Lima Josélia A, Costa Rodrigo Saar, Epifânio Rosangela A, Castro Newton G, Rocha Mônica S, Pinto Angelo C
Departamento de Química Orgânica, Instituto de Química, Universidade Federal do Rio de Janeiro, 21941-909 Rio de Janeiro, RJ, Brazil.
Pharmacol Biochem Behav. 2009 May;92(3):508-13. doi: 10.1016/j.pbb.2009.01.024. Epub 2009 Feb 5.
This study evaluated the cholinesterase inhibitory activity of an alkaloid-rich fraction of stembark from Geissospermum vellosii (PP), and its effect on memory tests in mice. PP inhibited rat brain and electric eel acetylcholinesterase, as well as horse serum butyrylcholinesterase in a concentration-dependent manner with mean IC(50) values of 39.3 microg/mL, 2.9 microg/mL, and 1.6 microg/mL, respectively. The main alkaloid with anticholinesterase activity in PP was isolated and identified as geissospermine. PP significantly reduced scopolamine-induced amnesia in the passive avoidance and Morris water maze tests, at 30 mg/kg i.p. (given 45 min before the test sessions). At the highest effective dose (60 mg/kg), administration of PP did not result in noticeable peripheral or central cholinergic side effects. Only after administration of 200 mg/kg, mice showed convulsions affecting the whole body followed by death. These results show that compounds present in G. vellosii stembark have anticholinesterase activity, and that they can revert cognitive deficits in a model of cholinergic hypofunction.
本研究评估了绒毛盖萼木（Geissospermum vellosii，PP）茎皮中富含生物碱的部分的胆碱酯酶抑制活性及其对小鼠记忆测试的影响。PP以浓度依赖性方式抑制大鼠脑和电鳗乙酰胆碱酯酶以及马血清丁酰胆碱酯酶，其平均IC（50）值分别为39.3微克/毫升、2.9微克/毫升和1.6微克/毫升。PP中具有抗胆碱酯酶活性的主要生物碱被分离并鉴定为盖萼木胺。在被动回避和莫里斯水迷宫测试中，PP（腹腔注射30毫克/千克，在测试前45分钟给药）显著减轻了东莨菪碱诱导的失忆。在最高有效剂量（60毫克/千克）下，给予PP未导致明显的外周或中枢胆碱能副作用。仅在给予200毫克/千克后，小鼠出现全身惊厥，随后死亡。这些结果表明，绒毛盖萼木茎皮中的化合物具有抗胆碱酯酶活性，并且它们可以在胆碱能功能减退模型中恢复认知缺陷。
