华中铁线莲 (Clematis pseudootophpra) 为湖北恩施地区习用草药，常见于祛风除湿、舒筋活络的复方，该植物的化学成分及药理活性研究尚未见报道。研究证实JAK-STAT 信号通路参与介导机体多种生理病理反应，在RA发生过程中具有决定性的作用。本项目前期实验结果表明华中铁线莲总膏及CP-1部位具有抗RA作用，且CP-1部位能在一定程度上抑制JAK和STAT 蛋白表达；对 CP-1进行初步分离得到12个化合物，其中有4个新化合物，均为比较少见的11, 13-二烯齐墩果烷型三萜。本项目基于JAK-STAT信号通路对RA滑膜增生和软骨侵蚀的调控作用，将细胞筛选、在体动物模型作用评价与分子靶点筛选相结合，确定华中铁线莲抗RA的物质基础，阐明其作用机制。该项目对从中草药中寻找选择性抑制JAK-STAT 信号通路的小分子天然抗RA药物具有十分重要的意义。

Clematis pseudootophpra has been used as an effective folk medicine for the treatment of rheumatoid arthritis (RA) in the Enshi of Hubei province. However, the effective substances and mechanism is unclear. Studies have shown that the JAK-STAT signaling pathway has a very close relationship with RA. The results of the preliminary experiments showed that alcohol extracts of C. pseudootophpra has significant anti-RA activity, and the CP-1 fraction was the active part. 12 compounds were isolated from the CP-1 fraction，including 4 new triterpenes, which belong to relatively rare 11, 13-diene oleanane type triterpenes. Preliminary research showed that CP-1 can inhibit the excess expression of STAT and JAK, which suggested that anti-RA activities of C. pseudootophpra is based on suppressing negative feed-back regulatory JAK-STAT signaling pathway. The project will study the material basis and action mechanism of C. pseudootophpra of anti-RA from a new approach, which may contribute a lot in discovering a new type of selective inhibitor of JAK-STAT signaling pathway from TCM to the treatment of RA.