title: Antiplatelet aggregation activity of diterpene alkaloids from Spiraea japonica.
abstract: 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 IC(50) values of 30.5+/-2.7, 56.8+/-8.4 and 29.9+/-9.9 microM, 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.
authors.affiliation: Kunning Instiute of Botany, Chinese Academy of Sciences, Heilongtan, Kunming, Yunnan 650204, PR China.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Yue-Mao
authors.initials: YM
authors.lastname: Shen
authors.forename: Xiao-Sheng
authors.initials: XS
authors.lastname: Yang
authors.forename: Guo-Ying
authors.initials: GY
authors.lastname: Zuo
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Shen
authors.forename: Zhi-He
authors.initials: ZH
authors.lastname: Chen
authors.forename: Xiao-Jiang
authors.initials: XJ
authors.lastname: Hao
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects*; D004224:Diterpenes / Q000494:pharmacology*; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology; D046934:Ginkgolides; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007783:Lactones / Q000494:pharmacology; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology; D018517:Plant Roots / Q000737:chemistry; D010972:Platelet Activating Factor / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D031992:Spiraea / Q000737:chemistry*
chemical_list: D000470:Alkaloids; D004224:Diterpenes; D005343:Fibrinolytic Agents; D046934:Ginkgolides; D007202:Indicators and Reagents; D007783:Lactones; D010936:Plant Extracts; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; C045856:ginkgolide B; D001241:Aspirin