Tenuigenin ameliorates learning and memory impairments induced by ovariectomy

Physiol Behav. 2013 Jun 13:118:112-7. doi: 10.1016/j.physbeh.2013.05.025. Epub 2013 May 17.


Estrogen deficiency is associated with cognitive impairment. Hormone replacement therapy (HRT) has proven to be effective in preventing and reversing the memory and learning deficiencies. However, conventional estrogenic treatment could increase the risks of breast cancer and venous thromboembolism. Tenuigenin (TEN) is putatively believed as the active component extracted from a Chinese herb Polygala tenuifolia root. Although TEN has been shown to enhance learning and memory in healthy mice, it remains unknown whether or not TEN could ameliorate learning and memory impairments. In the present study, mice were divided into four groups: sham-operated (sham), ovariectomized (OVX), OVX+estradiol benzoate (EB) and OVX+TEN groups. Step-through passive avoidance and Y-maze tests were used to assess learning and memory abilities, and the number of nitric oxide synthase (NOS) positive neurons and the synaptic measurement of hippocampal CA1 area were examined. The results showed that TEN was given orally to OVX mice, leading to the improvement of learning and memory in step-through passive avoidance and Y-maze tests. TEN could reduce the loss of NOS positive neurons and prevent the synaptic morphological changes induced by ovariectomy. Our results suggest that TEN may exert a potential therapeutic value for menopause cognitive dysfunction.

Keywords: NOS positive neurons; Ovariectomy; Step-through passive avoidance test; Synaptic ultrastructure; Tenuigenin; Y-maze test.

MeSH terms

  • Animals
  • Avoidance Learning / physiology
  • CA1 Region, Hippocampal / drug effects
  • CA1 Region, Hippocampal / ultrastructure
  • Cognition Disorders / psychology
  • Drugs, Chinese Herbal / therapeutic use*
  • Estradiol / analogs & derivatives
  • Estradiol / pharmacology
  • Female
  • Learning Disabilities / drug therapy*
  • Learning Disabilities / etiology
  • Learning Disabilities / psychology*
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Memory Disorders / drug therapy*
  • Memory Disorders / etiology
  • Memory Disorders / psychology*
  • Mice
  • NADPH Dehydrogenase / metabolism
  • Ovariectomy / adverse effects*
  • Ovariectomy / psychology*
  • Psychomotor Performance / drug effects
  • Synapses / drug effects
  • Synapses / ultrastructure


  • Drugs, Chinese Herbal
  • tenuigenin
  • estradiol 3-benzoate
  • Estradiol
  • NADPH Dehydrogenase