Schisandrae Fructus Inhibits IL-1β-Induced Matrix Metalloproteinases and Inflammatory Mediators Production in SW1353 Human Chondrocytes by Suppressing NF-κB and MAPK Activation

Drug Dev Res. 2015 Dec;76(8):474-83. doi: 10.1002/ddr.21283. Epub 2015 Oct 7.

Abstract

Proinflammatory cytokine interleukin-1 beta (IL-1β) plays a crucial role in the pathogenesis of osteoarthritis (OA) by stimulating several mediators that contribute to cartilage degradation. Schisandrae Fructus (SF), the dried fruit of Schisandra chinensis (Turcz.) Baill. (Magnoliaceae), is widely used in traditional medicine for the treatment of a number of chronic inflammatory diseases. This study investigated the antiosteoarthritis properties of an ethanol extract of SF on IL-1β-stimulated SW1353 chondrocytes. SF attenuated IL-1β-induced expression and activity of matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 and also reduced the elevated levels of cyclooxygenase-2 and inducible nitric oxide synthase associated with the inhibition of prostaglandin E2 and nitric oxide production in IL-1β-stimulated SW1353 chondrocytes. In addition, SF markedly suppressed the nuclear translocation of nuclear factor-kappa B (NF-κB) by blocking inhibitor κB-alpha degradation and inhibited the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK). These results indicate that the inhibitory effect of SF on IL-1β-stimulated expression of MMPs and inflammatory mediators production in SW1353 cells were associated with the suppression of the NF-κB and JNK/p38 MAPK signaling pathways. The results from this study indicate that SF may have therapeutic potential for the treatment of OA due to its anti-inflammatory and chondroprotective features.

Keywords: NF-κB; Schisandra chinensis; matrix metalloproteinase; mitogen-activated protein kinases; osteoarthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Chondrocytes / drug effects*
  • Chondrocytes / immunology
  • Chondrocytes / metabolism
  • Cyclooxygenase 2 / metabolism
  • Dinoprostone / metabolism
  • Drug Interactions
  • Enzyme Induction / drug effects
  • Fruit / chemistry
  • Humans
  • Inflammation Mediators / antagonists & inhibitors
  • Interleukin-1beta / antagonists & inhibitors*
  • Interleukin-1beta / pharmacology
  • MAP Kinase Signaling System / drug effects
  • Matrix Metalloproteinases / biosynthesis*
  • Matrix Metalloproteinases / metabolism
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Osteoarthritis / drug therapy
  • Phosphorylation / drug effects
  • Plant Extracts / pharmacology*
  • Schisandra / chemistry*

Substances

  • Inflammation Mediators
  • Interleukin-1beta
  • NF-kappa B
  • Plant Extracts
  • Nitric Oxide
  • NOS2 protein, human
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Mitogen-Activated Protein Kinases
  • Matrix Metalloproteinases
  • Dinoprostone