Wogonoside attenuates the articular cartilage injury and the infiltration of Th1/Th2-type cytokines in papain-induced osteoarthritis in rat model via inhibiting the NF-κB and ERK1/2 activation

Immunopharmacol Immunotoxicol. 2021 Jun;43(3):343-352. doi: 10.1080/08923973.2021.1913503. Epub 2021 Apr 21.

Abstract

Objects: Osteoarthritis is the most common joint disease and a major cause of functional limitation and pain in adults. This study aims to investigate the effect of wogonoside (WOG) on the progression of knee osteoarthritis (KOA) in model rats.

Materials and methods: Rats KOA models were established and treated with different doses of WOG (10 mg/kg, 20 mg/kg and 30 mg/kg). The degree of cartilage injury was detected by Mankin scores via HE/Alcian blue staining. The levels of IFN-γ and IL-4 in peripheral blood and synovial fluid and the Th1/Th2 ratio were detected by flow cytometry. The model mice were injected with NF-κB p65 or ERK1/2 inhibitors or activators to further investigate the effect of WOG on KOA.

Results: WOG significantly improved cartilage tissue damage and reduced the Mankins score. WOG down-regulated the level of IFN-γ while up-regulated the expression of IL-4, which maintained the balance of Th1/Th2 cells. Further studies showed that the expression of NF-κB p65, phosphorylated p65, cytoplasmic ERK1/2 and nuclear ERK1/2 were all inhibited by WOG. The results of reverse verification experiments showed that the activator of NF-κB p65 and ERK1/2 weakened the protective effect of WOG on KOA, and the inhibitor of NF-κB p65ERK1/2 enhanced the protective effect of WOG on KOA.

Conclusions: WOG inhibited the activation of NF-κB and ERK1/2 to alleviate the articular cartilage injury and Th1/th2 cytokine infiltration in KOA rats.

Keywords: ERK1/2; NF-κB; artilage injury; knee osteoarthritis; wogonoside.

Publication types

  • Video-Audio Media

MeSH terms

  • Animals
  • Cartilage, Articular / immunology*
  • Cartilage, Articular / pathology
  • Cytokines / immunology*
  • Disease Models, Animal
  • Flavanones / pharmacology*
  • Glucosides / pharmacology*
  • MAP Kinase Signaling System / drug effects*
  • MAP Kinase Signaling System / immunology
  • Male
  • Mitogen-Activated Protein Kinase 1 / immunology*
  • Mitogen-Activated Protein Kinase 3 / immunology*
  • NF-kappa B / immunology*
  • Osteoarthritis* / chemically induced
  • Osteoarthritis* / drug therapy
  • Osteoarthritis* / immunology
  • Papain / adverse effects*
  • Papain / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Th1 Cells / immunology*
  • Th1 Cells / pathology
  • Th2 Cells / immunology*
  • Th2 Cells / pathology

Substances

  • Cytokines
  • Flavanones
  • Glucosides
  • NF-kappa B
  • Mapk1 protein, rat
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Papain
  • wogonoside