Curculigoside exerts significant anti‑arthritic effects in vivo and in vitro via regulation of the JAK/STAT/NF‑κB signaling pathway

Mol Med Rep. 2019 Mar;19(3):2057-2064. doi: 10.3892/mmr.2019.9854. Epub 2019 Jan 14.

Abstract

The present study aimed to investigate the anti‑arthritic effects of curculigoside isolated from the rhizome of Curculigo orchioides Gaertn in vivo and in vitro, as well as to determine the potential underlying mechanisms. A rat model of arthritis was induced with type II collagen. Arthritic rats were treated with curculigoside (50 mg/kg) and blood samples were collected to determine serum levels of tumor necrosis factor (TNF)‑α, interleukin (IL)‑1β, IL‑6, IL‑10, IL‑12 and IL‑17A. Furthermore, indices of the thymus and spleen were determined. The anti‑proliferative effects of curculigoside were detected with Cell Counting kit‑8 assays in rheumatoid arthritis‑derived fibroblast‑like synoviocyte MH7A cells. In addition, expression levels of Janus kinase (JAK)1, JAK3, signal transducer and activator of transcription (STAT)3, nuclear factor (NF)‑κB p65 and its inhibitor (IκB) were determined by western blotting. The results revealed that curculigoside inhibited paw swelling and arthritis scores in type II collagen‑induced arthritic (CIA) rats. Additionally, curculigoside decreased serum levels of TNF‑α, IL‑1β, IL‑6, IL‑10, IL‑12 and IL‑17A in CIA rats. Curculigoside also significantly inhibited MH7A cell proliferation in a time and concentration‑dependent manner. Furthermore, treatment downregulated the expression of JAK1, JAK3 and STAT3, and upregulated cytosolic nuclear factor (NF)‑κB p65 and IκB. In conclusion, the results of the present study indicated that curculigoside exhibited significant anti‑arthritic effects in vivo and in vitro, and the molecular mechanism may be associated with the JAK/STAT/NF‑κB signaling pathway.

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / chemically induced
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / pathology
  • Benzoates / administration & dosage*
  • Cell Proliferation / drug effects
  • Collagen Type II / toxicity
  • Disease Models, Animal
  • Gene Expression / drug effects
  • Glucosides / administration & dosage*
  • Humans
  • I-kappa B Proteins / genetics
  • Interleukins / genetics
  • Janus Kinase 1 / genetics*
  • Janus Kinase 3 / genetics*
  • Rats
  • STAT3 Transcription Factor / genetics*
  • Signal Transduction
  • Synoviocytes / drug effects
  • Transcription Factor RelA / genetics
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Benzoates
  • Collagen Type II
  • Glucosides
  • I-kappa B Proteins
  • Interleukins
  • Jak3 protein, rat
  • Rela protein, rat
  • STAT3 Transcription Factor
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • curculigoside
  • Jak1 protein, rat
  • Janus Kinase 1
  • Janus Kinase 3