Effect of a prenylated flavonoid on the activities of membrane-bound enzymes and on mitochondrial membrane potential,

ELINGOLDI, CASANOVA MB, CELENTANO AM, TABOAS M, PÉREZ C, CABRERA JL, DIEZ RA, DUBIN M.

Buenos Aires

Congreso; XXXIX Reunion Anual de la Sociedad Argentina de Farmacología Experimental; 2007

Sociedad Argentina de Farmacología Experimental

Effect of a prenylated flavonoid on the activities of membrane-bound enzymes and on mitochondrial membrane potential. Elingold I1, Casanova MB1, Celentano AM2, Taboas M1 ,Pérez C3, Cabrera JL4, Diez RA5, Dubin M1. 1CEFYBO UBA-CONICET, Dptos. 2Microbiología y  5Farmacología, Facultad de Medicina, 3Cát.Farmacología, Fac. Odontología (UBA) y 4Farmacognosia, Facultad de Ciencias Químicas(UNC).dubin@mail.retina.ar                                                         The prenylated flavonoid 2´-4´-dihidroxy-5´-(1´´´-dimethylallyl)-6-prenylpinocembrin (6PP), obtained from Dalea elegans, shows antimicrobial activity. Previous results of 6PP showed dose-dependent anti-radical, and antioxidant activities. 6PP, also inhibited and/or uncoupled mitochondrial respiration and  inhibited F0F1 ATPase activity (Elingold et al, SAIC 2006). We study the effect of 6PP on succinate deshidrogenase (SDH) and NADH-oxidase activities and mitochondrial membrane potential (MMP). 6PP promoted significantly inhibition of SDH and NADH oxidase activity in a concentration-dependent manner (IC50 of 25 µM and 19 μM respectively). The effect of 6PP on MMP was investigated in coupled mitochondria and was measured by rhodamine 123 fluorescence. Using malate-glutamate as substrate, 6PP (50 µM) significantly decreased 32% MMP after 25 min incubation, while 6PP (100 µM) significantly decreased by 47.5 and 56% MMP for 10 or 25 min incubation, respectively With succinate as substrate, 6PP (50 and 100 µM) decreased MMP by 33 and 48.4% respectively after 10 min incubation. On the other hand, 6PP (25, 50 and 100 µM) decreased  MMP for 25 min incubation (34.4, 55 and 56%, respectively). In summary, we have partially characterized the activity of the prenylated flavonoid 6PP, demonstrating its toxic effects on isolated rat liver mitochondria.