标题：Effects of berberine on human rheumatoid arthritis fibroblast-like synoviocytes.
作者：Wang XH;Jiang SM;Sun QW
作者机构：[Wang, X.-H] Department of Rheumatology, Qilu Hospital, Shandong University, Jinan 250012, China;[ Jiang, S.-M] State Key Laboratory of Genetic Engine 更多
通讯作者地址：[Jiang, SM]Fudan Univ, State Key Lab Genet Engn, Inst Genet, Sch Life Sci, Shanghai 200433, Peoples R China.
来源：Experimental Biology and Medicine: Journal of the Society for Experimental Biology and Medicine
关键词：berberine; rheumatoid arthritis; fibroblast-like synoviocyte;; proliferation; cell cycle; apoptosis
摘要：Activated rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs) play an important role in the initiation and progression of rheumatoid arthritis (RA). Rapid proliferation and defective apoptosis of RAFLSs are two main mechanisms contributing to synovial hyperplasia. Berberine, the major constituent of Coptidis Rhizoma, has been widely used as an antitumor and anti-inflammation agent. Here we show that berberine significantly inhibited cell proliferation of serum-starved human RAFLSs in a dose-dependent manner. Cell cycle analysis of berberine-treated RAFLSs indicated a cell cycle arrest at the G0/G1 phase. The inhibitory effects of berberine correlated with an induction of cyclin-dependent kinase (CDK) inhibitors Cip1/p21 and Kip1/p27 and a reduction of CDK2, CDK4 and CDK6, and cyclins D1, D2 and E. Furthermore, an apoptosis assay showed that berberine treatment increased apoptotic death of RAFLSs, which was associated with an increased expression of proapoptotic protein Bax and decreased expression of antiapoptotic proteins Bcl-2 and Bcl-xl, disruption of mitochondrial membrane potential, and activation of caspase-3, caspase-9 and poly (ADP-ribose) polymerase. Taken together, these results demonstrate that berberine exerts antiproliferative effects against RAFLSs, likely through deregulation of numerous cell cycle and apoptosis regulators, thus having potential therapeutic implications in the treatment of RA.