Juglanin inhibits IL-1β-induced inflammation in human chondrocytes

Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):3614-3620. doi: 10.1080/21691401.2019.1657877.

Abstract

Osteoarthritis (OA) is one of the most characterized joint diseases associated with chondrocyte apoptosis. Juglanin has been reported to have anti-inflammation activity. This study aimed to evaluate the protective anti-inflammatory effects of juglanin in human OA chondrocytes. Human OA chondrocytes were pretreated with juglanin (10, 20 and 40 μM) for 2 h and subsequently stimulated with IL-1β for 24 h. Nitric oxide (NO) production was determined using the Griess method and prostaglandin E2 (PGE2), matrix metalloproteinase-3, -9 and -13 (MMP-3, MMP-9 and MMP-13), TNF-α, and IL-6 were assessed using ELISA. The expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), a disintegrin and metalloproteinase with thrombospondin motifs-4 and -5 (ADAMTS-4 and ADAMTS-5) were detected by qRT-PCR and western blot analysis. NF-κB signalling molecules were detected by western blot analysis. The results showed that juglanin dose-dependently suppressed PGE2, NO, MMP-1, MMP3, MMP13, TNF-α and IL-6 production induced by IL-1β. The expression of COX-2, iNOS, ADAMTS-4 and ADAMTS-5 induced by IL-1β were also suppressed by juglanin pretreatment. Western blot analysis showed that juglanin suppressed IL-1β-induced NF-κB activation. Taken together, we found that juglanin inhibits IL-1β-induced inflammation through the regulation of NF-κB signalling. Juglanin might be used as a therapeutic agent for treating OA.

Keywords: NF-κB; Osteoarthritis; anti-inflammation; chondrocytes; juglanin.

MeSH terms

  • ADAMTS4 Protein / genetics
  • ADAMTS4 Protein / metabolism
  • ADAMTS5 Protein / genetics
  • ADAMTS5 Protein / metabolism
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Cell Survival / drug effects
  • Chondrocytes / drug effects*
  • Chondrocytes / metabolism
  • Chondrocytes / pathology
  • Dinoprostone / biosynthesis
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation, Enzymologic / drug effects
  • Glycosides / pharmacology*
  • Glycosides / therapeutic use
  • Humans
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Inflammation / pathology
  • Interleukin-1beta / adverse effects*
  • Interleukin-6 / biosynthesis
  • Kaempferols / pharmacology*
  • Kaempferols / therapeutic use
  • Matrix Metalloproteinases / biosynthesis
  • NF-kappa B / metabolism
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Anti-Inflammatory Agents
  • Glycosides
  • Interleukin-1beta
  • Interleukin-6
  • Kaempferols
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • juglanin
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • ADAMTS5 Protein
  • Matrix Metalloproteinases
  • ADAMTS4 Protein
  • Dinoprostone