Tetrandrine Represses Inflammation and Attenuates Osteoarthritis by Selective Inhibition of COX-2  

作　　者：Ping GAO Zhi-wei RAO Min LI Xu-ying SUN Qian-yan GAO Tian-ze SHANG Chao CHEN Cheng-liang ZHANG 

机构地区：[1]Department of Pharmacy,Wuhan Children's Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430016,China [2]Department of Pharmacy,Central Hospital of Xianning,the First Affliate Hospital of Hubei University of Science and Technology,Xianning 437100,China [3]Department of Pharmacy,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China [4]Department of Orthopedics,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China

出　　处：《Current Medical Science》2023年第3期505-513,共9页当代医学科学（英文）

基　　金：This study was supported by the Natural Science Foundation of Hubei Province(No.2020CFB868).

摘　　要：Objective There is a lack of effective and long-term safe drugs for the treatment of osteoarthritis(OA).Tetrandrine(Tet)has been approved and used to treat rheumatoid arthritis for several decades,but its effect on OA has not been investigated.Herein,we explored the effect of Tet on OA and its underlying mechanism.Methods OA was induced using destabilization of the medial meniscus(DMM)in C57BL/6J mice.The animals were randomly divided into sham,DMM,Tet,celecoxib(CXB),and indomethacin(INDO)groups.Each group was given solvent or corresponding drugs by gavage for 7 weeks after convalescence.Pathological staining,OARSI scores,micro-computed tomography and behavior tests were performed to evaluate the effects of Tet.Results Tet remarkably alleviated cartilage injury in the knee joint,limited bone remodeling in the subchondral bone,and delayed progression of OA.Tet also significantly relieved joint pain and maintained function.Further mechanistic studies revealed that Tet lowered inflammatory cytokine levels and selectively suppressed gene and protein expression of cyclooxygenase(COX)-2 but not COX-1(P<0.01).Tet also reduced the production of prostaglandin E2 without damaging the gastric mucosa.Conclusion We found that Tet could selectively inhibit COX-2 gene expression and decrease cytokine levels in mice,thus reducing inflammation and improving OA without obvious gastric adverse events.These results provide a scientific basis for the clinical application of Tet in the treatment of OA.

关 键 词：TETRANDRINE OSTEOARTHRITIS CYCLOOXYGENASE-2 gastric mucosa 

分 类 号：R684.3[医药卫生—骨科学]