Peimine suppresses interleukin‑1β‑induced inflammation via MAPK downregulation in chondrocytes

Int J Mol Med. 2019 May;43(5):2241-2251. doi: 10.3892/ijmm.2019.4141. Epub 2019 Mar 21.

Abstract

Osteoarthritis (OA) is the most common type of degenerative joint disease and secreted inflammatory molecules serve a pivotal role in it. Peimine has been reported to have anti‑inflammatory activity. In order to investigate the potential therapeutic role of Peimine in OA, mouse articular chondrocytes were treated with IL‑1β and different doses of Peimine in vitro. The data revealed that Peimine not only suppressed IL‑1β‑induced production of nitric oxide (NO) and prostaglandin E2, but also reduced the protein levels of inducible NO synthase (iNOS) and cyclooxygenase‑2 (COX‑2). In addition, Peimine inhibited the IL‑1β‑induced mRNA expression of matrix metalloproteinase (MMP)‑1, MMP‑3, MMP‑9, MMP‑13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)‑4 and ADAMTS‑5. Furthermore, Peimine inhibited IL‑1β‑induced activation of the mitogen‑activated protein kinase (MAPK) pathway. The protective effect of Peimine on IL‑1β‑treated chondrocytes was attenuated following activation of the MAPK pathway, as demonstrated by the increased expression levels of MMP‑3, MMP‑13, ADAMTS‑5, iNOS and COX‑2 compared with the Peimine group. The in vivo data suggested that Peimine limited the development of OA in the mouse model. In general, the data indicate that Peimine suppresses IL‑1β‑induced inflammation in mouse chondrocytes by inhibiting the MAPK pathway, suggesting a promising therapeutic role for Peimine in the treatment of OA.

MeSH terms

  • ADAMTS Proteins / metabolism
  • Animals
  • Cartilage, Articular / drug effects
  • Cartilage, Articular / pathology
  • Cell Survival / drug effects
  • Cevanes / pharmacology
  • Cevanes / therapeutic use*
  • Chondrocytes / drug effects
  • Chondrocytes / enzymology*
  • Chondrocytes / pathology*
  • Cyclooxygenase 2 / metabolism
  • Dinoprostone / biosynthesis
  • Disease Models, Animal
  • Down-Regulation*
  • Enzyme Activation / drug effects
  • Inflammation / enzymology*
  • Inflammation / pathology
  • Interleukin-1beta
  • MAP Kinase Signaling System / drug effects
  • Matrix Metalloproteinases / metabolism
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinases / metabolism*
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase Type II / metabolism
  • Osteoarthritis / pathology

Substances

  • Cevanes
  • Interleukin-1beta
  • Nitric Oxide
  • verticine
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • Mitogen-Activated Protein Kinases
  • ADAMTS Proteins
  • Matrix Metalloproteinases
  • Dinoprostone