Protective role of Ashwagandha leaf extract and its component withanone on scopolamine-induced changes in the brain and brain-derived cells.
Protective role of Ashwagandha leaf extract and its component withanone on scopolamine-induced changes in the brain and brain-derived cells.
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DOI：
10.1371/journal.pone.0027265
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Thakur MK
中科院分区：
文献类型：
--
作者：
Konar A;Shah N;Singh R;Saxena N;Kaul SC;Wadhwa R;Thakur MK
东莨菪碱是一种众所周知的胆碱能拮抗剂，在人类和动物模型中引起健忘症。东莨菪碱引起的啮齿动物遗忘症已被广泛应用于了解记忆障碍的分子、生化、行为变化，以及描述治疗靶点。尽管这与阻断毒蕈碱受体后中枢胆碱能神经元活性的降低有关，但其潜在的分子和细胞机制，特别是对神经可塑性的影响仍然难以捉摸。在本研究中，我们研究了(i)东莨菪碱对体内和体外参与神经元和胶质可塑性的分子的影响，以及（ii） Ashwagandha叶的酒精提取物（i-提取物）对它们的恢复。将氢溴酸东莨菪碱作为药物模型腹腔注射小鼠，通过分子分析确定其对脑功能的影响。结果表明，东莨菪碱对BDNF和GFAP的表达呈剂量依赖性和时间依赖性，且经i-Extract处理后，这种作用明显减弱。与我们在动物模型系统中的观察结果相似，我们发现东莨菪碱对IMR32神经元和C6胶质瘤细胞具有细胞毒性。它与神经元细胞标志物NF-H、MAP2、PSD-95、GAP-43和胶质细胞标志物GFAP的下调以及DNA损伤- γ - h2ax和氧化应激- ROS标志物的上调有关。此外，当细胞用i-Extract或其纯化成分withanone处理时，这些分子表现出恢复。我们的研究表明，除了胆碱能阻断外，东莨菪碱引起的记忆丧失可能与氧化应激和Ashwagandha i-提取物有关，withanone可能作为神经退行性疾病的潜在预防和治疗药物，因此值得进一步的分子分析。
Scopolamine is a well-known cholinergic antagonist that causes amnesia in human and animal models. Scopolamine-induced amnesia in rodent models has been widely used to understand the molecular, biochemical, behavioral changes, and to delineate therapeutic targets of memory impairment. Although this has been linked to the decrease in central cholinergic neuronal activity following the blockade of muscarinic receptors, the underlying molecular and cellular mechanism(s) particularly the effect on neuroplasticity remains elusive. In the present study, we have investigated (i) the effects of scopolamine on the molecules involved in neuronal and glial plasticity both in vivo and in vitro and (ii) their recovery by alcoholic extract of Ashwagandha leaves (i-Extract). As a drug model, scopolamine hydrobromide was administered intraperitoneally to mice and its effect on the brain function was determined by molecular analyses. The results showed that the scopolamine caused downregulation of the expression of BDNF and GFAP in dose and time dependent manner, and these effects were markedly attenuated in response to i-Extract treatment. Similar to our observations in animal model system, we found that the scopolamine induced cytotoxicity in IMR32 neuronal and C6 glioma cells. It was associated with downregulation of neuronal cell markers NF-H, MAP2, PSD-95, GAP-43 and glial cell marker GFAP and with upregulation of DNA damage- γH2AX and oxidative stress- ROS markers. Furthermore, these molecules showed recovery when cells were treated with i-Extract or its purified component, withanone. Our study suggested that besides cholinergic blockade, scopolamine-induced memory loss may be associated with oxidative stress and Ashwagandha i-Extract, and withanone may serve as potential preventive and therapeutic agents for neurodegenerative disorders and hence warrant further molecular analyses.
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DOI：
10.1016/s0169-328x(99)00048-0
发表时间：
1999-04-06
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
French, SJ;Humby, T;Rattray, M
通讯作者：
Rattray, M
影响因子：
2.7
作者：
Komulainen, Pirjo;Pedersen, Maria;Rauramaa, Rainer
通讯作者：
Rauramaa, Rainer
影响因子：
4.7
作者：
Brouillette, Jonathan;Young, Deborah;Quirion, Remi
通讯作者：
Quirion, Remi
影响因子：
0.5
作者：
Drozdov, O. L.;Chorna, V. I.
通讯作者：
Chorna, V. I.
影响因子：
3.4
作者：
KOKAIA, Z;METSIS, M;LINDVALL, O
通讯作者：
LINDVALL, O