(5R)-5-hydroxytriptolide (LLDT-8), a novel triptolide analog mediates immunosuppressive effects in vitro and in vivo

doi:10.1016/j.intimp.2005.06.009

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	(5R)-5-hydroxytriptolide (LLDT-8), a novel triptolide analog mediates immunosuppressive effects in vitro and in vivo
	Zhou, R ; Zhang, F ; He, PL ; Zhou, WL ; Wu, QL ; Xu, JY ; Zhou, Y; Tang, W; Li, XY ; Yang, YF
刊名	INTERNATIONAL IMMUNOPHARMACOLOGY
	2005-12
卷号	5 期号:13-14 页码:1895-1903
关键词	(5R)-5-hydroxytriptolide immunosuppression
ISSN号	1567-5769
DOI	10.1016/j.intimp.2005.06.009
文献子类	Article
英文摘要	A series of triptolide analogs have been successfully synthesized. In the present study we demonstrated one of them, (5R)-5-hydroxytriptolide (LLDT-8), showed low cytotoxicity and relative high immunosuppressive activities as compared with its parent compound triptolide in vitro. The CC50 Values of triptolide and LLDT-8 were 2.1 +/- 0.3 and 256.6 +/- 73.8 nM, respectively. LLDT-8 significantly inhibited the proliferation of splenocytes induced by concanavalin A (ConA), lipopolysaccharide (LPS), or mixed lymphocyte reaction (MLR), and the IC50 values were 131.7 +/- 32.4, 171.5 +/- 17.3, and 38.8 +/- 5.1 nM, respectively. LLDT-8 (25, 50, 100 nM) dose-dependently reduced the production of Th1 type cytokines (IFN-gamma, IL-2) and inflammatory cytokines (TNF-alpha, IL-6) in vitro. Administration of LLDT-8 (at the low dose of 0.4 mu g/kg, i.p.; 40 mu g/kg, p.o.) intensively suppressed 2,4-dinitrofluorobenzene (DNFB)-induced delayed type hypersensitivity (DTH) reactions. Treatment with LLDT-8 (40 mu g/kg, i.p. and p.o.) also markedly inhibited the sheep red blood cell (SRBC)-induced antibody production in BLAB/c mice. Most importantly, comparing with triptolide, LLDT-8 significantly reduced toxicity, with a 122-fold lower cytotoxicity in vitro and 10-fold lower acute toxicity in vivo. The results suggested that LLDT-8 had immunosuppressive activities in both cellular and humoral immune responses. LLDT-8 might be a potential therapeutic agent for immune-related diseases. (c) 2005 Published by Elsevier B.V.
WOS关键词	TRIPTERYGIUM-WILFORDII HOOK ; DELAYED-TYPE HYPERSENSITIVITY ; COLLAGEN-INDUCED ARTHRITIS ; MESSENGER-RNA EXPRESSION ; CHINESE HERBAL REMEDY ; T-CELLS ; CYTOKINES ; INHIBITION ; EXTRACT ; SURVIVAL
WOS研究方向	Immunology ; Pharmacology & Pharmacy
语种	英语
出版者	ELSEVIER SCIENCE BV
WOS记录号	WOS:000233686600012
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/273762]
专题	药理学第一研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Zuo, JP
作者单位	1.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, Grad Sch,Lab Immunopharmacol,State Key Lab Drug R, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, Grad Sch,Lab Cheml,State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Zhou, R,Zhang, F,He, PL,et al. (5R)-5-hydroxytriptolide (LLDT-8), a novel triptolide analog mediates immunosuppressive effects in vitro and in vivo[J]. INTERNATIONAL IMMUNOPHARMACOLOGY,2005,5(13-14):1895-1903.
APA	Zhou, R.,Zhang, F.,He, PL.,Zhou, WL.,Wu, QL.,...&Zuo, JP.(2005).(5R)-5-hydroxytriptolide (LLDT-8), a novel triptolide analog mediates immunosuppressive effects in vitro and in vivo.INTERNATIONAL IMMUNOPHARMACOLOGY,5(13-14),1895-1903.
MLA	Zhou, R,et al."(5R)-5-hydroxytriptolide (LLDT-8), a novel triptolide analog mediates immunosuppressive effects in vitro and in vivo".INTERNATIONAL IMMUNOPHARMACOLOGY 5.13-14(2005):1895-1903.