Byakangelicin inhibits IL-1β-induced mouse chondrocyte inflammation in vitro and ameliorates murine osteoarthritis in vivo

Int Immunopharmacol. 2020 Aug:85:106605. doi: 10.1016/j.intimp.2020.106605. Epub 2020 May 30.

Abstract

Osteoarthritis (OA) is a chronic musculoskeletal degeneration disease, resulting in severe consequences such as chronic pain and functional disability. Owing to the complex pathology, there are currently available preventative clinical therapies for OA. Several studies have reported the potential anti-inflammatory effects of byakangelicin (BYA), a component of the Angelica dahurica root extract; however, the effects of BYA in OA remain unknown. In this study, we investigated the protective effects of BYA in interleukin (IL)-1β-induced mouse chondrocytes in vitro and on surgical destabilization in a medial meniscus (DMM) mouse OA model in vivo. In vitro, BYA treatment inhibited IL-1β-mediated inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-alpha, and IL-6 expression. Moreover, BYA promoted the expression of type two collagen and aggrecan but inhibited the expression of thrombospondin motifs 5 and matrix metalloproteinases, leading to degradation of the extracellular matrix. In addition, BYA mechanistically suppressed nuclear factor-kappa B signaling in the IL-1β-induced chondrocytes. The protective effects of BYA in OA development were also observed in vivo using the DMM model. In conclusion, our results highlight BYA as a candidate for OA treatment and prevention.

Keywords: Byakangelicin; Chondrocyte; IL-1β; Inflammation; NF-κB; Osteoarthritis.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Cells, Cultured
  • Chondrocytes / drug effects
  • Cyclooxygenase 2 / immunology
  • Disease Models, Animal
  • Furocoumarins / pharmacology
  • Furocoumarins / therapeutic use*
  • Interleukin-1beta
  • Male
  • Mice, Inbred C57BL
  • Nitric Oxide Synthase Type II / immunology
  • Osteoarthritis / drug therapy*
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Anti-Inflammatory Agents
  • Furocoumarins
  • Interleukin-1beta
  • Tnf protein, mouse
  • Tumor Necrosis Factor-alpha
  • 9-(2,3-dihydroxy-3-methylbutoxy)-4-methoxy-7H-furo(3,2-g)(1)benzopyran-7-one
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2