Protective effect of linalool against lipopolysaccharide/D-galactosamine-induced liver injury in mice

Int Immunopharmacol. 2014 Dec;23(2):523-9. doi: 10.1016/j.intimp.2014.10.001. Epub 2014 Oct 12.


Linalool, a natural compound of the essential oils, has been shown to have antinociceptive, antimicrobial, and anti-inflammatory properties. The aim of this study was to investigate the effects of linalool against lipopolysaccharide (LPS)/D-galactosamine (GalN)-induced liver injury in mice. Mice were administered with linalool 1h before receiving LPS (50 μg/kg) and GalN (800 mg/kg). The results demonstrated that linalool had a protective effect on LPS/GalN-induced acute liver injury, as evidenced by the attenuation of hepatic pathological damage, malondialdehyde (MDA) content, MPO activity and serum ALT and AST levels. Linalool alleviated serum and hepatic TNF-α and IL-6 production, as well as hepatic iNOS and COX-2 expression by inhibiting NF-κB activation. Treatment of linalool increased bcl-2 expression and inhibited caspase-3 and caspase-8 expression. In addition, linalool increased Nrf2 and heme oxygenase-1 expression up-regulation by LPS/GalN. In conclusion, our results suggested that linalool was protected against LPS/GalN-induced liver injury through induction of antioxidant defense via Nrf2 activating and reduction inflammatory response via NF-κB inhibition.

Keywords: Linalool; Lipopolysaccharide; NF-κB; Nrf2; d-Galactosamine.

MeSH terms

  • Acyclic Monoterpenes
  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / therapeutic use*
  • Chemical and Drug Induced Liver Injury / enzymology
  • Chemical and Drug Induced Liver Injury / immunology
  • Chemical and Drug Induced Liver Injury / pathology
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Cyclooxygenase 2 / blood
  • Cyclooxygenase 2 / metabolism
  • Galactosamine / toxicity*
  • Interleukin-6 / blood
  • Interleukin-6 / metabolism
  • Lipid Peroxidation / drug effects
  • Lipopolysaccharides / toxicity*
  • Liver Function Tests
  • Male
  • Mice, Inbred BALB C
  • Monoterpenes / administration & dosage
  • Monoterpenes / therapeutic use*
  • NF-E2-Related Factor 2 / metabolism
  • NF-kappa B / antagonists & inhibitors
  • Nitric Oxide Synthase Type II / blood
  • Nitric Oxide Synthase Type II / metabolism
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / metabolism


  • Acyclic Monoterpenes
  • Anti-Inflammatory Agents
  • Interleukin-6
  • Lipopolysaccharides
  • Monoterpenes
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Nfe2l2 protein, mouse
  • Tumor Necrosis Factor-alpha
  • interleukin-6, mouse
  • lipopolysaccharide, E coli O55-B5
  • Galactosamine
  • linalool
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2