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.
The sub-acute toxicity of E. faecalis HZNU P2 was investigated in rats fed with different doses for 14 days. To evaluate the acute oral toxicity of E. faecalis HZNU P2, rats were fed with E. faecalis HZNU P2 at a high dose of 2×10 11 CFU kg -1 for 10 days. Results showed that there were no abnormal clinical signs in any of the groups during the experiment. There were no signifi cant differences in live weight gain among rats fed with E. faecalis HZNU P2, compared to those in control group. Macroscopic or microscopic examinations of organs revealed no abnormalities, indicating that E. faecalis HZNU P2 did not adversely affect the health of rats. Results of this study demonstrated that digestion of E. faecalis HZNU P2 in rats did not show any obvious signs of toxicity.
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