title: Isogarcinol is a new immunosuppressant.
abstract: Calcineurin (CN), a unique protein phosphatase, plays an important role in immune regulation. In this study we used CN as a target enzyme to investigate the immunosuppressive properties of a series of natural compounds from Garcinia mangostana L., and discovered an active compound, isogarcinol. Enzymatic assays showed that isogarcinol inhibited CN in a dose-dependent manner. At concentrations resulting in relatively low cytotoxicity isogarcinol significantly inhibited proliferation of murine spleen T-lymphocytes induced by concanavalin A (ConA) and the mixed lymphocyte reaction (MLR). In addition, it performed much better in acute toxicity tests and via oral administration in mice than cyclosporin A (CsA), with few adverse reactions and low toxicity in experimental animals. Oral administration of isogarcinol in mice resulted in a dose-dependent decrease in delayed type hypersensitivity (DTH) and prolonged graft survival in allogeneic skin transplantation. These findings suggest that isogarcinol could serve as a new oral immunomodulatory drug for preventing transplant rejection, and for long-term medication in autoimmune diseases.
authors.affiliation: Department of Biochemistry and Molecular Biology, Beijing Normal University, Gene Engineering and Biotechnology Beijing Key Laboratory, Beijing, PR of China.
authors.forename: Juren
authors.initials: J
authors.lastname: Cen
authors.forename: Mingshu
authors.initials: M
authors.lastname: Shi
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Yang
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Fu
authors.forename: Hailing
authors.initials: H
authors.lastname: Zhou
authors.forename: Mengqi
authors.initials: M
authors.lastname: Wang
authors.forename: Zhenyi
authors.initials: Z
authors.lastname: Su
authors.forename: Qun
authors.initials: Q
authors.lastname: Wei
mesh_terms: D064591:Allografts; D000818:Animals; D001688:Biological Products / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D065095:Calcineurin Inhibitors; D004789:Enzyme Activation / Q000187:drug effects; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000188:drug therapy / Q000276:immunology; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D016038:Skin Transplantation; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013729:Terpenes / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D064028:Tracheophyta / Q000737:chemistry*
chemical_list: D001688:Biological Products; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D010936:Plant Extracts; D013729:Terpenes; C000617954:isogarcinol