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钩吻生药再制剂改善东莨菪碱诱导痴呆模型小鼠的记忆和认知障碍。

Reconstituted mother tinctures of Gelsemium sempervirens L. improve memory and cognitive impairment in mice scopolamine-induced dementia model.

机构信息

Dr. B. C. Roy College of Pharmacy and Allied Health Sciences, Division of Pharmacognosy and Phytochemistry, Bidhan Nagar, Durgapur 713206, India.

Dr. B. C. Roy College of Pharmacy and Allied Health Sciences, Division of Pharmacognosy and Phytochemistry, Bidhan Nagar, Durgapur 713206, India.

出版信息

J Ethnopharmacol. 2015 Jan 15;159:274-84. doi: 10.1016/j.jep.2014.09.008. Epub 2014 Nov 21.

DOI:10.1016/j.jep.2014.09.008
PMID:25459447
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Gelsemium sempervirens (L.) J.St.-Hil is a herb used for the treatment of various neuroses in both homeopathic and Ayurvedic systems. The present study examines whether Gelsemium reconstituted tincture can protect against scopolamine induced cognitive discrepancies in amnesic mouse model. In order to investigate the protective mechanism of Gelsemium against dementia, in vitro acetyl cholinesterase and β-secretase enzyme inhibition and estimation of glutathione level in mouse brain were carried out.

MATERIALS AND METHODS

The inhibition study on acetyl cholinesterase and β-secretase enzyme was conducted on brain homogenate supernatant spectrophotometrically using specific substrate. Cognitive enhancement activity was assessed by elevated plus maze and passive avoidance study in scopolamine induced dementia mouse model. Glutathione, an anti-oxidant, was measured spectrophotometrically from scopolamine induced amnesic mice brain supernatant using 5,5'-dithiobis 2-nitrobenzoic acid in the presence and absence of Gelsemium tincture.

RESULTS

Significant inhibition was found with Gelsemium on AChE and β-secretase enzyme with an IC50 of 9.25 and 16.25 µg/ml, respectively, followed by increasing glutathione levels in comparison to the untreated dementia group. The effect of Gelsemium of scopolamine-induced cognitive deficits was determined by measuring the behavioral parameters and the antioxidant status of the brain after scopolamine (1mg/kg i.p.) injected amnesic mice. Gelsemium significantly demonstrated in vivo anti-dementia activity (60% protection) and increased exploratory behavior.

CONCLUSION

Our investigations indicated that alkaloid, iridoids and coumarin enriched reconstituted Gelsemium tincture extract displays promising cognitive enhancement in adult mice after short-term oral treatment. Hence, Gelsemium can be a promising anti-dementia agent, mediating the protection against amnesia, attention disorders and learning dysfunctions through dual inhibition of both acetyl cholinesterases (no false positive effect was shown), β-secretase and antioxidant activity.

摘要

民族药理学相关性

钩吻(L.)J.St.-Hil 是一种草药,用于顺势疗法和阿育吠陀系统治疗各种神经症。本研究探讨了钩吻再体制剂酊剂是否可以预防东莨菪碱引起的健忘症小鼠模型中的认知差异。为了研究钩吻对痴呆症的保护机制,进行了体外乙酰胆碱酯酶和β-分泌酶抑制以及小鼠大脑谷胱甘肽水平的测定。

材料和方法

使用特定的底物通过脑匀浆上清液分光光度法对乙酰胆碱酯酶和β-分泌酶抑制进行了抑制研究。在东莨菪碱诱导的痴呆症小鼠模型中,通过高架十字迷宫和被动回避研究评估认知增强活性。使用 5,5'-二硫代双 2-硝基苯甲酸(5,5'-dithiobis 2-nitrobenzoic acid)从东莨菪碱诱导的健忘症小鼠脑上清液中分光光度法测量谷胱甘肽,在存在和不存在钩吻酊剂的情况下。

结果

与未处理的痴呆症组相比,钩吻对 AChE 和 β-分泌酶具有显著的抑制作用,IC50 分别为 9.25 和 16.25μg/ml,随后谷胱甘肽水平升高。通过测量行为参数和脑的抗氧化状态来确定钩吻对东莨菪碱(1mg/kg i.p.)注射致健忘症小鼠的认知缺陷的影响。钩吻在体内显著显示出抗痴呆活性(60%的保护作用)并增加了探索行为。

结论

我们的研究表明,富含生物碱、环烯醚萜和香豆素的再体制剂钩吻酊提取物在短期口服治疗后可显著增强成年小鼠的认知能力。因此,钩吻可以成为一种有前途的抗痴呆药物,通过双重抑制乙酰胆碱酯酶(无假阳性效应)、β-分泌酶和抗氧化活性来介导对健忘症、注意力障碍和学习功能障碍的保护。

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