Boletus aereus protects against acute alcohol-induced liver damage in the C57BL/6 mouse via regulating the oxidative stress-mediated NF-κB pathway

Pharm Biol. 2020 Dec;58(1):905-914. doi: 10.1080/13880209.2020.1812672.

Abstract

Context: Alcoholic liver disease, caused by abuse and consumption of alcohol, exhibits high morbidity and mortality. Boletus aereus Bull. (Boletaceae) (BA) shows antioxidant, anti-inflammatory and antimicrobial effects.

Objectives: To investigate the hepatoprotective effects of BA using an acute alcohol-induced hepatotoxicity mice model.

Materials and methods: The composition of BA fruit body was first systematically analyzed. Subsequently, a C57BL/6 mice model of acute alcohol-induced liver injury was established by intragastrically administration of alcohol, which was intragastrically received with BA powder at 200 mg/kg and 800 mg/kg for 2 weeks, 60 mg/kg silybin treatment was used as positive control group. By employing the pathological examination, ELISA, RT-PCR and western blot, the regulation of BA on oxidative stress signals was investigated.

Results: The LD50 of BA was much higher than 4 g/kg/p.o. In acute alcohol-damaged mice, BA reduced the levels of alanine aminotransferase (>18.3%) and aspartate aminotransferase (>27.6%) in liver, increased the activity of liver alcohol dehydrogenase (>35.0%) and serum acetaldehyde dehydrogenase (>18.9%). BA increased the activity of superoxide dismutase (>13.4%), glutathione peroxidase (>11.0%) and 800 mg/kg BA strongly reduced chemokine (C-X-C motif) ligand 13 (14.9%) and chitinase-3 like-1 protein (13.4%) in serum. BA reversed mRNA over-expression (>70%) and phosphor-stimulated expression (>45.0%) of an inhibitor of nuclear factor κ-B kinase (NF-κB, an inhibitor of nuclear factor κ-B α and nuclear factor κ-B in the liver.

Conclusions: BA is effective in ameliorating alcohol-induced liver injury through regulating oxidative stress-mediated NF-κB signalling, which provides a scientific basis for further research on its clinical applications.

Keywords: Hepatoprotective; alcohol metabolism; inflammation; reactive oxygen species.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents
  • Antioxidants
  • Basidiomycota
  • Chemical and Drug Induced Liver Injury / pathology*
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / pathology
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Liver Diseases, Alcoholic
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Models, Animal
  • NF-kappa B / metabolism*
  • Oxidative Stress / drug effects
  • Protective Agents / pharmacology
  • Serum
  • Signal Transduction

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • NF-kappa B
  • Protective Agents

Supplementary concepts

  • Boletus aereus

Grants and funding

This work was supported by the Science and Technology Develop Project in Jilin Province of China under grant [No. 20191102027YY, 20200708091YY and 20200708068YY], the Special Projects of Cooperation between Jilin University and Jilin Province in China under grant [No. SXGJSF2017-1], Innovation Training Program of Zhuhai College of Jilin University under grant [No. 2018XJCQ016], and “Three levels” Talent Construction Projects in Zhuhai College of Jilin University.