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作者

YU Li-li XU Li WANG Yi-nuo XUE Lu-ning Gou Ji-wei LI Hong-bo HOU Xue-qin ZHANG Han-ting

作者单位

Institute of Pharmacology,Taishan Medical University,Taian,271016,China；School of Science,China Pharmaceutical University,Nanjing,210009,China

刊名

神经药理学报

年份

2018

卷号

第8卷

期号

第4期

页码

7-8

ISSN

2095-1396

关键词

OSTHOLE ESTRADIOL Alzheimer’s disease OVARIECTOMIZED learning and memory

分类号

G

摘要

Objective:To investigate the effects of osthole,a natural coumarin first derived from the Cnidium plant,on learning and memory,physiological and pathological changes,and expression of estrogen receptor(ER)αandβin the brain of ovariectomized(OVX)rats of Alzheimer’s disease(AD)models.Methods:Female rats were randomly divided into six groups:①sham operation,and OVX plus:②saline,③Estradiol(0.1 mg·kg-1;positive control),④osthole at 12.5 mg·kg-1,⑤osthole at 25 mg·kg-1,and⑥osthole at 50 mg·kg-1;intraga...更多

Objective:To investigate the effects of osthole,a natural coumarin first derived from the Cnidium plant,on learning and memory,physiological and pathological changes,and expression of estrogen receptor(ER)αandβin the brain of ovariectomized(OVX)rats of Alzheimer’s disease(AD)models.Methods:Female rats were randomly divided into six groups:①sham operation,and OVX plus:②saline,③Estradiol(0.1 mg·kg-1;positive control),④osthole at 12.5 mg·kg-1,⑤osthole at 25 mg·kg-1,and⑥osthole at 50 mg·kg-1;intragastric administration for 30 days.The Morris water-maze test was used to evaluate the learning and memory ability of rats,ELISA to measure the levels of estradiol in the serum,Western blotting to detect the expression of ERαand ERβin the hippocampus,and HE staining to determine the histopathological changes in the brain.Results:①Effects on learning and memory:compared to the OVX alone,osthole at 25 or 50 mg·kg-1 signifi cantly increased the number of entries and the duration in the target quadrant in the water-maze probe trial test(P<0.05).②Effects on the estrogen pathway in the brain:the level of estradiol in the serum and expression of ERβin the hippocampus in the OVX alone were signifi cantly lower,while the expression of ERαwas higher,relative to the sham operation control(P<0.01);osthole at 25 mg·kg-1 reversed the OVX-induced changes in expression of ERαand ERβ(P<0.01).③Effects on histopathological change in the brain:in comparison with the sham operation group,the OVX rats treated with saline displayed increases in the number of apoptotic cells in the hippocampus,which was reversed by osthole at 25 or 50 mg·kg-1(P<0.05),but not the lower dose of 12.5 mg·kg-1.Conclusion:Osthole produced enhancement of learning and memory in the ovariectomized dementia model,which was mediated,at least in part,by regulating neuronal apoptosis and the estrogen pathway.Therefore,osthole is potent in delaying the development of female neurodegenerative diseases,which provides a potential,new approach to收起

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