Paeoniflorin-6'-O-benzene sulfonate (CP-25) is a new ester derivative of paeoniflorin with improved lipid solubility and oral bioavailability, as well as better anti-inflammatory activity than its parent compound. In this study we explored whether CP-25 exerted therapeutic effects in collagen-induced arthritis (CIA) mice through regulating B-cell activating factor (BAFF)-BAFF receptors-mediated signaling pathways. CIA mice were given CP-25 or injected with biological agents rituximab or etanercept for 40 days. In CIA mice, we found that T cells and B cells exhibited abnormal proliferation; the percentages of CD19+ total B cells, CD19+CD27+-activated B cells, CD19+BAFFR+ and CD19+TACI+ cells were significantly increased in PBMCs and spleen lymphocytes. CP-25 suppressed the indicators of arthritis, alleviated histopathology, accompanied by reduced BAFF and BAFF receptors expressions, inhibited serum immunoglobulin levels, decreased the B-cell subsets percentages, and prevented the expressions of key molecules in NF-κB signaling. Furthermore, we showed that treatment with CP-25 reduced CD19+TRAF2+ cell expressions stimulated by BAFF and decreased TRAF2 overexpression in HEK293 cells in vitro. Thus, CP-25 restored the abnormal T cells proliferation and B-cell percentages to the normal levels, and normalized the elevated levels of IgA, IgG2a and key proteins in NF-κB signaling. In comparison, rituximab and etanercept displayed stronger anti-inflammatory activities than CP-25; they suppressed the elevated inflammatory indexes to below the normal levels in CIA mice. In summary, our results provide evidence that CP-25 alleviates CIA and regulates the functions of B cells through BAFF-TRAF2-NF-κB signaling. CP-25 would be a soft immunomodulatory drug with anti-inflammatory effect.

中文翻译：

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eon药苷6'-O-苯磺酸盐通过下调BAFF-TRAF2-NF-κB信号传导减轻小鼠胶原性关节炎的发生：与生物制剂的比较。

eon药苷-6'-O-苯磺酸盐（CP-25）是pa药苷的新型酯衍生物，具有比其母体化合物更高的脂溶性和口服生物利用度，以及更好的抗炎活性。在这项研究中，我们探讨了CP-25是否通过调节B细胞活化因子（BAFF）-BAFF受体介导的信号通路在胶原诱导的关节炎（CIA）小鼠中发挥治疗作用。给CIA小鼠CP-25或注射利妥昔单抗或依那西普生物制剂40天。在CIA小鼠中，我们发现T细胞和B细胞表现出异常的增殖。PBMC和脾淋巴细胞中CD19 +总B细胞，CD19 + CD27 +活化B细胞，CD19 + BAFFR +和CD19 + TACI +细胞的百分比显着增加。CP-25抑制了关节炎指标，减轻了组织病理学，伴随着BAFF和BAFF受体表达的降低，抑制了血清免疫球蛋白的水平，降低了B细胞亚群的百分比，并阻止了NF-κB信号传导中关键分子的表达。此外，我们显示，用CP-25进行处理可降低BAFF刺激的CD19 + TRAF2 +细胞表达，并减少体外HEK293细胞中TRAF2的过度表达。因此，CP-25将异常的T细胞增殖和B细胞百分比恢复到正常水平，并使NF-κB信号传导中IgA，IgG2a和关键蛋白的升高水平正常化。相比之下，利妥昔单抗和依那西普显示出比CP-25更强的抗炎活性。他们将CIA小鼠的炎性指数升高抑制在正常水平以下。总之，我们的结果提供证据表明CP-25可通过BAFF-TRAF2-NF-κB信号传导减轻CIA并调节B细胞的功能。CP-25是一种具有抗炎作用的柔软免疫调节药物。