Oleuropein aglycone and polyphenols from olive mill waste water ameliorate cognitive deficits and neuropathology

Br J Clin Pharmacol. 2017 Jan;83(1):54-62. doi: 10.1111/bcp.12993. Epub 2016 May 21.

Abstract

Aim: In TgCRND8 (Tg) mice we checked the dose-response effect of diet supplementation with oleuropein aglycone (OLE) at 12.5 or 0.5 mg kg-1 of diet. We also studied the effects of dietary intake of the mix of polyphenols present in olive mill waste water administered at a total dose as high as the highest dose of OLE (50 mg kg-1 of diet) previously investigated.

Methods: Four month-old Tg mice were equally divided into four groups and treated for 8 weeks with a modified low fat (5.0%) AIN-76 A diet (10 g day-1 per mouse) as such, supplemented with OLE (12.5 or 0.5 mg kg-1 of diet) or with a mix of polyphenols (50 mg kg-1 of diet) found in olive mill waste water. Behavioural performance was evaluated by the step down inhibitory avoidance and object recognition tests. Neuropathology was analyzed by immunohistochemistry.

Results: OLE supplementation at 12.5 mg kg-1 of diet and the mix of polyphenols was found to improve significantly cognitive functions of Tg mice (P < 0.0001). Aß42 and pE-3Aß plaque area and number were significantly reduced in the cortex by OLE and in the cortex and hippocampus by the mix of polyphenols (P < 0.01, P < 0.001 and P < 0.0001). Similar autophagy induction was found in the brain cortex of differently treated mice.

Conclusion: Our results extend previous data showing that the effects of OLE on behavioural performance and neuropathology are dose-dependent and not closely related to OLE by itself. In fact, diet supplementation with the same dose of a mix of polyphenols found in olive mill waste water resulted in comparable neuroprotection.

Keywords: Alzheimer's disease; amyloid plaques; authophagy; memory function; oleuropein aglycone; olive polyphenols.

Publication types

  • Review

MeSH terms

  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Behavior, Animal / drug effects
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / pathology
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / metabolism
  • Cognitive Dysfunction / pathology
  • Dietary Supplements
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Iridoid Glucosides
  • Iridoids / isolation & purification
  • Iridoids / therapeutic use*
  • Mice, Transgenic
  • Olea / chemistry*
  • Peptide Fragments / metabolism
  • Plaque, Amyloid / drug therapy*
  • Plaque, Amyloid / metabolism
  • Plaque, Amyloid / pathology
  • Polyphenols / isolation & purification
  • Polyphenols / therapeutic use*
  • Wastewater / chemistry

Substances

  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Iridoid Glucosides
  • Iridoids
  • Peptide Fragments
  • Polyphenols
  • Waste Water
  • amyloid beta-protein (1-42)
  • oleuropein