Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
Department of Applied Biological Science, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
Prog Neuropsychopharmacol Biol Psychiatry. 2016 Nov 3;71:155-61. doi: 10.1016/j.pnpbp.2016.08.002. Epub 2016 Aug 2.
Neoechinulin A is an isoprenyl indole alkaloid that exhibits scavenging, neurotrophic factor-like, and anti-apoptotic activities. However, the effectiveness of neoechinulin A in animal models of disease has not yet been explored. In the present study, we investigated the effects of neoechinulin A on memory impairment in lipopolysaccharide (LPS)-treated mice and its antidepressant-like effects in mice. In the Y-maze test, the intracerebroventicular (i.c.v.) administration of LPS (10μg/mouse) significantly decreased spontaneous alternation behavior, which was prevented by the prior administration of neoechinulin A (300ng/mouse, i.c.v.). None of the treatments altered the locomotor activity of mice. Moreover, the administration of neoechinulin A decreased the immobility time in the forced-swim test or tail suspension test, which was prevented by the prior administration of WAY100635 (an antagonist of 5-HT1A receptors) and parachlorophenylalanine (an inhibitor of tryptophan hydroxylase). These results suggest that neoechinulin A improves memory functions in LPS-treated mice, and also exerts antidepressant-like effects through changes in the 5-HT system.
新海南素 A 是一种异戊烯基吲哚生物碱，具有清除自由基、神经营养因子样和抗细胞凋亡活性。然而，新海南素 A 在疾病动物模型中的有效性尚未得到探索。在本研究中，我们研究了新海南素 A 对脂多糖（LPS）处理的小鼠记忆障碍的影响及其在小鼠中的抗抑郁样作用。在 Y 迷宫测试中，脑室内（i.c.v.）给予 LPS（10μg/只）显著降低自发交替行为，而新海南素 A（300ng/只，i.c.v.）预先给予可预防这种行为。这些处理均未改变小鼠的运动活性。此外，新海南素 A 给药可减少强迫游泳试验或悬尾试验中的不动时间，而 5-HT1A 受体拮抗剂 WAY100635 和色氨酸羟化酶抑制剂对氯苯丙氨酸的预先给予可预防这种作用。这些结果表明，新海南素 A 改善 LPS 处理的小鼠的记忆功能，并通过 5-HT 系统的变化发挥抗抑郁样作用。
