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西红花酸减轻APPsw转基因小鼠的炎症和β-淀粉样蛋白积累。

Crocetin attenuates inflammation and amyloid-β accumulation in APPsw transgenic mice.

作者信息

Zhang Jin, Wang Yuchao, Dong Xueshuang, Liu Jianghua

机构信息

Department of Neurology, Daqing Oilfield General Hospitals, No. 9 Zhongkang Road, Daqing, 163001 China.

出版信息

Immun Ageing. 2018 Oct 30;15:24. doi: 10.1186/s12979-018-0132-9. eCollection 2018.

DOI:10.1186/s12979-018-0132-9
PMID:30450117
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6208089/
Abstract

BACKGROUND

Crocetin, an agent derived from saffron, has multiple pharmacological properties, such as neuroprotective, anti-oxidant, and anti-inflammatory actions. These properties might benefit the treatment of Alzheimer's disease (AD). In the present study, we tested whether crocetin attenuates inflammation and amyloid-β (Aβ) accumulation in APPsw transgenic mice, AD mouse models. Cell viability and the levels of Aβ40 and Aβ42 in HeLa cells stably transfected with Swedish mutant APP751 were evaluated. Mice with Swedish mutant APP751 transgene were used as transgenic mouse models of AD, and were orally administrated with crocetin. Aβ protein and inflammatory cytokines were measured with ELISA. NF-κB and P53 were measured with western blot assay. Learning and memory were analyzed with Morris water maze and novel object recognition tests.

RESULTS

Crocetin significantly reduced Aβ40 and Aβ42 secretion in Hela cells without effecting cell viability. In AD transgenic mice, crocetin significantly reduced the pro-inflammatory cytokines and enhanced anti-inflammatory cytokine in plasma, suppressed NF-κB activation and P53 expression in the hippocampus, decreased Aβ in various brain areas, and improved learning and memory deficits.

CONCLUSION

Crocetin improves Aβ accumulation-induced learning and memory deficit in AD transgenic mice, probably due to its anti-inflammatory and anti-apoptotic functions.

摘要

背景

藏红花素是一种从藏红花中提取的物质,具有多种药理特性,如神经保护、抗氧化和抗炎作用。这些特性可能对阿尔茨海默病(AD)的治疗有益。在本研究中,我们测试了藏红花素是否能减轻APPsw转基因小鼠(AD小鼠模型)中的炎症和β淀粉样蛋白(Aβ)积累。评估了稳定转染瑞典突变型APP751的HeLa细胞的细胞活力以及Aβ40和Aβ42的水平。将携带瑞典突变型APP751转基因的小鼠用作AD转基因小鼠模型,并对其口服给予藏红花素。用酶联免疫吸附测定法(ELISA)测量Aβ蛋白和炎性细胞因子。用蛋白质免疫印迹法检测核因子κB(NF-κB)和P53。用莫里斯水迷宫和新物体识别测试分析学习和记忆。

结果

藏红花素显著降低了HeLa细胞中Aβ40和Aβ42的分泌,而不影响细胞活力。在AD转基因小鼠中,藏红花素显著降低了血浆中的促炎细胞因子并增强了抗炎细胞因子,抑制了海马体中NF-κB的激活和P53的表达,降低了各个脑区的Aβ水平,并改善了学习和记忆缺陷。

结论

藏红花素改善了AD转基因小鼠中Aβ积累引起的学习和记忆缺陷,这可能归因于其抗炎和抗凋亡功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19f9/6208089/a4802f0d90a2/12979_2018_132_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19f9/6208089/745d41660cfa/12979_2018_132_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19f9/6208089/adc075c2c494/12979_2018_132_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19f9/6208089/46f1acb693eb/12979_2018_132_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19f9/6208089/f4de68360b26/12979_2018_132_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19f9/6208089/89d85efc95c0/12979_2018_132_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19f9/6208089/a4802f0d90a2/12979_2018_132_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19f9/6208089/745d41660cfa/12979_2018_132_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19f9/6208089/adc075c2c494/12979_2018_132_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19f9/6208089/46f1acb693eb/12979_2018_132_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19f9/6208089/f4de68360b26/12979_2018_132_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19f9/6208089/89d85efc95c0/12979_2018_132_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19f9/6208089/a4802f0d90a2/12979_2018_132_Fig6_HTML.jpg

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