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光果甘草黄酮类抗氧化剂对戊四氮点燃小鼠苯妥英钠诱导的认知缺陷的保护作用

Protective effect on phenytoin-induced cognition deficit in pentylenetetrazol kindled mice: A repertoire of Glycyrrhiza glabra flavonoid antioxidants.

作者信息

Singh Paramdeep, Singh Damanpreet, Goel Rajesh K

机构信息

a Department of Pharmacology , Chitkara College of Pharmacy, Chitkara University , Patiala , Punjab , India and.

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

出版信息

Pharm Biol. 2016 Jul;54(7):1209-18. doi: 10.3109/13880209.2015.1063673. Epub 2015 Jul 8.

Abstract

CONTEXT

Glycyrrhiza glabra L. (Febaceae) has been widely used in traditional medicine and scientifically explored for its anticonvulsant and memory improving potential.

OBJECTIVE

The objective of this study is to investigate the effect of flavonoid rich fraction of G. glabra root extract against phenytoin-induced cognition deficit in pentylenetetrazol (PTZ) kindled mice.

MATERIALS AND METHODS

The ethyl acetate fraction was initially screened in different in vitro free radical scavenging assays. For in vivo studies, the kindled mice in different groups were given 15 d post-treatment with phenytoin (25 mg/kg; p.o.) per se or in combination with varying doses of the fraction (5, 10, and 15 mg/kg; p.o.). Seizure severity score and cognitive functions were accessed using Racine's scale and passive shock avoidance paradigm, respectively on every 5th d after a PTZ challenge dose (35 mg/kg; i.p.). At the end of study, the animals were scarified for cerebral biochemistry.

RESULTS

The fraction showed marked antioxidant activity indicated by low IC50 values in DPPH (20.9 µg/mL), nitric oxide radical scavenging (195.2 µg/mL), and capacity of hydrogen peroxide scavenging (3.4 µg/mL) assays. Treatment with phenytoin per se and along with the flavonoid rich fraction showed significant reduction in seizure severity score as compared to vehicle control. The combined-treated groups also showed improved cognitive functions indicated by reduced number of mistakes and increased step-down latency in passive shock avoidance paradigm.

CONCLUSION

From the results, it can be concluded that the flavonoid rich fraction in combination with phenytoin reduces seizure severity and improve cognitive functions in PTZ-kindled mice.

摘要

背景

光果甘草(豆科)在传统医学中已被广泛应用,并对其抗惊厥和改善记忆的潜力进行了科学探索。

目的

本研究旨在探讨光果甘草根提取物富含黄酮的部分对苯妥英钠诱导的戊四氮(PTZ)点燃小鼠认知缺陷的影响。

材料与方法

乙酸乙酯部分最初在不同的体外自由基清除试验中进行筛选。对于体内研究,不同组的点燃小鼠在治疗15天后单独给予苯妥英钠(25mg/kg;口服)或与不同剂量的该部分(5、10和15mg/kg;口服)联合使用。在PTZ激发剂量(35mg/kg;腹腔注射)后每5天分别使用Racine量表和被动回避电击范式评估癫痫发作严重程度评分和认知功能。在研究结束时,处死动物进行脑生化分析。

结果

该部分在DPPH(20.9μg/mL)、一氧化氮自由基清除(195.2μg/mL)和过氧化氢清除能力(3.4μg/mL)试验中表现出显著的抗氧化活性,IC50值较低。与赋形剂对照组相比,单独使用苯妥英钠以及与富含黄酮的部分联合治疗均显著降低了癫痫发作严重程度评分。联合治疗组在被动回避电击范式中也表现出认知功能改善,表现为错误数量减少和步下潜伏期增加。

结论

从结果可以得出结论,富含黄酮的部分与苯妥英钠联合使用可降低PTZ点燃小鼠的癫痫发作严重程度并改善认知功能。

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