Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, #26 Kyungheedae-ro, Dongdeamoon-Gu, Seoul, 130-701, Republic of Korea.
East-West Medical Research Institute, Kyung Hee University Medical Center, Seoul, 130-701, Republic of Korea.
Neurochem Res. 2018 Feb;43(2):351-362. doi: 10.1007/s11064-017-2430-6. Epub 2017 Nov 21.
Eclalbasaponin II derived from Eclipta prostrata L. (Asteraceae) has been reported to have anti-fibrotic, anti-bacterial and autophagic activities, but its effect on cognitive function has not been investigated. We studied the effect of eclalbasaponin II on cholinergic blockade-induced memory impairment in mice using the passive avoidance, Y-maze, and Morris water maze tasks. Eclalbasaponin II (10 or 20 mg/kg, p.o.) significantly ameliorated the cognitive dysfunction induced by scopolamine in the passive avoidance, Y-maze, and the Morris water maze tasks. To identify the mechanism of the memory-ameliorating effect of eclalbasaponin II, acetylcholinesterase (AChE) activity assay, Western blot analysis and electrophysiology were conducted. Eclalbasaponin II inhibited the AChE activity in ex vivo study, and the administration of eclalbasaponin II and its metabolite, echinocystic acid, increased the phosphorylation levels of memory-related signaling molecules, including protein kinase B (Akt) and glycogen synthase kinase-3β (GSK-3β), in the hippocampus. Although eclalbasaponin II did not affect hippocampal long term potentiation (LTP), echinocystic acid significantly enhanced hippocampal LTP formation (30 μM). These results suggest that eclalbasaponin II ameliorates cholinergic blockade-induced cognitive impairment via AChE inhibition, LTP formation and the activation of Akt-GSK-3β signaling, and that eclalbasaponin II may be a useful to treat cognitive impairment derived from cholinergic dysfunction.
从紫菀属植物(Eclipta prostrata L.)中提取的 eclalbasaponin II 已被报道具有抗纤维化、抗菌和自噬活性，但它对认知功能的影响尚未得到研究。我们使用被动回避、Y 迷宫和 Morris 水迷宫任务研究了 eclalbasaponin II 对胆碱能阻断诱导的小鼠记忆障碍的影响。Eclalbasaponin II(10 或 20mg/kg，po)显著改善了 scopolamine 在被动回避、Y 迷宫和 Morris 水迷宫任务中引起的认知功能障碍。为了确定 eclalbasaponin II 改善记忆的作用机制，进行了乙酰胆碱酯酶(AChE)活性测定、Western blot 分析和电生理学研究。Eclalbasaponin II 在离体研究中抑制了 AChE 活性，并且 eclalbasaponin II 和其代谢物，echinocystic acid 的给药增加了记忆相关信号分子的磷酸化水平，包括蛋白激酶 B (Akt) 和糖原合成酶激酶-3β (GSK-3β)，在海马体中。虽然 eclalbasaponin II 不影响海马长时程增强(LTP)，但 echinocystic acid 显著增强了海马 LTP 的形成(30μM)。这些结果表明，Eclalbasaponin II 通过 AChE 抑制、LTP 形成和 Akt-GSK-3β 信号的激活改善了胆碱能阻断诱导的认知障碍，并且 eclalbasaponin II 可能是治疗胆碱能功能障碍引起的认知障碍的有用药物。
