title: Effect of miroestrol on ovariectomy-induced cognitive impairment and lipid peroxidation in mouse brain.
abstract: 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 17β-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 17β-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.
authors.affiliation: Division of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Orawan
authors.initials: O
authors.lastname: Monthakantirat
authors.affiliation: Division of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Wichitsak
authors.initials: W
authors.lastname: Sukano
authors.affiliation: Department of Pharmacognosy, School of Pharmaceutical Sciences, University of Shizuoka, Yada 52-1, Shizuoka-shi, Shizuoka 422-8526, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Umehara
authors.affiliation: Department of Pharmacognosy, School of Pharmaceutical Sciences, University of Shizuoka, Yada 52-1, Shizuoka-shi, Shizuoka 422-8526, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Noguchi
authors.affiliation: Division of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, Thailand; Division of Medicinal Pharmacology, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. Electronic address: yaosum@kku.ac.th.
authors.forename: Yaowared
authors.initials: Y
authors.lastname: Chulikhit
authors.affiliation: Division of Medicinal Pharmacology, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Kinzo
authors.initials: K
authors.lastname: Matsumoto
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003071:Cognition / Q000187:drug effects*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004958:Estradiol / Q000097:blood; D005260:Female; D015227:Lipid Peroxidation / Q000187:drug effects*; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D010052:Ovariectomy; D024301:Plant Bark / Q000737:chemistry; D029908:Pueraria / Q000737:chemistry*; D013256:Steroids / Q000494:pharmacology*; D014599:Uterus / Q000187:drug effects
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D013256:Steroids; C571572:miroestrol; D004958:Estradiol
keywords: Cognitive dysfunction; Miroestrol; Ovariectomy; Oxidative stress; Pueraria candollei var. mirifica