A wogonin-rich-fraction of Scutellaria baicalensis root extract exerts chondroprotective effects by suppressing IL-1β-induced activation of AP-1 in human OA chondrocytes.
A wogonin-rich-fraction of Scutellaria baicalensis root extract exerts chondroprotective effects by suppressing IL-1β-induced activation of AP-1 in human OA chondrocytes.
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DOI：
10.1038/srep43789
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发表时间：
2017-03-03
影响因子：
4.6
通讯作者：
Haqqi TM
中科院分区：
文献类型：
--
作者：
Khan NM;Haseeb A;Ansari MY;Haqqi TM
骨关节炎（OA）是一种常见的关节疾病，具有不同程度的炎症和持续的氧化应激。黄芩（Scutellaria baicalensis， SBE）的根提取物已被用于治疗炎症和其他疾病。在这里，我们对SBE进行了活性引导的高效液相色谱分离，鉴定了有效成分并研究了其保护软骨的潜力。我们发现含有Wogonin的部分-4 （F4）是最有效的部分，基于其抑制ROS生成和抑制IL-6、COX-2、iNOS、MMP-3、MMP-9、MMP-13和ADAMTS-4在il -1β处理的OA软骨细胞中的分解代谢标志物的能力。在IL-1β存在的情况下，F4处理的OA软骨细胞显示合成代谢基因ACAN和COL2A1的表达显著增强。在体外软骨降解模型中，F4抑制il -1β处理的人软骨外植体释放s-GAG。F4的抑制作用不是通过抑制MAPKs和NF-κB活化介导的，而是通过在OA软骨细胞的转录和转录后水平上抑制c-Fos/AP-1活性介导的。纯化的Wogonin模拟了F4在il -1β刺激的OA软骨细胞中的作用。我们的数据表明，在病理条件下，SBE中富含wogonin的部分通过抑制OA软骨细胞中c-Fos/AP-1的表达和活性来发挥软骨保护作用。
Osteoarthritis (OA) is a common joint disorder with varying degrees of inflammation and sustained oxidative stress. The root extract of Scutellaria baicalensis (SBE) has been used for the treatment of inflammatory and other diseases. Here, we performed activity-guided HPLC-fractionation of SBE, identified the active ingredient(s) and investigated its chondroprotective potential. We found that the Wogonin containing fraction-4 (F4) was the most potent fraction based on its ability to inhibit ROS production and the suppression of catabolic markers including IL-6, COX-2, iNOS, MMP-3, MMP-9, MMP-13 and ADAMTS-4 in IL-1β-treated OA chondrocytes. OA chondrocytes treated with F4 in the presence of IL-1β showed significantly enhanced expression of anabolic genes ACAN and COL2A1. In an in vitro model of cartilage degradation treatment with F4 inhibited s-GAG release from IL-1β-treated human cartilage explants. The inhibitory effect of F4 was not mediated through the inhibition of MAPKs and NF-κB activation but was mediated through the suppression of c-Fos/AP-1 activity at transcriptional and post transcriptional levels in OA chondrocytes. Purified Wogonin mimicked the effects of F4 in IL-1β-stimulated OA chondrocytes. Our data demonstrates that a Wogonin-rich fraction of SBE exert chondroprotective effects through the suppression of c-Fos/AP-1 expression and activity in OA chondrocytes under pathological conditions.