Protective effects of morin on lipopolysaccharide/d-galactosamine-induced acute liver injury by inhibiting TLR4/NF-κB and activating Nrf2/HO-1 signaling pathways

Int Immunopharmacol. 2017 Apr:45:148-155. doi: 10.1016/j.intimp.2017.02.010. Epub 2017 Feb 14.

Abstract

Morin, a bioactive flavonoid extracted from the bark of Moraceae plants and many medicinal herbs, has anti-inflammatory and antioxidative effects. In this research, we explored the protective effects of morin against lipopolysaccharide (LPS) and d-galactosamine (D-GalN) induced acute liver injury in mice. Mice were given an intraperitoneal injection of morin before LPS and D-GalN treatment and the HepG2 cells were only given morin to investigate its effects. The results showed that morin markedly inhibited the production of serum alanine transaminase (ALT), aspartate aminotransferase (AST), interleukin-6 (IL-6), tumor necrosis factor (TNF-α) and hepatic TNF-α, IL-6, and myeloperoxidase (MPO) induced by LPS/D-GalN. In order to evaluate morin effect in the future, we investigated the expression of nuclear factor E2 related factor 2 (Nrf2), nuclear factor-kappaB (NF-κB), toll like receptor 4 (TLR4) on liver injury. Taken together, these results suggested that morin could exert the anti-inflammatory and anti-oxidative effects against LPS/D-GalN-induced acute liver injury by activating Nrf2 signal pathways and inhibiting NF-κB activation.

Keywords: LPS/D-GalN; Morin; NF-κB; Nrf2.

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Aspartate Aminotransferases / blood
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Flavonoids / therapeutic use*
  • Galactosamine / immunology
  • Heme Oxygenase-1 / metabolism
  • Hep G2 Cells
  • Humans
  • Lipopolysaccharides / immunology
  • Liver / drug effects*
  • Liver / pathology
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Moraceae / immunology
  • NF-E2-Related Factor 2 / metabolism*
  • NF-kappa B / metabolism*
  • Signal Transduction / drug effects
  • Toll-Like Receptor 4 / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Flavonoids
  • Lipopolysaccharides
  • Membrane Proteins
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Nfe2l2 protein, mouse
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • Galactosamine
  • morin
  • Heme Oxygenase-1
  • Hmox1 protein, mouse
  • Aspartate Aminotransferases
  • Alanine Transaminase