Berberine mitigates cyclophosphamide-induced hepatotoxicity by modulating antioxidant status and inflammatory cytokines

J Cancer Res Clin Oncol. 2014 Jul;140(7):1103-9. doi: 10.1007/s00432-014-1665-8. Epub 2014 Apr 18.


Objectives: The present study was designed to investigate the possible protective effects of berberine against cyclophosphamide (CP)-induced hepatotoxicity in rats.

Methods: The experimental rats were treated with berberine orally at a dose of 50 mg/kg for 11 consecutive days after the administration of a single intraperitoneal dose of CP (200 mg/kg). The hepatoprotective effect of berberine was evaluated by assaying liver function markers, the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α), antioxidant defense system and gene expressions of both TNF-α and cyclooxygenase 2 (COX-2).

Results: The biochemical results showed that administration of CP induced hepatic damage associated with a significant increase in the serum marker enzymes aspartate and alanine transaminases (AST, ALT) and alkaline phosphatase (ALP), and a significant increase in serum total bilirubin accompanied with a decrease in serum albumin concentration. In addition, CP-administration induced oxidative stress in the liver as evident from the increased lipid peroxidation (LPO), declined glutathione (GSH) content and glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities. Moreover, administration of CP was associated with a significant increase in serum TNF-α. Similarly, CP administration was accompanied by a significant increase in the mRNA expression of both TNF-α and COX-2 in the liver as indicated by the qPCR assay. Concomitant administration of berberine efficiently alleviated the altered biochemical parameters.

Conclusion: Berberine showed a marked hepatoprotective effect against CP-induced hepatotoxicity through alleviation of the elevated serum marker enzymes in addition to its antioxidant and anti-inflammatory efficacies.

MeSH terms

  • Animals
  • Berberine / pharmacology*
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Cyclophosphamide / toxicity*
  • Cytokines / blood*
  • Cytoprotection*
  • Inflammation Mediators / blood*
  • Liver Function Tests
  • Male
  • Oxidative Stress / drug effects
  • Rats


  • Cytokines
  • Inflammation Mediators
  • Berberine
  • Cyclophosphamide