Open AccessA novel artemisinin derivative, 3‐(12‐β‐artemisininoxy) phenoxyl succinic acid (SM735), mediates immunosuppressive effects in vitro and in vivo 1
Author(s) -
ZHOU Wenliang,
WU Jinming,
WU Qingli,
WANG Junxia,
ZHOU Yu,
ZHOU Ru,
HE Peilan,
LI Xiaoyu,
YANG Yifu,
ZHANG Yu,
LI Ying,
ZUO Jianping
Publication year - 2005
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2005.00232.x
Subject(s) - concanavalin a , splenocyte , ionomycin , pharmacology , in vivo , lipopolysaccharide , cytokine , proinflammatory cytokine , immune system , chemistry , in vitro , immunology , biochemistry , biology , inflammation , microbiology and biotechnology
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 [ 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 μmol/L, 0.27 μmol/L, and 0.51 μmol/L, respectively. When compared with a CC 50 value of 53.1 μmol/L, SM735 had a favorable safety range. SM735 dose‐dependently inhibited proinflammatory cytokine production [including interleukins (IL)‐12, interferon (IFN)‐γ and IL‐6] induced by LPS or PMA plus ionomycin. Upon ConA stimulation, SM735 suppressed IFN‐γ 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.