Luteolin alleviates cognitive impairment in Alzheimer's disease mouse model via inhibiting endoplasmic reticulum stress-dependent neuroinflammation

被引:138
作者
Kou, Jie-jian [1 ]
Shi, Jun-zhuo [1 ]
He, Yang-yang [1 ]
Hao, Jiao-jiao [1 ]
Zhang, Hai-yu [1 ]
Luo, Dong-mei [1 ]
Song, Jun-ke [2 ,3 ]
Yan, Yi [4 ,5 ]
Xie, Xin-mei [1 ]
Du, Guan-hua [2 ,3 ]
Pang, Xiao-bin [1 ]
机构
[1] Henan Univ, Sch Pharm, Kaifeng 475004, Peoples R China
[2] Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Beijing 100050, Peoples R China
[3] Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, Natl Ctr Pharmaceut Screening, Beijing Key Lab Drug Target Identificat & Drug Sc, Beijing 100050, Peoples R China
[4] Ludwig Maximilians Univ Munchen, Inst Cardiovasc Prevent IPEK, D-80336 Munich, Germany
[5] DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, D-80336 Munich, Germany
基金
中国国家自然科学基金;
关键词
Alzheimer's disease; luteolin; neuroinflammation; endoplasmic reticulum stress; astrocyte; 3 x Tg-AD mice; C6; cells; UNFOLDED PROTEIN RESPONSE; TRANSGENIC MODEL; ER STRESS; PATHWAY; BETA; RATS;
D O I
10.1038/s41401-021-00702-8
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Luteolin is a flavonoid in a variety of fruits, vegetables, and herbs, which has shown anti-inflammatory, antioxidant, and anti-cancer neuroprotective activities. In this study, we investigated the potential beneficial effects of luteolin on memory deficits and neuroinflammation in a triple-transgenic mouse model of Alzheimer's disease (AD) (3 x Tg-AD). The mice were treated with luteolin (20, 40 mg center dot kg(-1) center dot d(-1), ip) for 3 weeks. We showed that luteolin treatment dose-dependently improved spatial learning, ameliorated memory deficits in 3 x Tg-AD mice, accompanied by inhibiting astrocyte overactivation (GFAP) and neuroinflammation (TNF-alpha, IL-1 beta, IL-6, NO, COX-2, and iNOS protein), and decreasing the expression of endoplasmic reticulum (ER) stress markers GRP78 and IRE1 alpha in brain tissues. In rat C6 glioma cells, treatment with luteolin (1, 10 mu M) dose-dependently inhibited LPS-induced cell proliferation, excessive release of inflammatory cytokines, and increase of ER stress marker GRP78. In conclusion, luteolin is an effective agent in the treatment of learning and memory deficits in 3 x Tg-AD mice, which may be attributable to the inhibition of ER stress in astrocytes and subsequent neuroinflammation. These results provide the experimental basis for further research and development of luteolin as a therapeutic agent for AD.
引用
收藏
页码:840 / 849
页数:10
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