Silibinin ameliorates Aβ25-35-induced memory deficits in rats by modulating autophagy and attenuating neuroinflammation as well as oxidative stress

Neurochem Res. 2017 Apr;42(4):1073-1083. doi: 10.1007/s11064-016-2141-4. Epub 2016 Dec 22.

Abstract

Alzheimer's disease (AD) is a progressive, neurodegenerative disease. Accumulating evidence suggests that inflammatory response, oxidative stress and autophagy are involved in amyloid β (Aβ)-induced memory deficits. Silibinin (silybin), a flavonoid derived from the herb milk thistle, is well known for its hepatoprotective activities. In this study, we investigated the neuroprotective effect of silibinin on Aβ25-35-injected rats. Results demonstrated that silibinin significantly attenuated Aβ25-35-induced memory deficits in Morris water maze and novel object-recognition tests. Silibinin exerted anxiolytic effect in Aβ25-35-injected rats as determined in elevated plus maze test. Silibinin attenuated the inflammatory responses, increased glutathione (GSH) levels and decreased malondialdehyde (MDA) levels, and upregulated autophagy levels in the Aβ25-35-injected rats. In conclusion, silibinin is a potential candidate for AD treatment because of its anti-inflammatory, antioxidant and autophagy regulating activities.

Keywords: Amyloid β; Autophagy; Inflammatory response; Oxidative stress; Silibinin.

MeSH terms

  • Amyloid beta-Peptides / toxicity*
  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Autophagy / drug effects*
  • Autophagy / physiology
  • Dose-Response Relationship, Drug
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Male
  • Memory Disorders / chemically induced*
  • Memory Disorders / drug therapy*
  • Memory Disorders / metabolism
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • Peptide Fragments / toxicity*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Silybin
  • Silymarin / pharmacology
  • Silymarin / therapeutic use*

Substances

  • Amyloid beta-Peptides
  • Antioxidants
  • Peptide Fragments
  • Silymarin
  • amyloid beta-protein (25-35)
  • Silybin