Synergistic activity of curcumin with methotrexate in ameliorating Freund's Complete Adjuvant induced arthritis with reduced hepatotoxicity in experimental animals

Eur J Pharmacol. 2011 Oct 1;668(1-2):293-8. doi: 10.1016/j.ejphar.2011.06.006. Epub 2011 Jun 16.


Methotrexate is employed in low doses for the treatment of rheumatoid arthritis. One of the major drawbacks with methotrexate is hepatotoxicity resulting in poor compliance of therapy. Curcumin is an extensively used spice possessing both anti-arthritic and hepatoprotective potential. The present study was aimed at investigating the effect of curcumin (30 and 100 mg/kg) in combination with subtherapeutic dose of methotrexate (1 mg/kg) is salvaging hepatotoxicity, oxidative stress and producing synergistic anti-arthritic action with methotrexate. Wistar albino rats were induced with arthritis by subplantar injection of Freund's Complete Adjuvant and pronounced arthritis was seen after 9 days of injection. Groups of animals were treated with subtherapeutic dose of methotrexate followed half an hour later with 30 and 100mg/kg of curcumin from day 9 up to days 45 by intraperitoneal route. Methotrexate treatment in Freund's Complete Adjuvant induced arthritic animals produced elevation in the levels of aminotransferases, alkaline phosphatase, total and direct bilirubin. Enhanced oxidative stress in terms of measured lipid peroxides was observed in the methotrexate treated group. Curcumin significantly circumvented hepatotoxicity induced by methotrexate as evidenced by a change in biochemical markers possibly due to its strong anti-oxidant action. Hepatoprotective potential of curcumin was also confirmed from histological evaluation. Sub-therapeutic dose of methotrexate elicited substantial anti-arthritic action when used in combination with curcumin implying that the latter potentiated its action. Concomitant administration of curcumin with methotrexate was also found to minimize liver damage.

MeSH terms

  • Alanine Transaminase / blood
  • Alkaline Phosphatase / blood
  • Animals
  • Arthritis, Experimental / chemically induced
  • Arthritis, Experimental / drug therapy*
  • Arthritis, Experimental / metabolism
  • Arthritis, Experimental / pathology
  • Aspartate Aminotransferases / blood
  • Bilirubin / metabolism
  • Curcumin / adverse effects*
  • Curcumin / pharmacology*
  • Curcumin / therapeutic use
  • Cytoprotection / drug effects
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Female
  • Freund's Adjuvant / adverse effects*
  • Lipid Peroxidation / drug effects
  • Liver / drug effects*
  • Liver / pathology
  • Methotrexate / adverse effects*
  • Methotrexate / pharmacology*
  • Methotrexate / therapeutic use
  • Organ Size / drug effects
  • Rats
  • Rats, Wistar


  • Freund's Adjuvant
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Alkaline Phosphatase
  • Curcumin
  • Bilirubin
  • Methotrexate