Saikosaponin‑D improves fear memory deficits in ovariectomized rats via the action of estrogen receptor‑α in the hippocampus

Mol Med Rep. 2019 Jul;20(1):332-340. doi: 10.3892/mmr.2019.10232. Epub 2019 May 10.

Abstract

Saikosaponin‑D (SSD), which is the main bioactive component in the traditional Chinese medicine Chai Hu (Bupleurum falcatum L), possesses estrogen‑like properties and is widely used in treating estrogen‑related neurological disorders. The current study aimed to investigate the protective effects of SSD on the fear memory deficit in ovariectomized (OVX) rats and the potential underlying mechanism. SSD treatment significantly prolonged freezing time in OVX rats in a manner similar to that of estradiol (E2), whereas this effect was markedly suppressed by co‑administration of ICI182780, a non‑selective estrogen receptor (ER) inhibitor. The expression of ERα in the hippocampus of OVX rats was significantly elevated by SSD; however, Erβ expression and E2 synthesis were not markedly affected by SSD treatment. Collectively, this study demonstrated that SSD‑mediated fear memory improvement in OVX rats may be attributed not to E2 levels or ERβ activity, but to ERα activation in the hippocampus.

MeSH terms

  • Animals
  • Bupleurum / chemistry
  • Estradiol / metabolism
  • Estrogen Receptor alpha / antagonists & inhibitors
  • Estrogen Receptor alpha / genetics*
  • Estrogen Receptor beta / antagonists & inhibitors
  • Estrogen Receptor beta / genetics*
  • Fear / drug effects*
  • Fear / physiology
  • Female
  • Fulvestrant / pharmacology
  • Gene Expression Regulation / drug effects
  • Hippocampus / drug effects
  • Hippocampus / pathology
  • Medicine, Chinese Traditional
  • Memory Disorders / drug therapy*
  • Memory Disorders / genetics
  • Memory Disorders / pathology
  • Oleanolic Acid / analogs & derivatives*
  • Oleanolic Acid / pharmacology
  • Ovariectomy
  • Rats
  • Saponins / pharmacology*
  • Temporal Lobe / drug effects
  • Temporal Lobe / pathology

Substances

  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Saponins
  • Fulvestrant
  • Estradiol
  • Oleanolic Acid
  • saikosaponin D