Triterpenoid Saponin W3 from Anemone flaccida Suppresses Osteoclast Differentiation through Inhibiting Activation of MAPKs and NF-κB Pathways.
Triterpenoid Saponin W3 from Anemone flaccida Suppresses Osteoclast Differentiation through Inhibiting Activation of MAPKs and NF-κB Pathways.
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DOI：
10.7150/ijbs.12296
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发表时间：
2015
影响因子：
9.2
通讯作者：
Lin N
中科院分区：
文献类型：
--
作者：
Kong X;Yang Y;Wu W;Wan H;Li X;Zhong M;Su X;Jia S;Lin N
炎症关节内破骨细胞的过度骨吸收是类风湿关节炎最特殊的标志。黄花蒿在中国民间医学中用于治疗关节炎由来已久；然而，黄花蒿抗关节炎作用的有效成分仍然是难以捉摸的。本研究利用核因子κ b配体受体激活剂（receptor activator of nuclear factor κ b ligand， RANKL）诱导的破骨细胞形成模型，鉴定了从黄花楸提取物中分离得到的皂苷W3为其主要活性成分。W3剂量依赖性地抑制肌动蛋白环的形成和腔隙吸收。机制研究表明，W3抑制rankl诱导的TRAF6表达，降低丝裂原活化蛋白激酶（MAPKs）和i -κB -α磷酸化，抑制NF-κB p65 DNA结合活性。此外，W3几乎消除了活化T细胞c-Fos和核因子（NFATc1）的表达。因此，我们的研究结果表明，尽管需要进一步的体内和临床试验评估，但W3是治疗溶解性骨病的潜在药物。
Excessive bone resorption by osteoclasts within inflamed joints is the most specific hallmark of rheumatoid arthritis. A. flaccida has long been used for the treatment of arthritis in folk medicine of China; however, the active ingredients responsible for the anti-arthritis effects of A. flaccida are still elusive. In this study, W3, a saponin isolated from the extract of A. flaccida was identified as the major active ingredient by using an osteoclast formation model induced by receptor activator of nuclear factor kappa-B ligand (RANKL). W3 dose-dependently suppressed the actin ring formation and lacunar resorption. Mechanistic investigation revealed that W3 inhibited the RANKL-induced TRAF6 expression, decreased phosphorylation of mitogen-activated protein kinases (MAPKs) and IκB-α, and suppressed NF-κB p65 DNA binding activity. Furthermore, W3 almost abrogated the expression of c-Fos and nuclear factor of activated T cells (NFATc1). Therefore, our results suggest that W3 is a potential agent for treating lytic bone diseases although further evaluation in vivo and in clinical trials is needed.