Honokiol inhibits the progression of collagen-induced arthritis by reducing levels of pro-inflammatory cytokines and matrix metalloproteinases and blocking oxidative tissue damage

J Pharmacol Sci. 2010;114(1):69-78. doi: 10.1254/jphs.10070fp. Epub 2010 Aug 10.

Abstract

Plant-derived compounds with potent anti-inflammatory activity have attracted a great deal of attention as a source for novel anti-arthritic agents with minimal side effects. We attempted to determine the anti-arthritic effects of orally administered honokiol isolated from Magnolia species. The oral administration of honokiol inhibited the progression and severity of type II collagen (CII)-induced arthritis (CIA) by reducing clinical arthritis scores and paw swelling. The histological analysis demonstrated preserved joint space; and the immunohistochemical data showed that the levels of interleukin (IL)-17, matrix metalloproteinase (MMP)-3, MMP-9, MMP-13, and receptor activator for nuclear factor-κB ligand, as well as nitrotyrosine formation, were substantially suppressed in the honokiol-treated CIA mice. The elevated serum levels of tumor necrosis factor-α and IL-1β in the CIA mice were also restored to control levels via honokiol treatment. In the CIA mice, honokiol inhibited CII- or lipopolysaccharide-stimulated cytokine secretion in spleen cells, as well as CII-stimulated spleen cell proliferation. Furthermore, honokiol treatment reduced CIA-induced oxidative damage in the liver and kidney tissues of CIA mice. Collectively, the oral administration of honokiol inhibited CIA development by reducing the production of pro-inflammatory cytokines, MMP expressions, and oxidative stress. Thus, honokiol is an attractive candidate for an anti-arthritic agent.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental / metabolism
  • Arthritis, Experimental / pathology
  • Arthritis, Experimental / prevention & control*
  • Biphenyl Compounds / pharmacology
  • Biphenyl Compounds / therapeutic use*
  • Cattle
  • Cytokines / antagonists & inhibitors*
  • Cytokines / biosynthesis
  • Disease Progression*
  • Inflammation / metabolism
  • Inflammation / pathology
  • Inflammation / prevention & control
  • Inflammation Mediators / antagonists & inhibitors
  • Inflammation Mediators / metabolism
  • Inflammation Mediators / therapeutic use*
  • Lignans / pharmacology
  • Lignans / therapeutic use*
  • Male
  • Matrix Metalloproteinase Inhibitors*
  • Matrix Metalloproteinases / biosynthesis
  • Mice
  • Mice, Inbred DBA
  • Oxidation-Reduction / drug effects
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology

Substances

  • Biphenyl Compounds
  • Cytokines
  • Inflammation Mediators
  • Lignans
  • Matrix Metalloproteinase Inhibitors
  • honokiol
  • Matrix Metalloproteinases