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发酵姜黄对氧化应激诱导的C6胶质瘤细胞、促炎激活的BV2小胶质细胞以及东莨菪碱诱导的小鼠记忆障碍模型中记忆功能障碍的保护作用。

The protective effect of fermented Curcuma longa L. on memory dysfunction in oxidative stress-induced C6 gliomal cells, proinflammatory-activated BV2 microglial cells, and scopolamine-induced amnesia model in mice.

作者信息

Eun Cheong-Su, Lim Jong-Soon, Lee Jihye, Lee Sam-Pin, Yang Seun-Ah

机构信息

Major in Food Science and Technology, Keimyung University, Daegu, 42601, Republic of Korea.

The Center for Traditional Microorganism Resources, Keimyung University, Daegu, 42601, Republic of Korea.

出版信息

BMC Complement Altern Med. 2017 Jul 17;17(1):367. doi: 10.1186/s12906-017-1880-3.

Abstract

BACKGROUND

Curcuma longa L. is a well-known medicinal plant that has been used for its anti-cancer, neuroprotective, and hepatoprotective effects. However, the neuroprotective effect of fermented C. longa (FCL) has not been reported. Therefore, in this study, the effectiveness of FCL for the regulation of memory dysfunction was investigated in two brain cell lines (rat glioma C6 and murine microglia BV2) and scopolamine-treated mice.

METHODS

C. longa powder was fermented by 5% Lactobacillus plantarum K154 containing 2% (w/v) yeast extract at 30 °C for 72 h followed by sterilization at 121 °C for 15 min. The protective effects of fermented C. longa (FCL) on oxidative stress induced cell death were analyzed by MTT assay in C6 cells. The anti-inflammatory effects of FCL were investigated by measuring the production of nitric oxide (NO) and prostaglandin E (PGE) as well as the expression levels of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated BV2 cells. The step-through passive avoidance test, Morris water maze test, acetylcholinesterase (AChE) activity, and expression of cAMP response element-binding protein (CREB) and brain-derived neurotropic factor (BDNF) were employed to determine the effects of FCL on scopolamine-induced memory deficit in mice. The contents of curcuminoids were analyzed through LC/MS.

RESULTS

Pretreatment with FCL effectively prevented the cell death induced by oxidative stress in C6 cells. Moreover, FCL inhibited the production NO and PGE via the inhibition of iNOS and COX-2 expression in BV2 cells. FCL significantly attenuated scopolamine-induced memory impairment in mice and prevented scopolamine-induced AChE activity in the hippocampus. Additionally, FCL reversed the reduction of CREB and BDNF expression. The curcuminoids content in FCL was 1.44%.

CONCLUSION

FCL pretreatment could alleviate scopolamine-induced memory impairment in mice, as well as oxidative stress and inflammation in C6 and BV2 cells, respectively. Thus, FCL might be a useful material for preventing impairment of learning and memory.

摘要

背景

姜黄是一种著名的药用植物,其具有抗癌、神经保护和肝脏保护作用。然而,发酵姜黄(FCL)的神经保护作用尚未见报道。因此,在本研究中,我们在两种脑细胞系(大鼠胶质瘤C6和小鼠小胶质细胞BV2)以及东莨菪碱处理的小鼠中研究了FCL对记忆功能障碍的调节作用。

方法

将姜黄粉末用含有2%(w/v)酵母提取物的5%植物乳杆菌K154在30℃下发酵72小时,然后在121℃下灭菌15分钟。通过MTT法分析发酵姜黄(FCL)对氧化应激诱导的C6细胞死亡的保护作用。通过测量一氧化氮(NO)和前列腺素E(PGE)的产生以及脂多糖刺激的BV2细胞中诱导型NO合酶(iNOS)和环氧化酶-2(COX-2)的表达水平来研究FCL的抗炎作用。采用穿梭箱被动回避试验、莫里斯水迷宫试验、乙酰胆碱酯酶(AChE)活性以及环磷酸腺苷反应元件结合蛋白(CREB)和脑源性神经营养因子(BDNF)的表达来确定FCL对东莨菪碱诱导的小鼠记忆缺陷的影响。通过液相色谱/质谱分析姜黄素类化合物的含量。

结果

FCL预处理有效预防了C6细胞中氧化应激诱导的细胞死亡。此外,FCL通过抑制BV2细胞中iNOS和COX-2的表达来抑制NO和PGE的产生。FCL显著减轻了东莨菪碱诱导的小鼠记忆损伤,并预防了东莨菪碱诱导的海马体中AChE活性。此外,FCL逆转了CREB和BDNF表达的降低。FCL中姜黄素类化合物的含量为1.44%。

结论

FCL预处理可减轻东莨菪碱诱导的小鼠记忆损伤,以及分别减轻C6和BV2细胞中的氧化应激和炎症。因此,FCL可能是预防学习和记忆损伤的有用物质。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3b6/5514491/f65fb47bd149/12906_2017_1880_Fig1_HTML.jpg

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