PloS one, 2013-06, Vol.8 (6), p.e66503
2013
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Isogarcinol is a new immunosuppressant
- Ist Teil von
- PloS one, 2013-06, Vol.8 (6), p.e66503
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2013
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0066503Titel-ID: cdi_plos_journals_1367545395
- Format
- –
- Schlagworte
- Acute toxicity, Allografts, Animals, Apoptosis, Autoimmune diseases, Biochemistry, Biological Products - administration & dosage, Biological Products - chemistry, Biological Products - pharmacology, Biological Products - toxicity, Biology, Biotechnology, Calcineurin, Calcineurin Inhibitors, Chemistry, Chinese medicine, Chromatography, Concanavalin A, Cyclosporin A, Cytotoxicity, Dosage and administration, Drug dosages, Drugs, Engineering, Enzyme Activation - drug effects, Enzymes, Ethanol, Garcinia, Garcinia mangostana, Gene expression, Graft rejection, Graft Survival - drug effects, Graft Survival - immunology, Hypersensitivity, Hypersensitivity (delayed), Hypersensitivity, Delayed - drug therapy, Hypersensitivity, Delayed - immunology, Immunology, Immunomodulation, Immunoregulation, Immunosuppression, Immunosuppressive agents, Immunosuppressive Agents - administration & dosage, Immunosuppressive Agents - chemistry, Immunosuppressive Agents - pharmacology, Immunosuppressive Agents - toxicity, Laboratories, Leukemia, Lymphocyte Activation - drug effects, Lymphocyte Activation - immunology, Lymphocyte Culture Test, Mixed, Lymphocytes, Lymphocytes T, Male, Medicine, Mice, Mitogens, Mixed leukocyte reaction, Molecular biology, Natural products, Oral administration, Pharmaceuticals, Phosphatases, Plant Extracts - administration & dosage, Plant Extracts - chemistry, Plant Extracts - pharmacology, Plant Extracts - toxicity, Protein phosphatase, Proteins, Rats, Signal transduction, Skin, Skin grafts, Skin Transplantation, Spleen, Staphylococcus infections, T-Lymphocytes - drug effects, T-Lymphocytes - immunology, Terpenes - administration & dosage, Terpenes - chemistry, Terpenes - pharmacology, Terpenes - toxicity, Toxicity, Tracheophyta - chemistry, Transplantation