Anti-depressive effect of polyphenols and omega-3 fatty acid from pomegranate peel and flax seed in mice exposed to chronic mild stress

Psychiatry Clin Neurosci. 2013 Nov;67(7):501-8. doi: 10.1111/pcn.12100. Epub 2013 Oct 24.


Aim: In this study polyphenols from pomegranate peel, and n-3 fatty acids with polyphenols from flax seed were evaluated for their anti depression properties in mice exposed to chronic mild stress (CMS).

Methods: A total of 40 mice initially trained to consume 2% sucrose solution for 3 weeks were then divided into five groups of eight each. The first group was the normal control, the remaining four groups were exposed to CMS but were force fed with either: 10 mL water per kg bodyweight per day; imipramine (a standard antidepressant) 15 mg kg bodyweight; 30 mg per kg bodyweight polyphenol equivalent extract from pomegranate peel; or 30 mg polyphenols per kg bodyweight with omega-3 fatty acids present, for 50 days. At the end, blood and brain were analyzed for various biomarkers of depression.

Results: The flax seed and imipramine groups had significantly increased sucrose consumption, decreased cortisol (blood), decreased epinephrine and norepinephrine concentration, decreased monoamine oxidase A and B activity, and decreased superoxide dismutase activity. Lipid peroxidation was completely inhibited. In contrast, pomegranate peel extract also completely inhibited lipid peroxidation in the brain, and reduced enzyme activity and hormone concentration but to a lesser extent than flax seed.

Conclusion: Polyphenols from flax seed with omega-3 fatty acids were able to reduce all the CMS effects tested compared to polyphenols from pomegranate peel.

Keywords: CMS; flax seed; neurotransmitters; pomegranate peel; sucrose.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use*
  • Behavior, Animal / drug effects
  • Brain / drug effects
  • Brain / metabolism
  • Depression / drug therapy*
  • Depression / etiology
  • Depression / metabolism
  • Depression / psychology
  • Fatty Acids, Omega-3 / pharmacology
  • Fatty Acids, Omega-3 / therapeutic use*
  • Flax
  • Lipid Peroxidation / drug effects
  • Lythraceae
  • Mice
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Polyphenols / pharmacology
  • Polyphenols / therapeutic use*
  • Stress, Psychological / complications*
  • Stress, Psychological / metabolism
  • Stress, Psychological / psychology
  • Superoxide Dismutase / metabolism


  • Antidepressive Agents
  • Fatty Acids, Omega-3
  • Plant Extracts
  • Polyphenols
  • Superoxide Dismutase