phenanthrenes and Weight-Gain

Triptolide (TPT) is a diterpenoid triepoxide extracted from the Chinese herb Tripterygium wilfordii Hook. F. It exhibits potent immunosuppressive and anti-inflammatory properties. This study was undertaken to investigate its effects on prolongation of islet allograft survival in rodents. Additionally, we investigated whether TPT would be toxic to islet function in vivo.. We transplanted BALB/c islets to either chemically induced diabetic C57BL/6 mice or spontaneously diabetic nonobese diabetic (NOD) mice. TPT was injected within 2 weeks or continuously, until rejection, in the two combinations. Then, we evaluated the toxicity of TPT on islet function by daily injection to naive BALB/c or diabetic BALB/c that was cured by syngeneic islet transplantation under the kidney capsule. Mice injected with cyclosporine A (CsA) or vehicle served as controls. Intraperitoneal glucose tolerance tests (IPGTTs) performed at 4 and 8 weeks in the naive BALB/c group, and at 2, 4, 6, and 8 weeks in the syngeneic transplanted group.. The medium survival time of islets allograft from TPT treated C57BL/6 and NOD recipients were 28.5 days (range 24-30 days, n=10) and 33.0 days (range 15-47 days, n=6), respectively, and they were significantly different from those of the vehicle treated controls, which were 14.0 days (range 13-16 days, n=6) and 5.0 days (range 4-10 days, n=6), respectively (all P<0.0001). The IPGTT demonstrated that there was no difference between the TPT treated and vehicle treated groups, either in the normal or syngeneic transplanted islet BALB/c mice. However, CsA injection impaired islet function in both normal and syngeneic transplanted mice as early as 4 weeks.. TPT prolonged islets allograft survival in a chemically induced diabetic or an autoimmune diabetic murine model without impairment of islet function.

Topics: Animals; Blood Glucose; Cyclosporine; Diabetes Mellitus; Diabetes Mellitus, Experimental; Disease Models, Animal; Diterpenes; Epoxy Compounds; Female; Glucose Tolerance Test; Graft Rejection; Graft Survival; Immunosuppressive Agents; Islets of Langerhans; Islets of Langerhans Transplantation; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred NOD; Phenanthrenes; Time Factors; Transplantation, Homologous; Weight Gain

Extracts of the Chinese medicinal plant, Tripterygium wilfordii, cause reversible infertility in male animals. Sub-fractionation studies have now revealed that the plant extracts contain a number of compounds which are potent antifertility agents in male mammals, including the diterpenes triptolide and tripdiolide and an isomer of the latter. A triptolide, 12,13-chlorohydrin, which is a transformation product formed reversibly by interaction of triptolide with HCl, was also found to be active.

Topics: Animals; Biological Assay; Chromatography, High Pressure Liquid; Diterpenes; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Epoxy Compounds; Fertility; Magnetic Resonance Spectroscopy; Male; Molecular Structure; Organ Size; Phenanthrenes; Rats; Serial Extraction; Sperm Count; Sperm Motility; Spermatocidal Agents; Tablets; Testis; Weight Gain

Topics: Animals; Body Weight; Body Weights and Measures; Nutritional Sciences; Phenanthrenes; Rats; Steroids; Weight Gain