Caffeic acid attenuates lipopolysaccharide-induced sickness behaviour and neuroinflammation in mice

Neurosci Lett. 2016 Oct 6:632:218-23. doi: 10.1016/j.neulet.2016.08.044. Epub 2016 Sep 3.

Abstract

Accumulating data links inflammation, oxidative stress and immune system in the pathophysiology of major depressive disorders. Sickness behaviour is a set of behavioural changes that develop during infection, eventually leading to decrease in mobility and depressed behaviour. Lipopolysaccharide (LPS) induces a depression-like state in animals that mimics sickness behaviour. Caffeic acid, a naturally occurring polyphenol, possesses antioxidant and anti-inflammatory properties. The present study was designed to explore the potential of caffeic acid against LPS-induced sickness behaviour in mice. Caffeic acid (30mg/kg) and imipramine (15mg/kg) were administered orally one hour prior to LPS (1.5mg/kg) challenge. Behavioural assessment was carried out between 1 and 2h and blood samples were collected at 3h post-LPS injection. Additionally, cytokines (brain and serum) and brain oxidative stress markers were estimated. LPS increased the systemic and brain cytokine levels, altered the anti-oxidant defence and produced key signs of sickness behaviour in animals. Caffeic acid treatment significantly reduced the LPS-induced changes, including reduced expression of inflammatory markers in serum and whole brain. Caffeic acid also exerted an anti-oxidant effect, which was evident from the decreased levels of oxidative stress markers in whole brain. Our data suggests that caffeic acid can prevent the neuroinflammation-induced acute and probably the long term neurodegenerative changes.

Keywords: Anti-oxidant; Caffeic acid; Cytokines; Neuroinflammation; Sickness behaviour.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Antioxidants / pharmacology*
  • Antioxidants / therapeutic use
  • Behavior, Animal / drug effects*
  • Brain / drug effects*
  • Brain / metabolism
  • Caffeic Acids / pharmacology*
  • Caffeic Acids / therapeutic use
  • Cytokines / metabolism
  • Illness Behavior / drug effects*
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Lipopolysaccharides
  • Male
  • Mice
  • Oxidative Stress / drug effects

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Caffeic Acids
  • Cytokines
  • Lipopolysaccharides
  • caffeic acid