A novel artemisinin derivative, 3-(12-β-artemisininoxy) phenoxyl succinic acid (SM735), mediates immunosuppressive effects in vitro and in vivo  

作　　者：Wen-liang ZHOU Jin-ming WU Qing-li WU Jun-xia WANG Yu ZHOU Ru ZHOU Pei-lan HE Xiao-yu LI Yi-fu YANG Yu ZHANG Ying LI Jian-ping ZUO 

机构地区：[1]Laboratories of Immunopharmacology [2]Laboratories of Synthetic Chemistry, Graduate School of the Chinese Academy of Sciences, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China

出　　处：《Acta Pharmacologica Sinica》2005年第11期1352-1358,共7页中国药理学报（英文版）

基　　金：Project supported by the Knowledge Innovation Program of the Chinese Academy of Sciences (№ KSCX2-SW-202).

摘　　要：Aim： To study the immunosuppressive activity of SM735 {[3-（12-β-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 [^3H]-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 IC50 values of 0.33 μmol/L, 0.27 μmol/L, and 0.51 μmol/L, respectively. When compared with a CC50 value of 53.1 μmol/L, SM735 had a favorable safety range. SM735 dose-dependently inhibited proinflarnmatory cytokine production [including interleukins （IL）-12, interferon （IFN）-y and IL-6] induced by LPS or PMA plus ionomycin. Upon ConA stimulation, SM735 suppressed IFN-y 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 on SM735.Aim： To study the immunosuppressive activity of SM735 {[3-（12-β-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 [^3H]-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 IC50 values of 0.33 μmol/L, 0.27 μmol/L, and 0.51 μmol/L, respectively. When compared with a CC50 value of 53.1 μmol/L, SM735 had a favorable safety range. SM735 dose-dependently inhibited proinflarnmatory cytokine production [including interleukins （IL）-12, interferon （IFN）-y and IL-6] induced by LPS or PMA plus ionomycin. Upon ConA stimulation, SM735 suppressed IFN-y 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 on SM735.

关 键 词：ARTEMISININ non-steroidal anti-inflammatory agents SM735 immuno-suppressive activity 

分 类 号：R979.5[医药卫生—药品]