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Abstract
BackgroundRheumatoid arthritis (RA) is a chronic autoimmune disease. Soufeng sanjie formula (SF), which is composed of scolopendra (dried body of Scolopendra subspinipes mutilans L. Koch), scorpion (dried body of Buthus martensii Karsch), astragali radix (dried root of Astragalus membranaceus (Fisch.) Bge), and black soybean seed coats (seed coats of Glycine max (L.) Merr), is a traditional Chinese prescription for treating RA. However, the mechanism of SF in treating RA remains unclear. This study was aim to investigate the anti-arthritic effects of SF in a collagen-induced arthritis (CIA) mouse model and explore the mechanism by which SF alleviates arthritis in CIA mice.MethodsFor in vivo studies, female DBA/1J mice were used to establish the CIA model, and either SF (183 or 550 mg/kg/day) or methotrexate (MTX, 920 mg/kg, twice/week) was orally administered to the mice from the day of arthritis onset. After administration for 30 days, degree of ankle joint destruction and serum levels of IgG and inflammatory cytokines were determined. The balance of Th17/Treg cells in the spleen and lymph nodes was analyzed using flow cytometry. Moreover, the expression levels of retinoic acid receptor-related orphan nuclear receptor (ROR) γt and phosphorylated STAT3 (pSTAT3, Tyr705) in the spleen were detected by immunohistochemistry. Furthermore, the effect of SF on Th17 cells differentiation in vitro was investigated in CD4+ T cells under Th17 polarization conditions.ResultsSF decreased the arthritis score, ameliorated paw swelling, and reduced cartilage loss in the joint of CIA mice. In addition, SF decreased the levels of bovine collagen-specific IgG in sera of CIA mice. SF decreased the levels of inflammatory cytokines (TNF-α, IL-6, and IL-17A) and increased the level of IL-10 both in the sera and the joint of CIA mice. Moreover, SF treatment rebalanced the Th17/Treg ratio in the spleen and lymph nodes of CIA mice. SF also reduced the expression levels of ROR γt and pSTAT3 (Tyr705) in the spleen of CIA mice. In vitro, SF treatment reduced Th17 cell generation and IL-17A production and inhibited the expression of RORγt, IRF4, IL-17A, and pSTAT3 (Tyr705) under Th17 polarization conditions.ConclusionsOur results suggest that SF exhibits anti-arthritic effects and restores Th17/Treg homeostasis in CIA mice by inhibiting Th17 cell differentiation.
Highlights
Rheumatoid arthritis (RA) is a chronic autoimmune disease
enzyme-linked immunosorbent assay (ELISA) kits for tumor necrosis factor-α (TNF-α), IL-6, IL-17A, and IL-10 were purchased from R&D Systems (Minneapolis, MN, USA)
We demonstrated that sanjie formula (SF) had a significant therapeutic effect in a collagen-induced arthritis (CIA) mouse model, as evidenced by significantly decreased arthritis scores, joint swelling, and cartilage loss in CIA mice treated with SF compared with CIA vehicle mice
Summary
Rheumatoid arthritis (RA) is a chronic autoimmune disease. Koch), scorpion (dried body of Buthus martensii Karsch), astragali radix (dried root of Astragalus membranaceus (Fisch.) Bge), and black soybean seed coats (seed coats of Glycine max (L.) Merr), is a traditional Chinese prescription for treating RA. The mechanism of SF in treating RA remains unclear. Rheumatoid arthritis (RA) is a chronic autoimmune disease in which multiple immune cell types and signaling networks malfunction to elicit a maladaptive tissue repair process that leads to organ damage, predominantly in the. CD4+ T helper (Th) cells regulate immunity and inflammation through antigendependent activation and cytokine-dependent differentiation into functionally distinct effector and regulatory T cell subsets. The imbalance of regulatory T cells (Tregs) and Th17 cells can cause autoimmune diseases [8]. The inhibition of Th17 cell activity and IL-17 expression has become a potential therapeutic target for the treatment of RA
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