Xian Yan-Fang, Ip Siu-Po, Mao Qing-Qiu, Su Zi-Ren, Chen Jian-Nan, Lai Xiao-Ping, Lin Zhi-Xiu
School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.
School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.
Eur J Pharmacol. 2015 Aug 5;760:88-95. doi: 10.1016/j.ejphar.2015.04.013. Epub 2015 Apr 23.
Honokiol, a lignan isolated from the bark of Magnolia officinalis, has been reported to ameliorate the learning and memory impairments in senesed (SAMP8) mice. However, whether honokiol could improve scopolamine (SCOP)-induced learning and memory deficits in mice is still unknown. In this study, we aimed to investigate whether honokiol could reverse the SCOP-induced learning and memory impairments in mice and to elucidate its underlying mechanisms of action. Mice were given daily intraperitoneal injection of honokiol (10 and 20mg/kg) for 21 consecutive days. The results showed that honokiol significantly improved spatial learning and memory function (as assessed by the Morris water maze test) in the SCOP-treated mice. In addition, treatment with honokiol significantly decreased the protein and mRNA levels of interleukin (IL)-1β and the activity of acetylcholinesterase (AChE), while significantly increased the protein and mRNA levels of IL-10, and the level of acetylcholine (Ach) in the brain of the SCOP-treated mice. Moreover, honokiol also significantly suppressed the production of prostaglandin E 2 (PGE2) and mRNA expression of cyclooxygenase-2 (COX-2) in the brain of the SCOP-treated mice. Mechanistic investigations revealed that honokiol could markedly reverse the amount of phosphorylated Akt and extracellular regulated kinases 1/2 (ERK1/2) changes in the brain of the SCOP-treated mice. These results amply demonstrated that honokiol could improve learning and memory impairments induced by SCOP in mice, and the protective action may be mediated, at least in part, by inhibition of AChE activity, and amelioration of the neuroinflammatory processes in the SCOP-treated mice.
厚朴酚是从厚朴树皮中分离出的一种木脂素，据报道它可改善衰老（SAMP8）小鼠的学习和记忆障碍。然而，厚朴酚是否能改善东莨菪碱（SCOP）诱导的小鼠学习和记忆缺陷仍不清楚。在本研究中，我们旨在研究厚朴酚是否能逆转SCOP诱导的小鼠学习和记忆障碍，并阐明其潜在的作用机制。小鼠连续21天每天腹腔注射厚朴酚（10和20mg/kg）。结果表明，厚朴酚显著改善了SCOP处理小鼠的空间学习和记忆功能（通过莫里斯水迷宫试验评估）。此外，厚朴酚处理显著降低了白细胞介素（IL）-1β的蛋白质和mRNA水平以及乙酰胆碱酯酶（AChE）的活性，同时显著增加了SCOP处理小鼠大脑中IL-10的蛋白质和mRNA水平以及乙酰胆碱（Ach）的水平。此外，厚朴酚还显著抑制了SCOP处理小鼠大脑中前列腺素E2（PGE2）的产生和环氧合酶-2（COX-2）的mRNA表达。机制研究表明，厚朴酚可显著逆转SCOP处理小鼠大脑中磷酸化Akt和细胞外调节激酶1/2（ERK1/2）的变化量。这些结果充分证明，厚朴酚可以改善SCOP诱导的小鼠学习和记忆障碍，其保护作用可能至少部分是通过抑制AChE活性以及改善SCOP处理小鼠的神经炎症过程来介导的。
