Department of Anatomy &Neurobiology, Northeast Ohio Medical University, 4209 St Rt 44, Rootstown, OH 44272, USA.
Sci Rep. 2017 Mar 3;7:43789. doi: 10.1038/srep43789.
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.
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。黄芩的根提取物（SBE）已被用于治疗炎症和其他疾病。在这里，我们对 SBE 进行了基于活性的 HPLC 分级，鉴定了活性成分，并研究了其软骨保护潜力。我们发现，含有黄岑素的 4 号馏分（F4）是最有效的馏分，因为它能够抑制 ROS 产生，并抑制包括 IL-6、COX-2、iNOS、MMP-3、MMP-9、MMP-13 和 ADAMTS-4 在内的分解代谢标志物的表达，这些标志物在 IL-1β 处理的 OA 软骨细胞中表达。在存在 IL-1β 的情况下，用 F4 处理的 OA 软骨细胞显示出显著增强的合成代谢基因 ACAN 和 COL2A1 的表达。在体外软骨降解模型中，F4 抑制了 IL-1β 处理的人软骨外植体中 s-GAG 的释放。F4 的抑制作用不是通过抑制 MAPKs 和 NF-κB 激活来介导的，而是通过在 OA 软骨细胞中在转录和转录后水平上抑制 c-Fos/AP-1 活性来介导的。纯化的黄岑素模拟了 F4 在 IL-1β 刺激的 OA 软骨细胞中的作用。我们的数据表明，SBE 中的黄岑素丰富馏分通过抑制病理条件下 OA 软骨细胞中的 c-Fos/AP-1 表达和活性来发挥软骨保护作用。
