in vitro evaluation of inhibitory effect of artemisinin and dihydroartemisinin on calcineurin enzyme

background and objective: artimisinin (an anti-malaria drug) is extracted from artemisia annua and its water soluble derivative is dihydroartimisinin. previous in vivo and in vitro studies showed that it has an inhibitory effect on t cells. it is also useful for immunosuppression of immune system. materials and methods: the stable state kinetic for comparison of inhibitory effect of artimisinin, dihydroartimisinin and cyclosporine a on calcineurin activation was used in this study. first, the best inhibitory concentration of artimisinin, dihydroartimisinin and cyclosporine a was calculated. afterwards, the km and vmax of them in the presence of substrate, paranitrophenylphosphate (p-npp) were measured. the ki was calculated in the presence of cyclosporine a, artemisinin and dihydroartemisinin. in this study, we used distilled water instead of sample in blank and cyclosporina as a positive control group. results: the vmax in the control group was 81.97 m/min and in the presence of cyclosporine a and artemisinin or dihydroartemisinin were 81.97 m/min and 66.225 m/min, respectively. the km in the absence of inhibitors was 1.886 m and in the presence of cyclosporine a and artemisinin or dihydroartemisinin was 2.819 m and 1.736, respectively. also, ­ki in the presence of artimisinin and dihydroartimisinin was 4.219 ×10-5 m and in the presence of cyclosporine a was 2.021×10-5 m. conclusion: this study indicates that the inhibitory power of artimisinin and dihydroartimisinin is almost equal and they inhibited calcineurin competitively, while inhibitory effect of cyclosporine a is non-competitive.