Caffeic acid attenuates lipopolysaccharide-induced sickness behaviour and neuroinflammation in mice.
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.
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal 576104, India.
Sanchari
S
Basu Mallik
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal 576104, India.
Jayesh
J
Mudgal
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal 576104, India.
Madhavan
M
Nampoothiri
Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia; School of Pharmacy, Griffith University, Gold Coast, Australia.
Susan
S
Hall
Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia; School of Pharmacy, Griffith University, Gold Coast, Australia.
Shailendra Anoopkumar-
SA
Dukie
Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia; School of Pharmacy, Griffith University, Gold Coast, Australia.
Gary
G
Grant
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal 576104, India.
C Mallikarjuna
CM
Rao
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal 576104, India; Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia; School of Pharmacy, Griffith University, Gold Coast, Australia. Electronic address: d.arora@griffith.edu.au.
Devinder
D
Arora
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002109:Caffeic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D055809:Illness Behavior / Q000187:drug effects*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D002109:Caffeic Acids; D016207:Cytokines; D008070:Lipopolysaccharides; C040048:caffeic acid
Anti-oxidant; Caffeic acid; Cytokines; Neuroinflammation; Sickness behaviour