Geraniol protects against lipopolysaccharide and D-galactosamine-induced fulminant hepatic failure by activating PPARγ

Microb Pathog. 2019 Mar:128:7-12. doi: 10.1016/j.micpath.2018.11.054. Epub 2018 Dec 11.

Abstract

Geraniol (GOH), a natural component of plant essential oils, exhibits potent antioxidant and anti-inflammatory properties. The aim of this study was to assess the protective effects and mechanisms of GOH on lipopolysaccharide (LPS)/d-galactosamine (D-GalN)-induced fulminant hepatic failure (FHF). Mice were treated with GOH (12.5, 25, and 50 μg/kg) 1 h before challenging LPS (60 mg/kg) and D-GalN (800 mg/kg). 8 h later LPS/D-GlaN treatment, mice were sacrificed and the serum and the liver tissues were collected for testing. The liver pathological changes were assessed by H & E staining. MPO activity, MDA level in liver tissues, and AST, ALT levels in serum were detected by specific detection kits. The levels of TNF-α and IL-1β were detected by ELISA. The expression of NF-κB and PPARγ were detected by western blot analysis and qRT-PCR. The results showed that GOH had a protective effect on LPS/D-GalN-induced FHF, as evidence by the attenuation of liver pathological injury, MPO activity, MDA level, and serum AST and ALT levels. GOH reduced liver TNF-α and IL-1β levels through inhibiting NF-κB signaling pathway activation. Furthermore, GOH increased PPARγ expression in FHF induced by LPS/D-GalN. In conclusion, the present study proved that GOH protects against LPS/D-GalN-induced FHF through inhibiting inflammatory response and increasing PPARγ expression.

Keywords: Fulminant hepatic failure; Geraniol; Lipopolysaccharide; NF-κB; PPARγ; d-galactosamine.

MeSH terms

  • Acyclic Monoterpenes
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Antioxidants / pharmacology
  • Disease Models, Animal
  • Galactosamine / adverse effects*
  • Interleukin-1beta / metabolism
  • Lipopolysaccharides / adverse effects*
  • Liver / chemistry
  • Liver / injuries
  • Liver / pathology
  • Liver Failure, Acute / drug therapy*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism
  • Oils, Volatile / pharmacology
  • PPAR gamma / metabolism*
  • Plant Oils / pharmacology
  • Protective Agents / pharmacology*
  • Signal Transduction / drug effects
  • Terpenes / administration & dosage
  • Terpenes / pharmacology*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Acyclic Monoterpenes
  • Anti-Inflammatory Agents
  • Antioxidants
  • Interleukin-1beta
  • Lipopolysaccharides
  • NF-kappa B
  • Oils, Volatile
  • PPAR gamma
  • Plant Oils
  • Protective Agents
  • Terpenes
  • Tumor Necrosis Factor-alpha
  • Galactosamine
  • geraniol