title: Tamaractam, a New Bioactive Lactam from Tamarix ramosissima, Induces Apoptosis in Rheumatoid Arthritis Fibroblast-Like Synoviocytes.
abstract: Chemical investigation ofTamarix ramosissimaLedeb, a traditional herbal medicine used for rheumatoid arthritis (RA) treatment in northwest China, led to the discovery of a new phenolic aromatic rings substituted lactam, tamaractam (1), together with the previously reported compoundscis-N-feruloyl-3-O-methyldopamine (2) andtrans-N-feruloyl-3-O-methyldopamine (3). The structures of the compounds were determined by high resolution electrospray ionization mass spectroscopy (HRESIMS) and 1D and 2D-NMR experiments, as well as comparison with the literature data. The effects of the three compounds on the viability of RA fibroblast-like synoviocytes (RA-FLS) were assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Pro-apoptosis effect of compound1in RA-FLS was further investigated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay, activated caspase-3/7 level assessment using luminescence assay, and sub-G₁ fraction measurement using flow cytometry. It was found that these three compounds displayed variable proliferation inhibitory activity in RA-FLS, and compound1exhibited the strongest effect. Compound1could remarkably induce cellular apoptosis of RA-FLS, increase activated caspase-3/7 levels, and significantly increase sub-G₁ fraction in the cell cycle. The results suggested that compound1may inhibit the proliferation of RA-FLS through apoptosis-inducing effect, and these compounds may contribute to the anti-RA effect ofT. ramosissima.
authors.affiliation: School of Basic Medical Science, Ningxia Medical University, Yinchuan 750004, China. 15909511703@163.com.
authors.forename: Yao
authors.initials: Y
authors.lastname: Yao
authors.affiliation: School of Pharmacy, Ningxia Medical University, Yinchuan 750004, China. jiangcs1991@163.com.
authors.forename: Cheng-Shuai
authors.initials: CS
authors.lastname: Jiang
authors.affiliation: School of Pharmacy, Ningxia Medical University, Yinchuan 750004, China. sunna_2012@sina.com.
authors.forename: Na
authors.initials: N
authors.lastname: Sun
authors.affiliation: China National Center for Biotechnology Development, Beijing 100039, China. liwq1982@126.com.
authors.forename: Wei-Qi
authors.initials: WQ
authors.lastname: Li
authors.affiliation: School of Chinese Medicine, Ningxia Medical University, Yinchuan 750004, China. niuyangnxmu@sina.com.|Key Laboratory of Hui Medicine Modernization, Ministry of Education, Yinchuan 750004, China. niuyangnxmu@sina.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Niu
authors.affiliation: School of Basic Medical Science, Ningxia Medical University, Yinchuan 750004, China. hanhuaiqin76@sina.com.
authors.forename: Huai-Qin
authors.initials: HQ
authors.lastname: Han
authors.affiliation: School of Basic Medical Science, Ningxia Medical University, Yinchuan 750004, China. miaozhh@yahoo.com.
authors.forename: Zhen-Hua
authors.initials: ZH
authors.lastname: Miao
authors.affiliation: School of Basic Medical Science, Ningxia Medical University, Yinchuan 750004, China. zhaoxx@nxmu.edu.cn.
authors.forename: Xun-Xia
authors.initials: XX
authors.lastname: Zhao
authors.affiliation: Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, China. zhaojing1981@163.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: School of Pharmacy, Ningxia Medical University, Yinchuan 750004, China. asimov1983@sohu.com.|Ningxia Engineering and Technology Research Center for Modernization of Hui Medicine, Yinchuan 750004, China. asimov1983@sohu.com.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003846:Deoxyepinephrine / Q000031:analogs & derivatives / Q000737:chemistry* / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D007769:Lactams / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D008516:Medicine, Chinese Traditional; D000070918:Synoviocytes / Q000187:drug effects; D032363:Tamaricaceae / Q000737:chemistry
chemical_list: D007769:Lactams; D003846:Deoxyepinephrine
keywords: Tamarix ramosissima; apoptosis; fibroblast-like synoviocytes; growth inhibitory activity; rheumatoid arthritis; tamaractam