Estrogen Receptors Are Involved in the Neuroprotective Effect of Silibinin in Aβ1-42-Treated Rats

Neurochem Res. 2018 Apr;43(4):796-805. doi: 10.1007/s11064-018-2481-3. Epub 2018 Feb 3.

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease that is characterized by a cascade of pathologic changes. A widely discussed theory indicates that amyloid β (Aβ) peptides are the causative agents of AD. Silibinin, a flavonoid derived from milk thistle, is well known for its hepato-protective activities and we have reported the neuroprotective effects of silibinin. In this study, we investigated the role of estrogen receptors (ERs) in silibinin's neuroprotective effect on Aβ1-42-injected rats. Results of Morris water maze and novel object-recognition tests demonstrated that silibinin significantly attenuated Aβ1-42-induced memory impairment. Silibinin attenuated ERs and PI3K-Akt pathways, as well as modulated mitogen-activated protein kinases in the hippocampus of Aβ1-42-injected rats. Taken together, silibinin is a potential candidate in the treatment of Alzheimer's disease.

Keywords: Alzheimer’s disease; Amyloid; Estrogen receptor; Memory impairment; Silibinin.

MeSH terms

  • Amyloid beta-Peptides / toxicity*
  • Animals
  • Antioxidants / therapeutic use
  • Dose-Response Relationship, Drug
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Memory Disorders / chemically induced*
  • Memory Disorders / drug therapy*
  • Memory Disorders / metabolism
  • Neuroprotective Agents / therapeutic use*
  • Peptide Fragments / toxicity*
  • Rats
  • Receptors, Estrogen / physiology*
  • Silybin
  • Silymarin / therapeutic use*

Substances

  • Amyloid beta-Peptides
  • Antioxidants
  • Neuroprotective Agents
  • Peptide Fragments
  • Receptors, Estrogen
  • Silymarin
  • amyloid beta-protein (1-42)
  • Silybin