03-15

摘要/Abstract

摘要： 高圣草素-7-O-β-D-葡萄糖苷是从中草药槲寄生中提取分离的一种黄酮类化合物。已证实该化合物在体内外对血小板活化因子(PAF)诱导的人及兔血小板聚集有明显的抑制作用。本研究应用放射配体[3H]PAF与受体结合的抑制实验证实该化合物是在受体水平上阻断了PAF对血小板的活化作用。抑制呈剂量效应关系, 化合物浓度的负对数与抑制率明显相关(γ = 0.985, P<0.05)。在浓度大于1×10^-5 mol·L^-1时, 增加浓度, 不能提高抑制率, 提示抑制的饱和。抑制的IC50为8×10^-7 mol·L^-1。首次发现,高圣草素-7-O-β-D-葡萄糖苷通过阻断PAF受体而抑制PAF诱导的血小板聚集。

关键词: 高圣草素-7-O-β-D-葡萄糖苷, 血小板活化因子, 血小板活化因子受体, 血小板聚集, 血小板活化因子拮抗剂

Abstract: Homoeriodictyl-7-O-β-D-glycoside, a flavonoid compound isolated from the Chinese medicinal herb, viscum coloratum inhibited platelet aggregation induced by platelet-activating factor(PAF), but it had no inhibitory activity on adenosine diphosphate-induced platelet aggregation. In the present study, we intended to get an insight into the mechanism of its anti-PAF action. Using [³H]PAF receptor binding assay we found that the compound exhibited inhibitory activity. The inhibitory rate was 18.5%, 28.4%, 58.7%, 78% and 78%, respectively, at concentrations of 10^-8, 10^-7, 10^-6, 10^-5 and 10^-4mol·L^-1, There was a visible dose-effect relationship as well as a correlation between different concentrations and their inhibitory rates (γ = 0.985, P<0.05) when the dose was equal to or less than 1×10^-5 mol·L^-1, and its IC50 was 8.0×10^-7 mol·L^-1. The inhibitory rate didn't increase with increasing concentration of the compound when it went beyond 1×10^-5 mol·L^-1 indicating competitive inhibition of binding of [³H]PAF to PAF receptor reached saturation.

Key words: Homoeriodictyol-7-O-β-D-glycoside, Platelet-activating factor antagonist, Platelet-activating factor receptor, Platelet aggregation

Supporting:

管增伟, 王银叶, 杨秀伟, 崔育新. 高圣草素-7-O-β-D-葡萄糖苷抑制血小板活化因子诱导血小板聚集的机理探讨[J]. .

Guan Zengwei, Wang Yinye, Yang Xiuwei, Cui Yuxin . Homoerydictyl-7-O-β-D-glycoside-A Receptor Antagonist of Platelet-activating Factor (PAF)[J]. .

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