去氧野百合堿通过恢复胆碱能功能改善东莨菪碱诱导的小鼠认知功能障碍。
Ameliorative effect of deoxyvasicine on scopolamine-induced cognitive dysfunction by restoration of cholinergic function in mice.
机构信息
Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine; The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine, 1200 Cailun Rood, Shanghai 201203, China; Pingxiang Health Vocational College, Pingxiang 337000, China.
Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine; The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine, 1200 Cailun Rood, Shanghai 201203, China.
出版信息
Phytomedicine. 2019 Oct;63:153007. doi: 10.1016/j.phymed.2019.153007. Epub 2019 Jul 2.
BACKGROUND
Aerial parts of Peganum harmala Linn is used as a traditional medical herb for treatment of amnesia in Uighur medicine in China. Deoxyvasicine (DVAS) is one of the chief active ingredients in P. harmala, it possesses strong acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities in vitro, but the therapeutic effect and mechanisms on amnesia in vivo are unclear.
PURPOSE
The objective of this study was to investigate the improvement effect of DVAS from P. harmala in learning and memory deficits of scopolamine-induced mice and elucidate the underlying mechanisms involved.
METHODS
Mice were pretreated with DVAS (5, 15 and 45 mg/kg) and huperzine-A (0.2 mg/kg) by gavage for 7 days, and subsequently were daily intraperitoneally injected with scopolamine (1 mg/kg) to induce learning and memory deficits and behavioral performance was assessed by Morris water maze. To further evaluate the potential mechanisms of DVAS in improving learning and memory capabilities, pathological change, levels of various biochemical markers and protein expressions related to cholinergic system, oxidative stress, and neuroinflammation were examined.
RESULTS
The results showed that DVAS could alleviate learning and memory deficits in scopolamine-treated mice. DVAS could regulate cholinergic function by inhibiting AChE and activating choline acetyltransferase (ChAT) activities and protein expressions. DVAS could induce brain-derived neurotrophic factor and protect hippocampal pyramidal cells against neuronal damage. DVAS also enhanced antioxidant defense via increasing the antioxidant enzyme level and activity of glutathione peroxidase, and anti-inflammatory function through suppressing tumor necrosis factor-α. Additionally, DVAS could regulate the neurotransmitters by elevating acetylcholine, 5-hydroxytryptamine, γ-aminobutyric acid and reducing 5-hydroxyindole-3-acetic acid and glutamic acid.
CONCLUSION
Results illustrated that DVAS may be a promising candidate compound against amnesia via restoration of cholinergic function, regulating neurotransmitters, attenuating neuroinflammation and oxidative stress.
背景
骆驼蓬的地上部分在中国维吾尔医学中被用作治疗健忘症的传统草药。脱氧育亨宾碱（DVAS）是骆驼蓬的主要活性成分之一，它在体外具有很强的乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BChE）抑制活性，但在体内对健忘症的治疗效果和机制尚不清楚。
目的
本研究旨在探讨 DVAS 对东莨菪碱诱导的小鼠学习记忆障碍的改善作用，并阐明其潜在的作用机制。
方法
小鼠用 DVAS（5、15 和 45mg/kg）和石杉碱甲（0.2mg/kg）灌胃预处理 7 天，然后每天腹腔注射东莨菪碱（1mg/kg）诱导学习记忆障碍，并通过 Morris 水迷宫评估行为表现。为了进一步评估 DVAS 改善学习记忆能力的潜在机制，检测了与胆碱能系统、氧化应激和神经炎症相关的病理变化、各种生化标志物水平和蛋白表达。
结果
结果表明，DVAS 可缓解东莨菪碱处理小鼠的学习记忆障碍。DVAS 可通过抑制 AChE 和激活胆碱乙酰转移酶（ChAT）活性和蛋白表达来调节胆碱能功能。DVAS 可诱导脑源性神经营养因子并保护海马锥体神经元免受神经元损伤。DVAS 还通过增加抗氧化酶水平和谷胱甘肽过氧化物酶活性来增强抗氧化防御功能，并通过抑制肿瘤坏死因子-α来发挥抗炎作用。此外，DVAS 可通过提高乙酰胆碱、5-羟色胺、γ-氨基丁酸水平和降低 5-羟吲哚-3-乙酸和谷氨酸来调节神经递质。
结论
结果表明，DVAS 可能通过恢复胆碱能功能、调节神经递质、减轻神经炎症和氧化应激，成为治疗健忘症的有前途的候选化合物。
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