Myint Su Lwin Lwin, Rodsiri Ratchanee, Benya-Aphikul Hattaya, Rojanaratha Tissana, Ritthidej Garnpimol, Islamie Ridho
Department of Pharmacology and Physiology Faculty of Pharmaceutical Sciences Chulalongkorn University, Bangkok 10330, Thailand.
Preclinical Toxicity and Efficacy Assessment of Medicines and Chemicals Research Unit Chulalongkorn University, Bangkok 10330, Thailand.
Adv Pharmacol Pharm Sci. 2024 Sep 9;2024:9941034. doi: 10.1155/2024/9941034. eCollection 2024.
Asiatic acid (AA) has previously shown its neuroprotective effects, but low oral bioavailability limits its penetration into the brain. This study aimed to investigate the effect of intranasal AA administration in mice with memory dysfunction induced by scopolamine. Mice received either intranasal AA (INAA), oral AA (POAA3 or POAA30), or donepezil, followed by scopolamine for 10 days. Morris water maze (MWM) was performed on days 0-5, 30 min after treatment. Locomotor activity was conducted on day 6 followed by brain collection. In MWM, INAA treatment had significantly reduced escape latency on days 2-4, while POAA3 decreased escape latency on day 3 and POAA30 and donepezil decreased escape latency on day 4. INAA inhibited acetylcholinesterase activity, increased catalase protein expression, and decreased malondialdehyde levels in the brain tissue. Therefore, intranasal administration of AA produced a rapid onset in the protection of learning and memory deficits induced by scopolamine through acetylcholinesterase inhibition and antioxidant effect.
齐墩果酸(AA)先前已显示出其神经保护作用,但口服生物利用度低限制了其进入大脑。本研究旨在探讨鼻内给予AA对东莨菪碱诱导的记忆功能障碍小鼠的影响。小鼠接受鼻内AA(INAA)、口服AA(POAA3或POAA30)或多奈哌齐治疗,随后给予东莨菪碱10天。在治疗后30分钟的第0 - 5天进行莫里斯水迷宫(MWM)实验。在第6天进行运动活动测试,随后采集大脑。在MWM实验中,INAA治疗在第2 - 4天显著缩短了逃避潜伏期,而POAA3在第3天缩短了逃避潜伏期,POAA30和多奈哌齐在第4天缩短了逃避潜伏期。INAA抑制了脑组织中的乙酰胆碱酯酶活性,增加了过氧化氢酶蛋白表达,并降低了丙二醛水平。因此,鼻内给予AA通过抑制乙酰胆碱酯酶和抗氧化作用,对东莨菪碱诱导的学习和记忆缺陷产生了快速起效的保护作用。