Chamazulene reverses osteoarthritic inflammation through regulation of matrix metalloproteinases (MMPs) and NF-kβ pathway in in-vitro and in-vivo models

Biosci Biotechnol Biochem. 2020 Feb;84(2):402-410. doi: 10.1080/09168451.2019.1682511. Epub 2019 Oct 23.

Abstract

This study was conducted to evaluate the protective effects of chamazulene against IL-1β-induced rat primary chondrocytes and complete Freund's adjuvant (CFA)-induced osteoarthritic inflammation in rats. Oxidative stress markers, pro-inflammatory cytokines, and regulatory proteins were measured. Chamazulene significantly reverted (p < 0.05) the levels of lipid peroxidation and enhanced the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) enzymes against IL-1β and CFA-induced oxidative stress. The levels of TNF-α and IL-6 were reduced (p < 0.05) in chamazulene treatment against IL-1β and CFA-induced inflammation. Western blot analysis results on the expressions of MMP-3, MMP-9, p65 NF-kβ, iNOS, and COX-2 showed chamazulene was able to protect the chondrocytes against IL-1β-induced osteoarthritic inflammation. Histopathology of rat hind ankle showed chamazulene significantly protected against CFA-induced osteoarthritic inflammation. Therefore, chamazulene can be recommended as a therapeutic agent for clinical trials against osteoarthritic inflammation.

Keywords: Inflammation; MMPs; chamazulene; oxidative stress; pro-inflammatory cytokines.

MeSH terms

  • Animals
  • Azulenes / therapeutic use*
  • Body Weight / drug effects
  • Cells, Cultured
  • Chondrocytes / drug effects
  • In Vitro Techniques
  • Interleukin-1beta / pharmacology
  • Male
  • Matrix Metalloproteinases / metabolism*
  • Models, Biological*
  • NF-kappa B / metabolism*
  • Osteoarthritis / enzymology
  • Osteoarthritis / metabolism
  • Osteoarthritis / pathology
  • Osteoarthritis / prevention & control*
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Azulenes
  • IL1B protein, rat
  • Interleukin-1beta
  • NF-kappa B
  • Matrix Metalloproteinases
  • chamazulene