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Effect of miroestrol on ovariectomy-induced cognitive impairment and lipid peroxidation in mouse brain

francis_鱼哥添加于 2014-8-31 21:00 | 1609 次阅读 | 0 个评论

作者
Monthakantirat O, Sukano W, Umehara K, Noguchi H, Chulikhit Y, Matsumoto K
摘要
Miroestrol (MR) is a phytoestrogen isolated from Pueraria candollei var. mirifica (KwaoKrueaKhao), a Thai medicinal plant used for rejuvenation. We examined the effects of MR on cognitive function, oxidative brain damage, and the expression of genes encoding brain-derived neurotrophic factor (BDNF) and cyclic AMP-responsive element-binding protein (CREB), factors implicated in neurogenesis and synaptic plasticity, in ovariectomized (OVX) mice. OVX decreased serum 17beta-estradiol level and uterine weight. OVX also impaired object recognition performance in the novel object recognition test and spatial cognitive performance in the Y-maze test and the water maze test. Daily treatment of MR dose-dependently attenuated OVX-induced cognitive dysfunction. Moreover, OVX mice had a significantly increased level of thiobarbituric acid-reactive substances, and down-regulated expression levels of BDNF and CREB mRNAs in the hippocampus and frontal cortex. MR treatment as well as hormone replacement therapy with 17beta-estradiol significantly reversed these neurochemical alterations caused by OVX. These results suggest that MR ameliorates cognitive deficits in OVX animals via attenuation of OVX-induced oxidative stress and down-regulation of BDNF and CREB mRNA transcription in the brain. Our findings raise the possibility that MR and Pueraria candollei var. mirifica, the plant of origin of MR, may have a beneficial effect on cognitive deficits like AD in which menopause/ovariectomy are implicated as risk factors.
详细资料
- 关键词: Cognitive dysfunction; Miroestrol; Ovariectomy; Oxidative stress; Pueraria candollei var. mirifica
- 文献种类: Journal Article
- 期刊名称: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology
- 期刊缩写: Phytomedicine
- 期卷页: 2014年第21卷第11期 1249-1255页
- 地址: Division of Medicinal Pharmacology, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan
- ISBN: 0944-7113
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