Andrographolide Ameliorates Oxidative Stress, Inflammation and Histological Outcome in Complete Freund's Adjuvant-Induced Arthritis

Chem Biol Interact. 2020 Mar 1;319:108984. doi: 10.1016/j.cbi.2020.108984. Epub 2020 Feb 13.

Abstract

Objectives: As one of the main active ingredients of Chinese herbal medicine Andrographis paniculate, andrographolide is used in domestic clinical treatment for respiratory infections and inflammation. This study was designed to investigate the effects of andrographolide as an antioxidant on the level of oxidative stress, neutrophil accumulation and infiltration in joints and synovial tissue of arthritis rats induced by complete freund's adjuvant.

Methods: A rat model of rheumatoid arthritis was induced by subcutaneous injection of complete Freund's adjuvant in the footpad. The model was established 14 days after induction. The treatment was performed from 14th day to 35th day with different doses of andrographolide (25, 50, 100 mg/kg) and positive control methotrexate (3 mg/kg). The effects of andrographolide on oxidative stress, neutrophil accumulation and infiltration were measured by the paw swelling, arthritis score, the hot plate test, biochemical analysis, and histology.

Results: The medium and high-dose andrographolide (50, 100 mg/kg) group declined the levels of tumor necrosis factor-α, interleukin-6 and CXC chemokine ligand2, articular elastase and myeloperoxidase, and increased the levels of antioxidant enzymes superoxide dismutase, catalase, and glutathione. The activity of malondialdehyde and nitrite/nitrate in andrographolide (50, 100 mg/kg) group was weakened than the model group. The degree of swelling and arthritis score of andrographolide group was lower than the model group. The results of hot plate test showed that high dose of andrographolide significantly improved the anti-injury ability of rats; Radiological and histological results showed that the joint osteoporosis, inflammatory cell infiltration, synovial hyperplasia and other phenomena in the andrographolide group were significantly improved.

Conclusions: Andrographolide acts as a protective agent for the treatment of complete freund's adjuvant induced rheumatoid arthritis by inhibiting lipid peroxidation and nitrite/nitrate levels in a dose-dependent manner, enhancing antioxidant enzyme activity, reducing levels of chemokines and inflammatory factors, preventing neutrophil accumulation and infiltration.

Keywords: Andrographolide; Complete Freund's adjuvant; Inflammation; Oxidative stress.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Arthritis, Experimental / chemically induced*
  • Arthritis, Experimental / drug therapy*
  • Arthritis, Experimental / metabolism
  • Arthritis, Rheumatoid / chemically induced
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / metabolism
  • Catalase / metabolism
  • Disease Models, Animal
  • Diterpenes / pharmacology*
  • Edema / chemically induced
  • Edema / drug therapy
  • Edema / metabolism
  • Freund's Adjuvant / pharmacology*
  • Glutathione / metabolism
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Joints / drug effects
  • Joints / metabolism
  • Male
  • Methotrexate / metabolism
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Superoxide Dismutase / metabolism
  • Synovial Membrane / drug effects
  • Synovial Membrane / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antioxidants
  • Diterpenes
  • Interleukin-1beta
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • andrographolide
  • Freund's Adjuvant
  • Catalase
  • Superoxide Dismutase
  • Glutathione
  • Methotrexate