Biochanin A protects lipopolysaccharide/D-galactosamine-induced acute liver injury in mice by activating the Nrf2 pathway and inhibiting NLRP3 inflammasome activation

Int Immunopharmacol. 2016 Sep:38:324-31. doi: 10.1016/j.intimp.2016.06.009. Epub 2016 Jun 23.

Abstract

Biochanin A, an isoflavone existed in red clover and peanuts, has been reported to possess a wide spectrum of pharmacological activities, such as anti-inflammatory and antioxidant effects. However, the protective effects and mechanism of biochanin A on liver injury have not been reported. In this study, acute liver injury was induced by intraperitoneal injection of lipopolysaccharide (LPS) and d-galactosamine (D-GalN). Biochanin A was administrated 1h prior to LPS/D-GalN challenge. Serum ALT, AST, IL-1β, and TNF-α levels, hepatic malondialdehyde (MDA), GPx, SOD, and Catalase contents, tissue histology, IL-1β, TNF-α, NLRP3, and Nrf2 expression were detected. The results showed that serum ALT, AST, IL-1β, and TNF-α levels and hepatic MDA content increased after LPS/GalN treatment. These changes were attenuated by biochanin A. Meanwhile, biochanin A dose-dependently up-regulated the expression of Nrf2 and HO-1. Biochanin A also inhibited hepatic IL-1β and TNF-α expression in a dose-dependent manner. Biochanin A did not inhibit LPS/D-GalN-induced hepatic NLRP3, ASC, and caspase-1 expression. However, the interaction of NLRP3 with ASC and caspase-1 were inhibited by biochanin A. In addition, LPS/D-GalN-induced up-regulation of thioredoxin-interacting protein (TXNIP) and interaction between TXNIP and NLRP3 were also inhibited by biochanin A. In conclusion, biochanin A protected against LPS/GalN-induced liver injury by activating the Nrf2 pathway and inhibiting NLRP3 inflammasome activation.

Keywords: Biochanin A; LPS; NLRP3; Nrf2; TXNIP.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Chemical and Drug Induced Liver Injury / immunology
  • Galactosamine / immunology
  • Genistein / therapeutic use*
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism
  • Inflammasomes / drug effects*
  • Inflammasomes / metabolism
  • Interleukin-1beta / metabolism
  • Lipopolysaccharides / immunology
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Signal Transduction / drug effects
  • Thioredoxins / genetics
  • Thioredoxins / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Carrier Proteins
  • Inflammasomes
  • Interleukin-1beta
  • Lipopolysaccharides
  • Membrane Proteins
  • NF-E2-Related Factor 2
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nfe2l2 protein, mouse
  • Nlrp3 protein, mouse
  • Tumor Necrosis Factor-alpha
  • Txnip protein, mouse
  • Thioredoxins
  • Galactosamine
  • Genistein
  • Heme Oxygenase-1
  • Hmox1 protein, mouse
  • biochanin A