Antidepressant-like effects of paeoniflorin on post-stroke depression in a rat model

Neurol Res. 2019 May;41(5):446-455. doi: 10.1080/01616412.2019.1576361. Epub 2019 Feb 13.

Abstract

Background: Post-stroke depression (PSD) is one of the most prevalent emotional disorders after stroke and often results in poor outcomes. However, the underlying physiopathologic mechanism and effective treatment of PSD remain poorly elucidated.

Objective: To investigate whether paeoniflorin has antidepressant-like activity in a rat model of PSD.

Methods: Rats were randomly divided into four groups: sham-operated control (Sham), PSD, paeoniflorin (with PSD) and fluoxetine group(with PSD). PSD was developed by the right middle cerebral artery occlusion followed 21 days chronic unpredictable mild stress combined (CUMS) with raised alone. Tests of sucrose preference and open field were used to assess the depression-like behavior. Neurological function was evaluated by neurological deficit score and beam balance test. Expression of phosphorylated CREB (p-CREB) and brain-derived neurotrophic factor (BDNF) in the CA1 region of the hippocampal complex was evaluated by western blot and immunofluorescence.

Results: Te depressive-like behaviors markedly improved after paeoniflorin and fluoxetine treatment. Furthermore, paeoniflorin treatment significantly increased BDNF and p-CREB expression in the CA1 region.

Conclusions: Observed results suggested that paeoniflorin could ameliorate the symptoms and improve the functional capability of PSD rats, similar to the effect of fluoxetine.

Abbreviations: PSD: post-stroke depression; CUMS: chronic unpredictable mild stress stimulation; MCAO: middle cerebral artery occlusion; OFT: open field test; SPT: sucrose preference test, NDS: neurological deficit score, BBT: beam balance test; BDNF: brain-derived neurotrophic factor protein; p-CREB: phosphorylated Cyclic-AMP responsive element binding protein.

Keywords: BDNF; Post-stroke depression; fluoxetine; p-CREB; paeoniflorin.

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology*
  • Brain-Derived Neurotrophic Factor / metabolism
  • CA1 Region, Hippocampal / drug effects
  • CA1 Region, Hippocampal / metabolism
  • CA1 Region, Hippocampal / pathology
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / etiology*
  • Depressive Disorder / pathology
  • Depressive Disorder / physiopathology
  • Disease Models, Animal
  • Fluoxetine / pharmacology
  • Glucosides / pharmacology*
  • Male
  • Monoterpenes / pharmacology*
  • Random Allocation
  • Rats, Sprague-Dawley
  • Stress, Psychological / complications
  • Stress, Psychological / drug therapy
  • Stress, Psychological / pathology
  • Stress, Psychological / physiopathology
  • Stroke / complications*
  • Stroke / drug therapy
  • Stroke / pathology
  • Stroke / physiopathology

Substances

  • Antidepressive Agents
  • Bdnf protein, rat
  • Brain-Derived Neurotrophic Factor
  • Creb1 protein, rat
  • Cyclic AMP Response Element-Binding Protein
  • Glucosides
  • Monoterpenes
  • Fluoxetine
  • peoniflorin