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

Phytomedicine. 2014 Sep 25;21(11):1249-55. doi: 10.1016/j.phymed.2014.06.012. Epub 2014 Jul 25.


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.

Keywords: Cognitive dysfunction; Miroestrol; Ovariectomy; Oxidative stress; Pueraria candollei var. mirifica.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cognition / drug effects*
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Estradiol / blood
  • Female
  • Lipid Peroxidation / drug effects*
  • Maze Learning / drug effects
  • Mice
  • Ovariectomy
  • Plant Bark / chemistry
  • Pueraria / chemistry*
  • Steroids / pharmacology*
  • Uterus / drug effects


  • Brain-Derived Neurotrophic Factor
  • Cyclic AMP Response Element-Binding Protein
  • Steroids
  • miroestrol
  • Estradiol