Antiplatelet aggregation activity of diterpene alkaloids from Spiraea japonica

作者：Li L; Shen YM; Yang XS; Zuo GY; Shen ZQ; Chen ZH; Hao XJ^*

来源：European Journal of Pharmacology, 2002, 449(1-2): 23-28.

DOI：10.1016/s0014-2999(02)01627-8

• atisine-type diterpene alkaloid
• platelet aggregation
• arachidonic acid
• adenosine-5 '
• -diphosphate
• PAF (platelet-activating factor)
• structure-activity relationship

Six diterpene alkaloids with an atisine-type C-20-skeleton isolated from the Chinese herbal medicines Spiraea japonica var. acuta and S. japonica var. ovalifolia, as well as eight derivatives of spiramine C and spiradine F were evaluated for the ability to inhibit aggregation of rabbit platelets induced by arachidonic acid, ADP, and platelet-activating factor (PAF) in vitro. The results showed that 12 of the 14 atisine-type diterpene alkaloids significantly inhibited PAF-induced platelet aggregation in a concentration-dependent manner, but had no effect on ADP- or arachidonic acid-induced aggregation, exhibiting a selective inhibition. It is the first report that C-20-diterpene alkaloids inhibit PAF-induced platelet aggregation. However, spiramine C1 concentration-dependently inhibited platelet aggregation induced by PAF, ADP and arachidonic acid with IC50 values of 30.5 +/- 2.7, 56.8 +/- 8.4 and 29.9 +/- 9.9 muM, respectively, suggesting a non-selective antiplatelet aggregation action. The inhibitory effect of spiramine C1 on arachidonic acid was as potent as that of aspirin. Primary studies of the structure-activity relationships for inhibition of PAF-induced aggregation showed that the oxygen substitution at the C-15 position and the presence of an oxazolidine ring in spiramine alkaloids were essential to their antiplatelet aggregation effects. These results suggest that the atisine-type alkaloids isolated from S. japonica are a class of novel antiplatelet aggregation agents.

• 出版日期2002-8-2
• 单位贵州省中国科学院天然产物化学重点实验室; 中国科学院昆明植物研究所; 昆明医科大学