Ononin ameliorates inflammation and cartilage degradation in rat chondrocytes with IL-1β-induced osteoarthritis by downregulating the MAPK and NF-κB pathways

BMC Complement Med Ther. 2022 Jan 27;22(1):25. doi: 10.1186/s12906-022-03504-5.

Abstract

Background: Osteoarthritis (OA) treatment aims to improve inflammation and delay cartilage degeneration. However, there is no effective strategy presently available. Ononin, a representative isoflavone glycoside component extracted from natural Chinese herbs, exerts anti-inflammatory and proliferative effects. However, the therapeutic effect of ononin on chondrocyte inflammation remains unclear.

Methods: In this study, we explored the therapeutic effect and potential mechanism of ononin in OA by establishing an interleukin-1 beta (IL-1β)-induced chondrocyte inflammation model.

Results: Our results verified that ononin alleviated the IL-1β-induced decrease in chondrocyte viability, attenuated the overexpression of the inflammatory factors tumour necrosis factor α (TNF-α) and interleukin 6 (IL-6), and simultaneously inhibited the expression of cartilage extracellular matrix (ECM)-degrading enzymes such as matrix metalloproteinase-13 (MMP-13). Furthermore, the decomposition of Collagen II protein could be alleviated in the OA model by ononin. Finally, ononin improved chondrocyte inflammation by downregulating the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) signalling pathways.

Conclusion: Our findings suggested that ononin could inhibit the IL-1β-induced proinflammatory response and ECM degradation in chondrocytes by interfering with the abnormal activation of the MAPK and NF-κB pathways, indicating its protective effect against OA.

Keywords: Chondrocyte; Collagen II; Inflammation; MAPK; MMP-13; NF-κB; Ononin; Osteoarthritis.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Cartilage / cytology
  • Cartilage / drug effects*
  • Cartilage / metabolism
  • Cartilage / pathology
  • Chondrocytes / drug effects
  • Chondrocytes / metabolism
  • Chondrocytes / pathology
  • Down-Regulation
  • Glucosides / pharmacology*
  • Glucosides / therapeutic use
  • Inflammation / drug therapy
  • Inflammation / metabolism*
  • Interleukin-1beta / metabolism*
  • Isoflavones / pharmacology*
  • Isoflavones / therapeutic use
  • MAP Kinase Signaling System
  • Male
  • Matrix Metalloproteinase 13 / metabolism
  • Mitogen-Activated Protein Kinases / metabolism*
  • NF-kappa B / metabolism*
  • Osteoarthritis* / drug therapy
  • Osteoarthritis* / metabolism
  • Osteoarthritis* / pathology
  • Phytotherapy
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Glucosides
  • Interleukin-1beta
  • Isoflavones
  • NF-kappa B
  • Plant Extracts
  • Tumor Necrosis Factor-alpha
  • calycosin-7-O-beta-D-glucoside
  • Mitogen-Activated Protein Kinases
  • Matrix Metalloproteinase 13