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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Systemic administration of defined extracts from Withania somnifera (Indian Ginseng) and Shilajit differentially affects cholinergic but not glutamatergic and GABAergic markers in rat brain.
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Systemic administration of defined extracts from Withania somnifera (Indian Ginseng) and Shilajit differentially affects cholinergic but not glutamatergic and GABAergic markers in rat brain.

机译：全身性服用Withania somnifera（印度人参）和Shilajit的特定提取物对大鼠脑内胆碱能标记和谷氨酸能标记和GABA能标记有不同的影响。

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摘要

Although some promising results have been achieved by acetylcholinesterase inhibitors, an effective therapeutic intervention in Alzheimer's disease still remains an important goal. Sitoindosides VII-X, and withaferin-A, isolated from aqueous methanol extract from the roots of cultivated varieties of Withania somnifera (known as Indian Ginseng), as well as Shilajit, a pale-brown to blackish brown exudation from steep rocks of the Himalaya mountain, are used in Indian medicine to attenuate cerebral functional deficits, including amnesia, in geriatric patients. The present investigation was conducted to assess whether the memory-enhancing effects of plant extracts from Withania somnifera and Shilajit are owing to neurochemical alterations of specific transmitter systems. Therefore, histochemistry to analyse acetylcholinesterase activity as well as receptor autoradiography to detect cholinergic, glutamatergic and GABAergic receptor subtypes were performed in brain slices from adult male Wistar rats, injected intraperitoneally daily with an equimolar mixture of sitoindosides VII-X and withaferin-A (prepared from Withania somnifera) or with Shilajit, at doses of 40 mg/kg of body weight for 7 days. Administration of Shilajit led to reduced acetylcholinesterase staining, restricted to the basal forebrain nuclei including medial septum and the vertical limb of the diagonal band. Systemic application of the defined extract from Withania somnifera, however, led to differential effects on AChE activity in basal forebrain nuclei: slightly enhanced AChE activity was found in the lateral septum and globus pallidus, whereas in the vertical diagonal band AChE activity was reduced following treatment with sitoindosides VII-X and withaferin-A. These changes were accompanied by enhanced M1-muscarinic cholinergic receptor binding in lateral and medial septum as well as in frontal cortices, whereas the M2-muscarinic receptor binding sites were increased in a number of cortical regions including cingulate, frontal, piriform, parietal and retrosplenial cortex. Treatment with Shilajit or the defined extract from Withania somnifera affected neither GABAA and benzodiazepine receptor binding nor NMDA and AMPA glutamate receptor subtypes in any of the cortical or subcortical regions studied. The data suggest that Shilajit and the defined extract from Withania somnifera affect preferentially events in the cortical and basal forebrain cholinergic signal transduction cascade. The drug-induced increase in cortical muscarinic acetylcholine receptor capacity might partly explain the cognition-enhancing and memory-improving effects of extracts from Withania somnifera observed in animals and humans.
机译：尽管乙酰胆碱酯酶抑制剂已经取得了一些有希望的结果，但是对阿尔茨海默氏病的有效治疗干预仍然是重要的目标。 Sitoindosides VII-X和withaferin-A，是从取自Withania somnifera（被称为印度人参）的栽培品种和喜马拉雅山陡峭岩石上的浅棕色至黑褐色渗出物的Shilajit的甲醇提取液中分离的山，在印度医学中用于减轻老年患者的脑功能障碍，包括健忘症。进行本研究以评估来自Withania somnifera和Shilajit的植物提取物的记忆增强作用是否归因于特定递质系统的神经化学改变。因此，在成年雄性Wistar大鼠的脑切片中进行了组织化学分析乙酰胆碱酯酶活性以及受体放射自显影，以检测胆碱能，谷氨酸能和GABA能受体亚型，每天腹膜内注射等摩尔的西多苷（sitoindosides）VII-X和withferin-A（制备）。 （来自Withania somnifera）或Shilajit，剂量为40 mg / kg体重，持续7天。施用Shilajit导致乙酰胆碱酯酶染色减少，仅限于基底前脑核，包括中隔和对角带的垂直肢。然而，全身性使用Withania somnifera的确定提取物会导致对基础前脑核中AChE活性的不同影响：在外侧中隔和苍白球中发现AChE活性略有增强，而在处理后垂直对角带中AChE活性降低含西妥糖苷VII-X和withaferin-A。这些变化伴随着外侧和内侧中隔以及额叶皮层中M1毒蕈碱胆碱能受体的结合增强，而M2毒蕈碱受体的结合位点在许多皮质区域（包括扣带，额叶，梨状，顶叶和脾后区）增加皮层。用Shilajit或从Withania somnifera提取的特定提取物进行处理，在所研究的任何皮层或皮层下区域均不影响GABAA和苯并二氮杂receptor受体结合，也不影响NMDA和AMPA谷氨酸受体亚型。数据表明，Shilajit及其从Withania somnifera中提取的提取物优先影响皮质和基底前脑胆碱能信号转导级联反应。药物诱导的皮质毒蕈碱型乙酰胆碱受体能力的增加可能部分解释了在动物和人体内观察到的With Withania somnifera提取物的认知增强和记忆改善作用。

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