Panaxynol induces fibroblast-like synovial cell apoptosis, inhibits proliferation and invasion through TLR4/NF-κB pathway to alleviate rheumatoid arthritis

Int Immunopharmacol. 2021 Dec;101(Pt A):108321. doi: 10.1016/j.intimp.2021.108321. Epub 2021 Nov 3.

Abstract

Background and purpose: Panaxynol (PAL, PubChem CID: 5281149) is a common natural minor component in Umbelliferae plants, such as Radix Saposhnikoviae Divaricatae. Modern pharmacology studies show that PAL has nutritional value and anti-inflammatory and other pharmaceutical activities. Therefore, the scientific hypothesis of PAL in the treatment of rheumatoid arthritis was put forward, and the hypothesis was further verified by Fibroblast-like synovial cells (RA-FLS) and Collagen Induced Arthritis (CIA) rats models.

Experimental method: CIA method was used to establish a rat arthritis model. After extracting RA-FLS, flow cytometry and immunofluorescence were used to explore the effect of PAL on the apoptosis and proliferation of RA-FLS. Wound healing and transwell experiment explored the effect of PAL on the migration and invasion of RA-FLS. Western blot analysis explored the inner mechanism of the effect of PAL on RA-FLS. At the same time, it also explored the role of PAL in CIA rats, including pathological section detection and western blot analysis.

Main results: PAL can promote the apoptosis and inhibit the proliferation, migration and invasion of RA-FLS. PAL can also reduce joint swelling in CIA rats, reduce pannus formation and inflammatory infiltration in the joints. Western blot analysis showed that PAL mainly played a role through the TLR4/NF-κB signaling pathway.

Conclusion: The results of in vivo and in vitro experiments show that PAL can effectively alleviate the condition of RA, and may be a potential drug for the treatment of RA.

Keywords: Collagen Induced Arthritis; Fibroblast-like synovial cells; Panaxynol; Rheumatoid arthritis; TLR4/NF-κB pathway.

MeSH terms

  • Animals
  • Antirheumatic Agents / therapeutic use*
  • Apoptosis / drug effects*
  • Arthritis, Rheumatoid / drug therapy*
  • Blotting, Western
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects*
  • Diynes / therapeutic use*
  • Fatty Alcohols / therapeutic use*
  • Female
  • NF-kappa B / metabolism*
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects*
  • Synovial Membrane / cytology*
  • Synovial Membrane / drug effects
  • Synovial Membrane / metabolism
  • Toll-Like Receptor 4 / metabolism*

Substances

  • Antirheumatic Agents
  • Diynes
  • Fatty Alcohols
  • NF-kappa B
  • Tlr4 protein, rat
  • Toll-Like Receptor 4
  • falcarinol