Anti‑arthritic activity of Fu‑Fang‑Lu‑Jiao‑Shuang on collagen‑induced arthritis in Balb/c mice and its underlying mechanisms

Background: Rheumatoid arthritis (RA) is a common, autoimmune disorder characterized by progressive multiple joint destruction, deformity, disability and premature death in most patients. Fu‑Fang‑Lu‑Jiao‑Shuang (FFLJS) is an effective traditional Chinese medicine, which has long been used clinically to treat RA patients. Objective: The objective of this study is aimed to evaluate the anti‑rheumatic effects of FFLJS on collagen induced arthritis (CIA) model, as well as the underlying mechanisms, which have not previously been explored. Materials and Methods: CIA was induced by immunization with type II collagen (CII) in male Balb/c mice. The mice in the onset of arthritis were treated daily with FFLJS (125 or 500 mg/kg) or 1% carboxymethyl cellulose‑Na for 28 days. Paw thickness and arthritic score were evaluated to confirm the anti‑arthritic effect of FFLJS on CIA in mice. Levels of anti‑CII antibody, proinflammatory cytokines interleukin‑1 (IL‑1) β, IL‑17, and tumor necrosis factor‑α (TNF‑α) as well as prostaglandin E‑2 (PGE‑2) in serum and histological changes in the ankle joint were also analyzed. In addition, expressions of matrix metalloproteinases‑1 (MMP‑1), MMP‑3 and tissue inhibitors of matrix metalloproteases‑1 (TIMP‑1) in synovial tissue were also detected to further study the molecular mechanism of the anti‑arthritic effects of FFLJS. Results: During therapeutic treatment, FFLJS significantly reduced paw thickness and arthritic score in CIA mice, decreased the amounts of TNF‑α, IL‑1 β, IL‑17, PGE‑2 and anti‑CII antibody in serum. In addition, FFLJS treatment could prevent the bone destruction by reducing the expression of MMP‑1 and MMP‑3, increasing the expression of TIMP‑1 in synovial tissue of CIA mice. Conclusion: These findings offer the convincing evidence for the first time that the anti‑rheumatic effects of FFLJS might be related to down‑regulation of TNF‑α, IL‑1 β, IL‑17 and PGE‑2 levels for acute arthritis, and regulation of MMP‑1, MMP‑3 and TIMP‑1 protein expression for chronic arthritis.