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积雪草通过调节大鼠大脑中的胆碱能活性和氧化负荷来缓解 AlCl 诱导的认知障碍、氧化应激和神经退行性变。

Centella asiatica Alleviates AlCl-induced Cognitive Impairment, Oxidative Stress, and Neurodegeneration by Modulating Cholinergic Activity and Oxidative Burden in Rat Brain.

机构信息

Department of Medicinal Chemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, India.

Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology, BHU, Varanasi, 221005, India.

出版信息

Biol Trace Elem Res. 2022 Dec;200(12):5115-5126. doi: 10.1007/s12011-021-03083-5. Epub 2022 Jan 4.

Abstract

Aluminum (Al) is linked to the development of many neurological disorders such as Alzheimer's disease (AD), Parkinson's disease, and autism. Centella asiatica (CA) is a regenerating herb traditionally used to stimulate memory. This study was designed to assess the neuroprotective role of ethanolic extract of CA (CAE) in AlCl-induced neurological conditions in rats. Adult rats were chronically treated with AlCl (100 mg/kg b.w./day) for 60 days to establish the dementia model, and co-administration of CAE was evaluated for its ability to attenuate the toxic effect of AlCl. CAE was given orally at a dose of 150 and 300 mg/kg b.w./day, for 60 days. The behavioral performances of rats were tested through Y-maze and open field tests. Lipid peroxidation, superoxide dismutase, and catalase activity were evaluated to measure oxidative stress; and acetylcholinesterase (AChE) activity was assessed to evaluate cholinergic dysfunction in the rat brain. H&E staining was used to assess structural abnormalities in the cortex and hippocampus. The result showed that AlCl induces cognitive dysfunction (impaired learning and memory, anxiety, diminished locomotor activity), oxidative stress, cholinergic impairment, and histopathological alteration in the rat brain. Co-administration of CAE with AlCl markedly protects the brain from AlCl-induced cognitive dysfunction, oxidative stress, AChE activity, and cytoarchitectural alterations. Furthermore, 15 days CAE treatment after 45 days AlCl administration markedly ameliorates the AlCl-induced neurotoxicity indicating its potential for therapeutic use.

摘要

铝(Al)与许多神经退行性疾病的发展有关,如阿尔茨海默病(AD)、帕金森病和自闭症。积雪草(CA)是一种传统上用于刺激记忆的再生草药。本研究旨在评估积雪草乙醇提取物(CAE)在大鼠 AlCl 诱导的神经疾病中的神经保护作用。成年大鼠连续 60 天每天用 AlCl(100mg/kg b.w.)处理以建立痴呆模型,并评估 CAE 减轻 AlCl 毒性作用的能力。CAE 以 150 和 300mg/kg b.w./天的剂量口服给予 60 天。通过 Y 迷宫和旷场测试测试大鼠的行为表现。评估脂质过氧化、超氧化物歧化酶和过氧化氢酶活性以衡量氧化应激;并评估乙酰胆碱酯酶(AChE)活性以评估大鼠大脑中的胆碱能功能障碍。H&E 染色用于评估皮质和海马体的结构异常。结果表明,AlCl 诱导认知功能障碍(学习和记忆受损、焦虑、运动活动减少)、氧化应激、胆碱能损伤和大鼠大脑的组织病理学改变。CAE 与 AlCl 联合给药可显著保护大脑免受 AlCl 诱导的认知功能障碍、氧化应激、AChE 活性和细胞结构改变的影响。此外,在给予 AlCl 45 天后用 CAE 治疗 15 天可显著改善 AlCl 诱导的神经毒性,表明其具有治疗用途的潜力。

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