title: Oridonin suppresses transplant rejection by depleting T cells from the periphery.
abstract: Oridonin is a natural compound purified from Rabdosia rubescens that has remarkable anti-inflammatory and antitumor activities. Although oridonin has been used in traditional Chinese medicine for many years to treat inflammatory diseases, the underlying mechanisms of these activities are not well understood. In this paper, we explored whether oridonin could be used in transplantation and the mechanisms of its immunosuppression. Oridonin efficacy in transplantation is manifested by prolonged graft survival and decreased graft infiltration. Oridonin induces T cell apoptosis in a concentration- and time-dependent manner. In vivo, oridonin depleted large numbers of T cells from the spleen and peripheral blood. Decreased T cell numbers resulted from apoptosis, which was accompanied by increased phagocyte numbers in the periphery. Reduction in the number of thymocytes was observed in mice treated for 8days, and CD4+CD8+ cells were more sensitive to apoptosis induced by oridonin. Additionally, successive treatment with oridonin for 16days resulted in a considerable reduction in the total number of spleen cells and spleen volume. Thus, T cell depletion may play an essential role in prolonged graft survival and immunosuppression induced by oridonin.
authors.affiliation: Key Laboratory of Hepatobiliary and Pancreatic Surgery & Digestive Organ Transplantation, The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, PR China.
authors.forename: Wenzhi
authors.initials: W
authors.lastname: Guo
authors.forename: Peiguo
authors.initials: P
authors.lastname: Zheng
authors.forename: Jiakai
authors.initials: J
authors.lastname: Zhang
authors.forename: Liang
authors.initials: L
authors.lastname: Ming
authors.forename: Chuang
authors.initials: C
authors.lastname: Zhou
authors.forename: Shuijun
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D045786:Diterpenes, Kaurane / Q000494:pharmacology / Q000627:therapeutic use*; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016038:Skin Transplantation; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D045786:Diterpenes, Kaurane; D007166:Immunosuppressive Agents; C011959:oridonin
keywords: Apoptosis; Graft rejection; Oridonin; Transplantation