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山茱萸苷改善东莨菪碱诱导的AD小鼠的认知障碍:神经递质和氧化应激的作用

Cornuside ameliorates cognitive impairments in scopolamine induced AD mice: Involvement of neurotransmitter and oxidative stress.

作者信息

Wang Ze-Xing, Lian Wen-Wen, He Jun, He Xiao-Li, Wang Yu-Ming, Pan Chen-Hao, Li Mei, Zhang Wei-Ku, Liu Lian-Qi, Xu Jie-Kun

机构信息

School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 100029, People's Republic of China; Institute of Clinical Medical Sciences & Department of Pharmacy, China-Japan Friendship Hospital, Beijing, 100029, People's Republic of China.

Institute of Clinical Medical Sciences & Department of Pharmacy, China-Japan Friendship Hospital, Beijing, 100029, People's Republic of China.

出版信息

J Ethnopharmacol. 2022 Jul 15;293:115252. doi: 10.1016/j.jep.2022.115252. Epub 2022 Apr 9.

DOI:10.1016/j.jep.2022.115252
PMID:35405255
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Cornus officinalis Sieb. et Zucc., traditional Chinese medicine, has been widely used in the treatment of dementia. Cornel iridoid glycosides of Cornus officinalis is therapeutic to Alzheimer's disease (AD), while its pharmacodynamic material basis is not clear. Cornuside, an iridoid glycoside extracted from of Cornus officinalis Sieb. et Zucc, might be a potential anti-AD candidate.

AIM OF THE STUDY

Cornuside was evaluated for its effect on scopolamine induced AD mice, and its action mechanisms were explored.

MATERIALS AND METHODS

ICR mice were administered with 1 mg/kg scopolamine intraperitoneally to induce amnesia. The therapeutic effect of cornuside of cognitive function was evaluated via series of behavioral tests, including Morris water maze test, step-through test and step-down test. In addition, specific enzyme reaction tests were used to detect the content of acetylcholine (ACh) and malondialdehyde (MDA), as well as the activities of acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), choline acetyltransferase (ChAT), superoxide dismutase (SOD), catalase (CAT), monoamine oxidase (MAO) in the brain. The levels of monoamine neurotransmitters were detected by high performance liquid chromatography-electrochemical detection (HPLC-ECD).

RESULTS

Cornuside ameliorated the spatial memory impairment in Morris water maze test and cognitive disruption in step-through and step-down test. Furthermore, cornuside improved the level of ACh by reducing the activities of AChE and BuChE, and increasing the activity of ChAT in hippocampus. Cornuside also increased the levels of monoamine neurotransmitters by inhibiting MAO activity in hippocampus and cortex. In addition, cornuside attenuated MDA by enhancing the activities of SOD and CAT in hippocampus and cortex.

CONCLUSION

Cornuside improved cognitive dysfunction induced by scopolamine in behavioral tests. The mechanisms of cornuside were further investigated from the aspects of neurotransmitters and oxidative stress. Cornuside could inhibit oxidative stress and neurotransmitter hydrolases, increase ACh and monoamine neurotransmitters, which finally contributed to its therapeutic effect on scopolamine induced amnesia.

摘要

民族药理学相关性

山茱萸,一种传统中药,已被广泛用于治疗痴呆症。山茱萸中的山茱萸环烯醚萜苷对阿尔茨海默病(AD)具有治疗作用,但其药效物质基础尚不清楚。从山茱萸中提取的环烯醚萜苷山茱萸苷可能是一种潜在的抗AD候选药物。

研究目的

评估山茱萸苷对东莨菪碱诱导的AD小鼠的作用,并探讨其作用机制。

材料与方法

将ICR小鼠腹腔注射1mg/kg东莨菪碱以诱导失忆。通过一系列行为测试,包括莫里斯水迷宫试验、穿梭试验和跳台试验,评估山茱萸苷对认知功能的治疗效果。此外,采用特定酶反应试验检测大脑中乙酰胆碱(ACh)和丙二醛(MDA)的含量,以及乙酰胆碱酯酶(AChE)、丁酰胆碱酯酶(BuChE)、胆碱乙酰转移酶(ChAT)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、单胺氧化酶(MAO)的活性。通过高效液相色谱-电化学检测(HPLC-ECD)检测单胺类神经递质的水平。

结果

山茱萸苷改善了莫里斯水迷宫试验中的空间记忆障碍以及穿梭试验和跳台试验中的认知障碍。此外,山茱萸苷通过降低海马体中AChE和BuChE的活性以及增加ChAT的活性来提高ACh水平。山茱萸苷还通过抑制海马体和皮层中MAO的活性来增加单胺类神经递质的水平。此外,山茱萸苷通过增强海马体和皮层中SOD和CAT的活性来减轻MDA。

结论

在行为测试中,山茱萸苷改善了东莨菪碱诱导的认知功能障碍。从神经递质和氧化应激方面对山茱萸苷的作用机制进行了进一步研究。山茱萸苷可以抑制氧化应激和神经递质水解酶,增加ACh和单胺类神经递质,最终促成其对东莨菪碱诱导失忆的治疗作用。

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