A Modified Compound From Paeoniflorin, CP-25, Suppressed Immune Responses and Synovium Inflammation in Collagen-Induced Arthritis Mice

Abstract

Paeoniflorin-6’-O-benzene sulfonate (CP-25) is a modified paeoniflorin, which is the main bioactive component of total glucosides of peony. This study evaluated the anti-inflammatory and immunoregulatory effects of CP-25 in mice with collagen-induced arthritis (CIA) and the potential mechanisms underlying these effects. After the onset of CIA, mice were given CP-25 (17.5, 35, or 70 mg/kg) or methotrexate (MTX, 2.0 mg/kg). The arthritis index, swollen joint count, and joint and spleen histopathology were evaluated. T and B cell subsets were assayed using flow cytometry, while the proliferation of these cells and fibroblast-like synoviocytes (FLSs) were evaluated using the Cell Counting Kit-8. β2-adrenoceptor (β2-AR) expression was assayed using flow cytometry, immunohistochemistry, and western blotting. FLS migration and invasion were assayed using Transwells. CP-25 (35 or 70 mg/kg) attenuated the arthritis index and swollen joint count, alleviated joint and spleen histopathology, suppressed excessive T cell activation, and attenuated humoral immunity in CIA mice. CP-25 increased β2-AR expression on T cells, B cells, dendritic cells, and the synovium in CIA mice. CP-25 up-regulated the β2-AR agonist response and attenuated FLS activation; these effects may reflect CP-25-mediated reduction of β2-AR desensitization due to down-regulation of membrane G protein-coupled receptor kinase 2 expression. These results suggest that CP-25 suppressed immune responses and synovium inflammation in mice with CIA, effects that were associated with reduced β2-AR desensitization and the promotion of β2-AR signaling.

Regulation of T Cell Activities in Rheumatoid Arthritis by the Novel Fusion Protein IgD-Fc-Ig

“…IgD-Fc-Ig had no significant effect on anti-CD3/CD28 antibody-stimulated cells. Activated T cells, together with high expression of CD69 and CD154 (CD40L), play vital roles in RA-associated inflammation by producing inflammatory cytokines, which induce synovium inflammation and immune responses (33,34). We previously demonstrated that IgD increases the percentage of CD69 + and CD154 + cells, which might contribute to the elevated IgDR expression and Lck tyrosine phosphorylation (19).…”

GRK2 Mediated Abnormal Transduction of PGE2-EP4-cAMP-CREB Signaling Induces the Imbalance of Macrophages Polarization in Collagen-Induced Arthritis Mice

“…The final concentration of the reagent was 2 mg/mL. After overnight storage at 4 • C, 0.1 mL reagent was injected into the bottom of the tail of DBA/1 mice, and the same dose was injected into the back again after 21 days [17]. Mice were divided into normal group and CIA model group (n = 8 per group).…”

Analysis of Paeoniflorin Treatment of Cancer Based on Bioinformatic Network and Potential Target Prediction

“…3A,B).We found that most of genes were related to the response to immune, Cancer immunotherapy is a breakthrough in cancer, such as cytokine therapy [34]. previous articles have con rmed the in ammation and immunity of paeoni orin in diseases such as rheumatoid [38], allergic asthma [39] and arthritis [40]. In addition, the GO analysis results also explain that paeoni orin is also involved in cell migration [17,41], cell activation, and cell activity regulation.…”