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牛膝草(Achyranthes aspera L.)基于计算机辅助指导的新型益智潜力的药理学验证

Pharmacological validation of in-silico guided novel nootropic potential of Achyranthes aspera L.

作者信息

Gawande Dinesh Yugraj, Goel Rajesh Kumar

机构信息

Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, Punjab, India.

Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, Punjab, India.

出版信息

J Ethnopharmacol. 2015 Dec 4;175:324-34. doi: 10.1016/j.jep.2015.09.025. Epub 2015 Sep 25.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Achyranthes aspera (A. aspera) has been used as a brain tonic in folk medicine. Although, ethnic use of medicinal plant has been basis for drug discovery from medicinal plants, but the available in-silico tools can be useful to find novel pharmacological uses of medicinal plants beyond their ethnic use.

AIM OF THE STUDY

To validate in-silico prediction for novel nootropic effect of A. aspera by employing battery of tests in mice.

MATERIAL AND METHODS

Phytoconstituents of A. aspera reported in Dictionary of Natural Product were subjected to in-silico prediction using PASS and Pharmaexpert. The nootropic activity predicted for A. aspera was assessed using radial arm maze, passive shock avoidance and novel object recognition tests in mice. After behavioral evaluation animals were decapitated and their brains were collected and stored for estimation of glutamate levels and acetylcholinesterase activity.

RESULTS

In-silico activity spectrum for majority of A. aspera phytoconstituents exhibited excellent prediction score for nootropic activity of this plant. A. aspera extract treatment significantly improved the learning and memory as evident by decreased working memory errors, reference memory errors and latency time in radial arm maze, step through latency in passive shock avoidance and increased recognition index in novel object recognition were observed, moreover significantly enhanced glutamate levels and reduced acetylcholinesterase activity in hippocampus and cortex were observed as compared to the saline treated group.

CONCLUSION

In-silico and in-vivo results suggest that A. aspera plant may improve the learning and memory by modulating the brain glutamatergic and cholinergic neurotransmission.

摘要

民族药理学相关性

土牛膝在民间医学中被用作补脑剂。虽然民族对药用植物的使用一直是从药用植物中发现药物的基础,但现有的计算机模拟工具可有助于发现药用植物超出其民族用途的新药理用途。

研究目的

通过在小鼠中进行一系列试验,验证土牛膝新的益智作用的计算机模拟预测。

材料与方法

使用PASS和Pharmaexpert对《天然产物词典》中报道的土牛膝植物成分进行计算机模拟预测。使用小鼠的放射状臂迷宫、被动回避电击和新物体识别试验评估预测的土牛膝益智活性。行为评估后,将动物断头并收集其大脑,储存用于评估谷氨酸水平和乙酰胆碱酯酶活性。

结果

大多数土牛膝植物成分的计算机模拟活性谱对该植物的益智活性显示出优异的预测分数。土牛膝提取物处理显著改善了学习和记忆,这在放射状臂迷宫中工作记忆错误、参考记忆错误和潜伏期时间减少、被动回避电击的步过潜伏期以及新物体识别中的识别指数增加中得到明显体现,此外,与生理盐水处理组相比,观察到海马体和皮质中的谷氨酸水平显著提高,乙酰胆碱酯酶活性降低。

结论

计算机模拟和体内实验结果表明,土牛膝可能通过调节大脑谷氨酸能和胆碱能神经传递来改善学习和记忆。

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