Kim Hyun-Bum, Lee Seok, Hwang Eun-Sang, Maeng Sungho, Park Ji-Ho
Graduate School of East-West Medical Science, Kyung Hee University, Deogyeong-daero, Giheung-gu, Yongin-si, Gyeonggi-do, 446-701, Republic of Korea.
Graduate School of East-West Medical Science, Kyung Hee University, Deogyeong-daero, Giheung-gu, Yongin-si, Gyeonggi-do, 446-701, Republic of Korea.
Biochem Biophys Res Commun. 2017 Oct 21;492(3):493-499. doi: 10.1016/j.bbrc.2017.08.068. Epub 2017 Aug 19.
Due to the improvement of medical level, life expectancy increased. But the increased incidence of cognitive disorders is an emerging social problem. Current drugs for dementia treatment can only delay the progress rather than cure. p-Coumaric acid is a phenylpropanoic acid derived from aromatic amino acids and known as a precursor for flavonoids such as resveratrol and naringenin. It was shown to reduce oxidative stress, inhibit genotoxicity and exert neuroprotection. Based on these findings, we evaluated whether p-coumaric acid can protect scopolamine induced learning and memory impairment by measuring LTP in organotypic hippocampal slice and cognitive behaviors in rats. p-Coumaric acid dose-dependently increased the total activity of fEPSP after high frequency stimulation and attenuated scopolamine-induced blockade of fEPSP in the hippocampal CA1 area. In addition, while scopolamine shortened the step-through latency in the passive avoidance test and prolonged the latency as well as reduced the latency in the target quadrant in the Morris water maze test, co-treatment of p-coumaric acid improved avoidance memory and long-term retention of spatial memory in behavioral tests. Since p-coumaric acid improved electrophysiological and cognitive functional deterioration by scopolamine, it may have regulatory effects on central cholinergic synapses and is expected to improve cognitive problems caused by abnormality of the cholinergic nervous system.
由于医疗水平的提高,预期寿命增加。但认知障碍发病率的上升是一个新出现的社会问题。目前用于治疗痴呆症的药物只能延缓病情发展而无法治愈。对香豆酸是一种源自芳香族氨基酸的苯丙酸,是白藜芦醇和柚皮素等类黄酮的前体。研究表明它能减轻氧化应激、抑制基因毒性并发挥神经保护作用。基于这些发现,我们通过测量器官型海马脑片的长时程增强(LTP)和大鼠的认知行为,评估了对香豆酸是否能保护东莨菪碱诱导的学习和记忆损伤。对香豆酸在高频刺激后剂量依赖性地增加了场兴奋性突触后电位(fEPSP)的总活性,并减轻了东莨菪碱诱导的海马CA1区fEPSP阻断。此外,虽然东莨菪碱缩短了被动回避试验中的穿通潜伏期,延长了莫里斯水迷宫试验中的潜伏期,并缩短了目标象限的潜伏期,但对香豆酸的联合治疗在行为测试中改善了回避记忆和空间记忆的长期保持。由于对香豆酸改善了东莨菪碱引起的电生理和认知功能恶化,它可能对中枢胆碱能突触有调节作用,有望改善由胆碱能神经系统异常引起的认知问题。