Anhuienoside C Ameliorates Collagen-Induced Arthritis through Inhibition of MAPK and NF-κB Signaling Pathways.
Anhuienoside C Ameliorates Collagen-Induced Arthritis through Inhibition of MAPK and NF-κB Signaling Pathways.
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Anhuienoside C 通过抑制 MAPK 和 NF-kappa B 信号通路改善胶原诱导的关节炎
DOI：
10.3389/fphar.2017.00299
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发表时间：
2017
影响因子：
5.6
通讯作者：
Liu Z
中科院分区：
文献类型：
--
作者：
Liu Q;Xiao XH;Hu LB;Jie HY;Wang Y;Ye WC;Li MM;Liu Z
软叶银莲花（Anemone flaccida Fr.施密特）（毛茛科）（中国地乌）用于治疗拳伤和类风湿性关节炎（RA）。我们以前的报告表明，粗三萜皂苷从银莲花flaccida表现出抗关节炎的作用，对II型胶原诱导的关节炎大鼠。此外，还对从黄芪中分离得到的一种皂苷化合物安徽甙C（anhuienoside C，AC）进行了结构鉴定。在脂多糖（LPS）处理的巨噬细胞RAW 264.7细胞中，观察到flaccida抑制一氧化氮的产生。在这项研究中，我们研究了AC对预防和治疗胶原诱导的关节炎小鼠模型的影响，并评估了相关的潜在机制。我们观察到口服AC显著抑制足肿胀和关节炎评分，减少体重损失，并降低脾脏指数。疾病严重程度的改善伴随着踝关节中分化簇68（CD 68）阳性细胞的减少和关节滑膜中促炎细胞因子肿瘤坏死因子α（TNF-α）的抑制。机制研究表明，AC通过抑制LPS处理的RAW 264.7细胞中诱导型一氧化氮合酶、环氧合酶-2、TNF-α、白细胞介素（IL）-1β和IL-6的mRNA表达水平以及抑制炎性细胞因子如TNF-α、IL-1β和IL-6的产生来发挥其抗炎活性。AC还阻断LPS诱导的细胞外信号调节激酶、c-Jun N-末端激酶和p38丝裂原活化蛋白激酶途径的活化。此外，AC处理显著抑制LPS诱导的核因子κ B（NF-κB）活化，如通过下调TLR 4和抑制NF-κB p65的核转位以及通过活化和降解κ B抑制剂所示。这些结果表明，AC具有很大的潜力，被开发为人类RA的治疗剂。
Anemone flaccida Fr. Schmidt (Ranunculaceae) (Di Wu in Chinese) is used to treat punch injuries and rheumatoid arthritis (RA). Our previous report has shown that crude triterpenoid saponins from Anemone flaccida exhibited anti-arthritic effects on type II collagen-induced arthritis in rats. Furthermore, anhuienoside C (AC), a saponin compound isolated from A. flaccida, was observed to suppress the nitric oxide production in lipopolysaccharide (LPS)-treated macrophage RAW 264.7 cells. In this study, we examined the effects of AC on the prevention and treatment of collagen-induced arthritis in a mouse model and evaluated the potential mechanisms involved. We observed that oral administration of AC significantly suppressed the paw swelling and arthritic score, decreased the body weight loss, and decreased the spleen index. Improvement in the disease severity was accompanied by the reduction of cluster of differentiation 68 (CD68)-positive cells in the ankle joint and inhibition of the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α) in the synovium of the joint. Mechanistic studies indicated that AC exerted its anti-inflammatory activity by inhibiting the mRNA expression levels of inducible nitric oxide synthase, cyclooxygenase-2, TNF-α, interleukin (IL)-1β, and IL-6 and by suppressing the production of inflammatory cytokines such as TNF-α, IL-1β, and IL-6 in LPS-treated RAW 264.7 cells. AC also blocked the LPS-induced activation of the extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase pathways. Additionally, the LPS-induced activation of nuclear factor kappa-B (NF-κB) was significantly suppressed by AC treatment, as indicated by down-regulation of TLR4 and inhibition of the nuclear translocation of NF-κB p65 and by activation and degradation of the inhibitor of kappa B. These findings indicated that AC has a great potential to be developed as a therapeutic agent for human RA.