Immunosuppressive effects of demethylzeylasteral in a rat kidney transplantation model.
In this study, we examined the immunosuppressive activity of demethylzeylasteral (T-96), isolated from the traditional Chinese herbal medicine, Tripterygium wilfordii Hook f. Its immunosuppressive effect was investigated using mouse splenocytes in vitro, and in an in vivo rat kidney transplant model. T-96 inhibited mouse splenocyte proliferation in a dose dependent manner. In the rat kidney transplant study, rats were randomly divided into eight groups following kidney transplantation, and different doses of T-96 or cyclosporin A (CsA) were administered to each group. T-96 alone at doses of 10 or 20 mg/kg/day significantly prolonged the survival of kidney-transplanted rats, compared with transplanted but untreated control rats. A combination of T-96 and prednisone also significantly prolonged survival: 10 mg/kg/day T-96 with 10 mg/kg/day prednisone increased the survival time to 31.8+/-6.5 days. Moreover, the combination of T-96 and prednisone was also effective in suppressing rejection of rat transplanted kidneys. These results demonstrate the strong immunosuppressive activity of T-96 and suggest a possible clinical use for T-96 as an immunosuppressive agent in the fields of organ transplantation and autoimmune disorders.
Xu
Wenping
W
Department of Urology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, 200032 Shanghai, China.
Lin
Zongming
Z
Yang
Chunxin
C
Zhang
Yongkang
Y
Wang
Guomin
G
Xu
Xunhui
X
Lv
Qianzhou
Q
Ren
Yushen
Y
Dong
Ying
Y
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003208:Concanavalin A / Q000378:metabolism; D016572:Cyclosporine / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology*; D007165:Immunosuppression Therapy; D016030:Kidney Transplantation; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008516:Medicine, Chinese Traditional; D051379:Mice; D018517:Plant Roots; D011241:Prednisone / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D029757:Tripterygium; D014315:Triterpenes / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology
D014315:Triterpenes; C099855:demethylzeylasteral; D003208:Concanavalin A; D016572:Cyclosporine; D011241:Prednisone