DISRUPTION OF MITOCHONDRIAL MEMBRANE POTENTIAL BY FERULENOL AND RESTORATION BY PROPOLIS EXTRACT: ANTIAPOPTOTIC ROLE OF PROPOLIS

This paper reports an investigation of the ability of propolis extract (a resinous substance collected by honeybees from various plant sources) to restore the collapse of mitochondrial membrane potential induced by ferulenol, a sesquiterpene prenylated coumarin derivative isolated from the plant Ferula vesceritensis. We show that ferulenol was able to induce the permeability transition pore (PTP) opening. This effect is caused by the interaction of the compound with the mitochondrial respiratory chain, more particularly by the fall of membrane potential and the inhibition of complex II. We have previously demonstrated that this inhibition results from a limitation of electron transfers involved in the respiratory chain and initiated by the reduction of ubiquinone. We hypothesized that the protective effect of propolis could be due to a direct action on mitochondrial functions. So we have investigated in vitro the mitochondrial effects of Algerian propolis using rat liver mitochondria, by analysing their effects on membrane potential, mitochondrial respiration and mitochondrial swelling. We show that propolis extract was able to restore the fall of mitochondrial membrane potential. Taken together these data reveal that propolis extract may be an interesting inhibitor of PTP and provide an additional mechanism by which the natural product propolis extract may restore the mitochondrial membrane potential and to prevent apoptotic process.