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A novel artemisinin derivative, 3-(12-beta-artemisininoxy) phenoxyl succinic acid (SM735), mediates immunosuppressive effects in vitro and in vivo.
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- Author(s): Zhou WL;Zhou WL; Wu JM; Wu QL; Wang JX; Zhou Y; Zhou R; He PL; Li XY; Yang YF; Zhang Y; Li Y; Zuo JP
- Source:
Acta pharmacologica Sinica [Acta Pharmacol Sin] 2005 Nov; Vol. 26 (11), pp. 1352-8.- Publication Type:
Journal Article; Research Support, Non-U.S. Gov't- Language:
English - Source:
- Additional Information
- Source: Publisher: Nature Publishing Group Country of Publication: United States NLM ID: 100956087 Publication Model: Print Cited Medium: Print ISSN: 1671-4083 (Print) Linking ISSN: 16714083 NLM ISO Abbreviation: Acta Pharmacol Sin Subsets: MEDLINE
- Publication Information: Publication: 2009- : New York : Nature Publishing Group
Original Publication: Beijing, China : Science Press, c2000- - Subject Terms: Artemisinins/*pharmacology ; Cytokines/*metabolism ; Hypersensitivity, Delayed/*prevention & control ; Immunosuppressive Agents/*pharmacology ; Succinates/*pharmacology; Animals ; Anti-Inflammatory Agents, Non-Steroidal/chemistry ; Artemisinins/administration & dosage ; Cell Proliferation/drug effects ; Cells, Cultured ; Dose-Response Relationship, Drug ; Hemolysis/drug effects ; Hypersensitivity, Delayed/chemically induced ; Immunosuppressive Agents/administration & dosage ; Inhibitory Concentration 50 ; Interferon-gamma/metabolism ; Interleukin-12/metabolism ; Lymphocyte Culture Test, Mixed ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Succinates/administration & dosage
- Abstract: 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 [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 IC(50) values of 0.33 micromol/L, 0.27 micromol/L, and 0.51 micromol/L, respectively. When compared with a CC(50) value of 53.1 micromol/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 on SM735. - Accession Number: 0 (3-(12-beta-artemisininoxy) phenoxyl succinic acid)
0 (Anti-Inflammatory Agents, Non-Steroidal)
0 (Artemisinins)
0 (Cytokines)
0 (Immunosuppressive Agents)
0 (Succinates)
187348-17-0 (Interleukin-12)
82115-62-6 (Interferon-gamma) - Publication Date: Date Created: 20051018 Date Completed: 20070509 Latest Revision: 20121115
- Publication Date: 20221213
- Accession Number: 10.1111/j.1745-7254.2005.00232.x
- Accession Number: 16225758
- Source:
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