%0 Journal Article %T A novel artemisinin derivative, 3-(12-bold beta-artemisininoxy) phenoxyl succinic acid (SM735), mediates immunosuppressive effects in vitro and in vivo %A Zhou Wen-liang %A Wu Jin-ming %A Wu Qing-li %A Wang Jun-xia %A Zhou Yu %A Zhou Ru %A He Pei-lan %A Li Xiao-yu %A Yang Yi-fu %A Zhang Yu %A Li Ying %A Zuo Jian-ping %J Acta Pharmacologica Sinica %D 2016 %B 2016 %9 %! A novel artemisinin derivative, 3-(12-bold beta-artemisininoxy) phenoxyl succinic acid (SM735), mediates immunosuppressive effects in vitro and in vivo %K %X Aim: To study the immunosuppressive activity of SM735 {[3 -(12-beta-artemisininoxy)] phenoxyl succinic acid}, a synthetic artemisinin derivative with nonsteroidal anti-inflammatory drug structure, with the aim of finding potential immunosuppressive agents. Methods: Concanavalin A (ConA), lipopolysaccharide (LPS), and mixed lymphocyte reaction (MLR), were used to induce the proliferation of splenocytes, and [ 3 H]-thymidine incorporation was used to evaluate the proliferation of splenocytes. Cytokine production was promoted with ConA, LPS, or PMA plus ionomycin, and was detected with the enzyme-linked immunosorbent assay. Dinitrofluorobenzene (DNFB) and sheep red blood cells (SRBC) were used to induce delayed-type hypersensitivity and quantitative hemolysis of SRBC (QHS) mouse models, as criteria for the evaluation of in vivo immune activity. Results: SM735 strongly inhibited the proliferation of splenocytes induced by ConA, LPS, or MLR, with IC 50 values of 0.33 mumol/L, 0.27 mumol/L, and 0.51 mumol/L, respectively. When compared with a CC 50 value of 53.1 mumol/L, SM735 had a favorable safety range. SM735 dose-dependently inhibited proinflammatory cytokine production [including interleukins (IL)-12, interferon (IFN)-gamma and IL-6] induced by LPS or PMA plus ionomycin. Upon ConA stimulation, SM735 suppressed IFN-gamma in a dose-dependent manner, but did not affect IL-2 secretion. SM735 also strongly suppressed both T-cell-mediated delayed-type hypersensitivity (DTH) and B-cell-mediated QHS reactions. Conclusion: SM735 had strong immunosuppressive activity in vitro and in vivo , suggesting a potential role for SM735 as an immunosuppressive agent, and established the groundwork for further research onSM735. %U http://www.chinaphar.com/article/view/3932 %V 26 %N 11 %P 1352-1358 %@ 1745-7254