Protective Effects of Simvastatin and Hesperidin against Complete Freund's Adjuvant-Induced Rheumatoid Arthritis in Rats

Pharmacology. 2015;96(5-6):217-25. doi: 10.1159/000439538. Epub 2015 Sep 9.

Abstract

Background/aims: Rheumatoid arthritis (RA) is a disabling autoimmune disease for which most current treatments cause massive complications, thereby limiting treatment dose and duration. The anti-arthritic effects of the 3-hydroxy-3-metylglutary-CoA reductase inhibitor, simvastatin, and the natural flavonoid, hesperidin, were investigated against complete Freund's adjuvant-induced RA in rats.

Methods: A normal control group, an arthritis control group, 2 reference treatment groups receiving dexamethasone (1.5 mg/kg/day) and methotrexate (1 mg/kg/day), and 2 treatment groups receiving simvastatin (0.5 mg/kg/day) and hesperidin (200 mg/kg/day) were included in the study. Serum rheumatoid factor, matrix metalloprotinease-3 (MMP-3) and cartilage oligomeric matrix protein (COMP) as specific rheumatoid biomarkers, serum immunoglobulin G (IgG) and antinuclear antibody (ANA) as immunological biomarkers, serum tumor necrosis factor-alpha and interleukin-10 as immunomodulatory cytokines, serum myeloperoxidase (MPO) and C-reactive protein as inflammatory biomarkers, and malondialdehyde (MDA) and glutathione (GSH) as oxidative stress biomarkers were assessed, supported by joint and spleen histopathological study.

Results: Simvastatin significantly improved all the measured biomarkers, with MMP-3, COMP, and GSH restored to normal levels. Hesperidin significantly improved all the measured biomarkers, with COMP, IgG, ANA, MPO, MDA and GSH restored to normal levels.

Conclusion: Simvastatin and hesperidin may be promising protective agents against RA through immunomodulatory, anti-inflammatory and antioxidant potentials.

MeSH terms

  • Animals
  • Antirheumatic Agents / administration & dosage
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Experimental / immunology
  • Arthritis, Experimental / pathology
  • Arthritis, Experimental / prevention & control*
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / pathology
  • Arthritis, Rheumatoid / prevention & control*
  • Biomarkers / blood
  • Female
  • Freund's Adjuvant / immunology*
  • Hesperidin / administration & dosage
  • Hesperidin / therapeutic use*
  • Immunoglobulins / blood
  • Joints / drug effects
  • Joints / immunology
  • Joints / pathology
  • Rats, Wistar
  • Simvastatin / administration & dosage
  • Simvastatin / therapeutic use*
  • Spleen / drug effects
  • Spleen / pathology

Substances

  • Antirheumatic Agents
  • Biomarkers
  • Immunoglobulins
  • Freund's Adjuvant
  • Simvastatin
  • Hesperidin