1. [The synthesis and immunosuppressive effects of steroid-peptide linkers]
C Wang, S Peng, X Zhang, X Qiu Yao Xue Xue Bao. 1998;33(2):111-6.
Hydrocortisone was coupled with urotoxin tripeptide UTP-A, UTP-B and UTP-C respectively yielding 4 linkers. Their bioactivities such as prolongation of heterotopic transplanted cardiac tissue survival, inhibitory effects on phagocytosis of mouse peritoneal macrophages and the influence on Con A induced proliferation of spleen lymphocytes of mouse were observed. Compared with UTP-A, UTP-B, UTP-C or hydrocortisone the linkers were more potent immunosuppressants. The results suggest that the linker of steroid-peptide may simulate the permissive action.
2. [Immunosuppressive activity of exopolysaccharide from Paecilomyces gunnii]
Jianhui Xiao, Ning Fang, Yu Xiao, Ying Qi, Jinwei Liu, Zongqi Liang Zhong Yao Cai. 2004 Mar;27(3):192-5.
Objective: To investigate bioactivities of Paecilomyces gunnii exopolysaccharide (PGEP). Methods: The effects of PGEP on mice spleen lymphocytes proliferation, mice peritoneal macrophage (PMphi) phagocytosis and cytotoxin T lymphocytes (CTL) activity were studied by MTT method, neutral red colorimetry, respectively. Results: In vitro, mice spleen lymphocytes proliferation, mice peritoneal macrophage (PMphi) phagocytosis of neutral red and CTL activity were significant suppressed by PGEP, especially in 10 microg/ml. Conclusion: PGEP had the immunosuppressive activities.
3. (5R)-5-hydroxytriptolide (LLDT-8), a novel triptolide analog mediates immunosuppressive effects in vitro and in vivo
Ru Zhou, Fan Zhang, Pei-Lan He, Wen-Liang Zhou, Qing-Li Wu, Jian-Yi Xu, Yu Zhou, Wei Tang, Xiao-Yu Li, Yi-Fu Yang, Yuan-Chao Li, Jian-Ping Zuo Int Immunopharmacol. 2005 Dec;5(13-14):1895-903. doi: 10.1016/j.intimp.2005.06.009. Epub 2005 Jun 28.
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 microg/kg, i.p.; 40 microg/kg, p.o.) intensively suppressed 2,4-dinitrofluorobenzene (DNFB)-induced delayed type hypersensitivity (DTH) reactions. Treatment with LLDT-8 (40 microg/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.
