Saikosaponin a ameliorates lipopolysaccharide and d‑galactosamine-induced liver injury via activating LXRα

Int Immunopharmacol. 2019 Jul:72:131-137. doi: 10.1016/j.intimp.2019.03.049. Epub 2019 Apr 10.

Abstract

Saikosaponin a (SSa), one of the major active components of Bupleurum falcatum, has antioxidant and anti-inflammatory pharmacological properties. However, the effects of SSa on liver injury have not been reported. In the present study, we evaluated the protective effects and mechanisms of SSa on lipopolysaccharide (LPS)/d‑galactosamine (D-GalN)-induced liver injury. The mice were pretreated with SSa 1 h before LPS/D-GalN treatment. The liver MPO, MDA, and the serum AST and ALT levels were tested by specific determination kits. The pro-inflammatory cytokines TNF-α and IL-1β were tested by ELISA kits. The expression of NF-κB signaling pathway and LXRα were tested by western blot analysis. The results showed that SSa significantly reduced the levels of liver MPO, MDA, and serum AST, ALT levels induced by LPS/D-GalN. SSa also dose-dependently inhibited LPS/D-GalN-induced pro-inflammatory cytokines TNF-α and IL-1β production. Furthermore, we found that SSa inhibited NF-κB signaling pathway activation induced by LPS/D-GalN. In addition, SSa dose-dependently increased the expression of LXRα. In conclusion, the results demonstrated that SSa had protective effect on liver injury and the anti-inflammatory mechanisms of SSa on LPS/D-GalN-induced liver injury may be due to its ability to increase LXRα expression. SSa might be a potential treatment for liver injury.

Keywords: LPS/D-GalN; LXRα; Saikosaponin a; liver injury.

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use*
  • Aspartate Aminotransferases / blood
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Chemical and Drug Induced Liver Injury / metabolism*
  • Chemical and Drug Induced Liver Injury / pathology
  • Galactosamine
  • Hep G2 Cells
  • Humans
  • Interleukin-1beta / metabolism
  • Lipopolysaccharides
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Liver X Receptors / metabolism*
  • Malondialdehyde / metabolism
  • Mice, Inbred C57BL
  • Oleanolic Acid / analogs & derivatives*
  • Oleanolic Acid / pharmacology
  • Oleanolic Acid / therapeutic use
  • Peroxidase / metabolism
  • Saponins / pharmacology*
  • Saponins / therapeutic use*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Interleukin-1beta
  • Lipopolysaccharides
  • Liver X Receptors
  • Saponins
  • Tnf protein, mouse
  • Tumor Necrosis Factor-alpha
  • Malondialdehyde
  • Oleanolic Acid
  • Galactosamine
  • Peroxidase
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • saikosaponin D