Berberine mitigates methotrexate-induced oxidative stress and inflammation in the cerebrum of rats

Walaa G. Hozayen, Shimaa M. Ramadan, Abdulmannan Fadel, Ayman M. Mahmoud

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


Berberine is a natural isoquinoline alkaloid with multiple beneficial therapeutic effects. This study was designed to evaluate the protective effect of berberine against methotrexate (MTX)-induced oxidative stress and inflammation in the brain of rats. Rats received a single intraperitoneal injection of MTX (20 mg/kg) and orally administered 25 mg/kg and 50 mg/kg body weight berberine for 7 days. MTX-induced rats showed significantly increased lipid peroxidation and nitric oxide levels in the cerebrum. Treatment of the MTX-induced rats with berberine produced a significant decrease in cerebral levels of lipid peroxidation and nitric oxide. In addition, berberine induced a significant increase in reduced glutathione, superoxide dismutase, glutathione peroxidase and glutathione-S-transferase in the cerebrum of MTX-induced rats. Rats received MTX showed a significant up-regulation of nuclear factor-kappaB (NF-κB), inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α) and interleukin-1beta (IL-1β) expression in the cerebrum, an effect that was significantly reversed following treatment with berberine. In conclusion, berberine protects against MTX-induced neurotoxicity through attenuating oxidative stress and inflammation, and boosting the antioxidant defenses.

Original languageEnglish
Pages (from-to)43-49
Number of pages7
JournalJournal of Applied Pharmaceutical Science
Issue number11
Publication statusPublished - Nov 1 2017
Externally publishedYes


  • Berberine
  • Inflammation
  • Methotrexate
  • Oxidative stress

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • General Pharmacology, Toxicology and Pharmaceutics
  • Pharmacology (medical)


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