Baohuoside-1, a novel immunosuppressive molecule, inhibits lymphocyte activation in vitro and in vivo |
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Authors: | Ma Anlun Qi Shijie Xu Dasheng Zhang Xiaochun Daloze Pierre Chen Huifang |
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Institution: | Laboratory of Experimental Surgery, Research Center of Center Hospitalier de l'Université de Montréal, Notre-Dame Hospital, University of Montreal, Montreal, Quebec, Canada. |
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Abstract: | BACKGROUND: We evaluated the in vitro and in vivo immunosuppressive effects of baohuoside-1 (B1), a novel flavonoid isolated from Epimedium davidii. METHODS: Proliferation assay was used to determine the antiproliferative properties on T-cell and B-cell proliferation. Flow cytometry analysis was applied to detect changes of phenotypes on activated cells. RESULTS: B1 inhibits the lymphocyte proliferation activated by polyclonal mitogens and mixed lymphocyte reaction with a 50% inhibitory concentration of low micromolar concentration. Also, B1 suppressed T-cell activation in T cell receptor/CD3-mediated signaling pathways in a dose- and time-dependent manner. The suppression of B1 was not simply a result of a toxic effect and was recovered by withdrawing the drug. B1 down-regulated the expression of some phenotype molecules. In Ca(2+)-independent or -dependent antigen stimulation, although B1 had different inhibitive patterns on CD69 expression stimulated by phorbol 12-myristate 13-acetate (PMA) or Ca2+ ionophore, it inhibited T-cell proliferation induced by CD3/CD28 or PMA/ionomycin and partially blocked that induced by PMA/CD28. Interestingly, an additive inhibition between B1 and tacrolimus (FK506) was found in the CD69 expression stimulated by PMA/CD28 and PMA/ionomycin. Similarly, this immunosuppression by combination therapy was observed in a heart transplantation model in vivo and might act through an immunosuppressive mechanism different from FK506. CONCLUSIONS: B1, whose mechanism of action is not similar to that of FK506, has selectively immunosuppressive effects on T-cell and B-cell activation in vitro and effectively prevents rat heart allograft rejection in vivo. |
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