Ginsenoside Compound K Ameliorates Osteoarthritis by Inhibiting the Chondrocyte Endoplasmic Reticulum Stress-Mediated IRE1α-TXNIP-NLRP3 Axis and Pyroptosis

J Agric Food Chem. 2023 Jan 25;71(3):1499-1509. doi: 10.1021/acs.jafc.2c06134. Epub 2023 Jan 11.


Osteoarthritis (OA) is a common joint disease, and studies have reported that the endoplasmic reticulum stress (ERS) in chondrocytes caused by the cartilage tissue damage could mediate the activation of Nod-like receptor protein 3 (NLRP3) inflammasomes through inositol-requiring enzyme 1 alpha (IRE1α) and thioredoxin interacting protein (TXNIP). Ginsenoside compound K (CK) has an inhibitory effect on IRE1α activation. However, the role of IRE1α-TXNIP and its interaction with CK are still unclear. In this study, we examined the role and mechanism of action of CK in OA. We found that CK ameliorated OA and ERS in IL-1β-treated chondrocytes and a monoiodoacetate-induced rat OA model. The effect of CK on inflammation, pyroptosis, and ERS was blocked by the ERS inducer tunicamycin. In conclusion, CK hindered OA progression by inhibiting the ERS-IRE1α-TXNIP-NLRP3 axis. Overall, our data indicate that CK could be useful in the treatment of OA and other chronic inflammatory diseases.

Keywords: TXNIP; compound K; endoplasmic reticulum stress; osteoarthritis.

MeSH terms

  • Animals
  • Apoptosis
  • Cell Cycle Proteins / metabolism
  • Cell Cycle Proteins / pharmacology
  • Chondrocytes
  • Endoplasmic Reticulum Stress
  • Endoribonucleases / genetics
  • Endoribonucleases / metabolism
  • Endoribonucleases / pharmacology
  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • NLR Proteins / metabolism
  • Osteoarthritis* / drug therapy
  • Osteoarthritis* / genetics
  • Osteoarthritis* / metabolism
  • Protein Serine-Threonine Kinases* / genetics
  • Protein Serine-Threonine Kinases* / metabolism
  • Pyroptosis
  • Rats


  • Protein Serine-Threonine Kinases
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • ginsenoside M1
  • NLR Proteins
  • Endoribonucleases
  • Inflammasomes
  • TXNIP protein, rat
  • Cell Cycle Proteins
  • Nlrp3 protein, rat