Abstract

Purpose: To explore the influence of the Miao medicine, Jinwujiangu decoction, on the interleukin (IL)- 17/IL-23 inflammatory axis of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA).Methods: Synovial tissue samples were randomly divided into a blank control group, high-dose (0.06mg/mL), medium-dose (0.6mg/mL), and low-dose (6.0mg/mL) groups of Jinwujiangu decoction, a leflunomide group, and a tripterygium glycosides group. Proliferation of RA synovial cells was detected by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. Enzyme-linked immunosorbent assay (ELISA) was used to determine the secretion of IL-6, transforming growth factor beta (TGF-β), and IL-17. Real-time polymerase chain reaction was used to evaluate the expression of IL-23R, IL-17R, RAR-related orphan receptor alpha (RORα), RORγt, and signal transducer and activator of transcription (STAT3) mRNA. The protein activities of IL-17R, STAT3 and pSTAT3 were assessed by Western blot assay.Results: Jinwujiangu decoction inhibited the proliferation of RA synovial cells. Treatment with different drug concentrations resulted in downregulation of IL-6, TGF-β, and IL-17 secretion. The expression levels of IL-23R, IL-17R, RORα, RORγt, and STAT3 mRNA in RA-FLS were significantly reduced after intervention with different drugs. Protein expression levels of STAT3, pSTAT3, and IL-17 in the different drug treatment groups were significantly decreased.Conclusion: Jinwujiangu decoction inhibits the secretion of IL-6 and TGF-β in RA-FLS, and intervenes to regulate gene expression of IL-23/IL-17 inflammation axis and suppress immune inflammation. The results of this study provide new evidence for the study of anti-inflammatory mechanism of TCM compound prescription.Keywords: Jinwujiangu decoction, IL-17/IL-23, Fibroblast-like synoviocytes, Rheumatoid arthritis, Ethnomedicine

Highlights

  • Rheumatoid arthritis (RA) is an autoimmune disease, in which inflammatory synovitis and synovial joint erosion is the main reason for bone destruction and joint deformity [1]

  • This study further investigated the effects of the Miao medicine, Jinwujiangu decoction, on the IL17/IL-23 axis in RA-Fibroblast-like synoviocytes (FLS), to explore the antiinflammatory effects of Jinwujiangu decoction on RA - FLS

  • This study found that Jinwujiangu decoction could up-regulate the expression of IL-23R, STAT3, PSTAT3RO, and RORγt in RA-FLS

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Summary

INTRODUCTION

Rheumatoid arthritis (RA) is an autoimmune disease, in which inflammatory synovitis and synovial joint erosion is the main reason for bone destruction and joint deformity [1]. The Miao medicine, Jinwujiangu decoction, has been used in the treatment of clinical experience of RA for a long time. It consists of Rhizoma cibotii, Periploca forrestii schltr, Caulis sinomenii, Homalomena occulta, Curcuma longa, Zaocys dhumnade, pseudo-ginseng, and licorice, with strong effects on kidney function, strengthening sinews, bone activation, expelling pathogenic wind, and tongluo. Previous studies showed that Jinwujiangu decoction could improve the clinical symptoms of joint pain and morning stiffness in RA patients [10]. It would reduce the protein activity of synovial cells and the secretion of IL17 and IL-23 in serum of CIA rats.

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