Abstract

Overstimulation of glutamate receptors leads to development of excitotoxicity, which is implicated as final destructive pathway in neurodegenerative diseases. Development of alternative therapeutic strategies effective against glutamate-induced excitotoxicity is much in demand. Herbal drug development is emerging as a major research area for the treatment of various debilitating diseases due to multimodal action and least side effects of herbal products. The current study was aimed to investigate neuroprotective potential of butanol extract of Tinospora cordifolia (B-TCE) against glutamate-induced excitotoxicity using primary hippocampal neurons as in vitro and Wistar strain albino rats as in vivo model systems. Molecular and behavioral parameters were studied to elucidate the underlying mechanism of beneficial effects of B-TCE. B-TCE treatment was also effective in prevention of anxiety, cognition, and motor-coordination deficits induced by glutamate. B-TCE pre-treatment protected the hippocampal neurons from glutamate-induced neurodegeneration and impaired plasticity. At molecular level, B-TCE was observed to attenuate overactivation of glutamate receptors. B-TCE promoted upregulation of ERK and AKT pathways of synaptic plasticity and cell survival in the hippocampus region of brain. This study provides first evidence of neuroprotective potential of B-TCE against glutamate-induced excitotoxicity in hippocampus region and suggests that B-TCE may act as a potential candidate for neuroprotective therapeutic approaches. A single compound ‘tinosporicide’ was further isolated from B-TCE, which was found to be effective at 800× lower concentration against glutamate-induced neurodegeneration under in vitro conditions.

中文翻译：

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紫草的丁醇提取物改善了与谷氨酸诱导的兴奋性毒性相关的认知缺陷：使用海马神经元的机制研究。

摘要

谷氨酸受体的过度刺激导致兴奋性毒性的发展，这被认为是神经退行性疾病中的最终破坏途径。迫切需要开发有效对抗谷氨酸引起的兴奋性毒性的替代治疗策略。由于草药产品具有多种作用方式且副作用最小，因此草药药物的开发正成为治疗各种衰弱性疾病的主要研究领域。当前的研究旨在调查心叶丁香的丁醇提取物的神经保护潜力（B-TCE）使用原代海马神经元作为体外和Wistar变种白化病大鼠作为体内模型系统对抗谷氨酸诱导的兴奋性毒性。研究了分子和行为参数，以阐明B-TCE有益作用的潜在机制。B-TCE治疗还可有效预防由谷氨酸引起的焦虑，认知和运动协调障碍。B-TCE预处理可保护海马神经元免受谷氨酸诱导的神经变性和可塑性的损害。在分子水平上，观察到B-TCE减弱了谷氨酸受体的过度活化。B-TCE促进大脑海马区的ERK和AKT通路的突触可塑性和细胞存活的上调。这项研究提供了B-TCE对抗谷氨酸诱导的海马区兴奋性毒性的神经保护潜力的第一个证据，并表明B-TCE可以作为神经保护治疗方法的潜在候选者。从B-TCE进一步分离出单一化合物'tinosporicide'，发现在体外条件下，其浓度低800倍可有效抵抗谷氨酸诱导的神经变性。