Caffeic acid improves locomotor activity and lessens inflammatory burden in a mouse model of rotenone-induced nigral neurodegeneration: Relevance to Parkinson's disease therapy

Pharmacol Rep. 2019 Feb;71(1):32-41. doi: 10.1016/j.pharep.2018.08.004. Epub 2018 Aug 11.

Abstract

Background: Caffeic acid phenethyl ester is found in honey bee propolis. It has immunomodulatory, anti-inflammatory and anti-cancer properties. Rotenone is a pesticide commonly used for inducing experimental Parkinson's disease (PD) due to complex I inhibition and microglia activating properties. The current study examined neuroprotective effect of caffeic acid against rotenone-induced neurodegeneration in groups of seven mice.

Methods: Mice received protective doses of caffeic acid (2.5, 5 or 10 mg/kg) daily and nine injections of rotenone (1 mg kg, subcutaneously) - every 48 h. Behavioral evaluation of motor function was done by a battery of tests including open-field test, cylinder test, pole test and rotarod test; all these tests showed motor impairment.

Results: Assay of striatal dopamine highlighted a significant decrease and increases in inflammatory markers. In addition, histopathological assessment of substantia nigra neurons demonstrated low immunostaining for tyrosine hydroxylase (TH) in rotenone treated mice. PCR analysis highlighted upregulation for genes encoding CD11b (a microglia surface antigen), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and nuclear factor-κB (NFκB). Treatment with caffeic acid (5 or 10 mg/kg) amended most of rotenone-induced motor deficits, lessened microglia expression and inflammatory mediators and improved the nigral TH immunostaining.

Conclusion: These results confirmed the anti-inflammatory activity of caffeic acid and highlighted its neuroprotective activity against rotenone-induced neurodegeneration in mice.

Keywords: Caffeic acid phenethyl ester; Inflammation; Mouse; Neurodegeneration; Rotenone.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antiparkinson Agents / pharmacology*
  • Apoptosis / drug effects
  • Behavior, Animal / drug effects*
  • CD11b Antigen / genetics
  • CD11b Antigen / metabolism
  • Caffeic Acids / pharmacology*
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Disease Models, Animal
  • Dopamine / metabolism
  • Inflammation Mediators / metabolism*
  • Locomotion / drug effects*
  • Male
  • Mice
  • Motor Activity / drug effects
  • NF-kappa B / metabolism
  • Neuroprotective Agents / pharmacology*
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Parkinsonian Disorders / chemically induced
  • Parkinsonian Disorders / drug therapy*
  • Parkinsonian Disorders / metabolism
  • Parkinsonian Disorders / psychology
  • Rotenone
  • Substantia Nigra / drug effects*
  • Substantia Nigra / metabolism
  • Substantia Nigra / pathology
  • Substantia Nigra / physiopathology
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antiparkinson Agents
  • CD11b Antigen
  • Caffeic Acids
  • Inflammation Mediators
  • NF-kappa B
  • Neuroprotective Agents
  • Rotenone
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Tyrosine 3-Monooxygenase
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • caffeic acid
  • Dopamine