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诃子果实单宁酸通过调节神经递质来减轻 GABA 拮抗剂引起的焦虑样行为。

Tannins from Terminalia chebula fruits attenuates GABA antagonist-induced anxiety-like behaviour via modulation of neurotransmitters.

机构信息

Defence Food Research Laboratory, Applied Nutrition Division, DRDO, Mysore, India.

出版信息

J Pharm Pharmacol. 2018 Dec;70(12):1662-1674. doi: 10.1111/jphp.13007. Epub 2018 Sep 10.

DOI:10.1111/jphp.13007
PMID:30198561
Abstract

OBJECTIVES

This article investigates the anxiolytic activity of Terminalia chebula tannin-rich extract against picrotoxin (PTX; GABA antagonist)-induced anxiety in mice model.

METHODS

Anxiolytic activity was studied by elevated plus maze (EPM), open field test (OFT), light/dark box test (LDT) and Vogel's conflict test (VCT). Electroencephalogram (EEG) was performed to know the changes in brain activity instigated by GABA antagonist. 5-hydroxytryptamine (5-HT), dopamine and norepinephrine levels in brain tissues were estimated by HPLC. The mRNA (CREB, BDNF, GABA, and 5-HT ) and protein expression (CREB, p-CREB, BDNF, ERK ½, p-ERK ½, GABA Rα1, 5-HT and GAPDH) levels in brain tissue were determined by RT-PCR and Western blot analysis, respectively.

KEY FINDINGS

Terminalia chebula tannin-rich extract (TCHE) supplementation increased locomotion in mice towards open arm (EPM), time spent in illuminated area (LDT), rearing frequency (OFT) and number of shocks (VCT) compared to PTX (P < 0.05). Furthermore, TCHE down-regulated serum cortisol levels and showed increased levels of 5-HT, DA and NE. Gene expressions such as BDNF, CREB, GABA and 5-HT were up-regulated by TCHE treatment compared to PTX.

CONCLUSIONS

Terminalia chebula tannin-rich extract showed significant anxiolytic activity against picrotoxin and could be used as natural therapy in neurodegenerative disorders.

摘要

目的

本研究旨在探讨诃子单宁丰富提取物对戊四氮(GABA 拮抗剂)诱导的小鼠焦虑模型的抗焦虑作用。

方法

采用高架十字迷宫(EPM)、旷场试验(OFT)、明暗箱试验(LDT)和Vogel 冲突试验(VCT)研究抗焦虑活性。通过脑电图(EEG)了解 GABA 拮抗剂引起的大脑活动变化。通过 HPLC 测定脑组织中 5-羟色胺(5-HT)、多巴胺和去甲肾上腺素的水平。采用 RT-PCR 和 Western blot 分析分别测定脑组织中 mRNA(CREB、BDNF、GABA 和 5-HT)和蛋白表达(CREB、p-CREB、BDNF、ERK ½、p-ERK ½、GABA Rα1、5-HT 和 GAPDH)水平。

主要发现

与 PTX 相比,诃子单宁丰富提取物(TCHE)补充剂增加了小鼠在 EPM 中的开放臂(EPM)、LDT 中的光照区域时间、OFT 中的活动频率和 VCT 中的电击次数(P < 0.05)。此外,TCHE 降低了血清皮质醇水平,增加了 5-HT、DA 和 NE 的水平。与 PTX 相比,TCHE 处理上调了 BDNF、CREB、GABA 和 5-HT 等基因的表达。

结论

诃子单宁丰富提取物对戊四氮表现出显著的抗焦虑作用,可作为神经退行性疾病的天然治疗方法。

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