Uncoupling of respiration and inhibition of ATP synthesis in mitochondria by C-methylated flavonoids from Myrica gale L.

Abstract

The uncoupling activity of seven C-methylated flavonoids from the fruits of Myrica gale L. was studied. Myrigalone A, B and G (MyA, MyB and MyG) uncoupled the oxidative phosphorylation in rat liver mitochondria. MyA was most potent, at 45 μM causing an increase of 87±8 natoms O/min/mg in the state 4 respiration rate, which is more than twice the effect of 2,4-dinitrophenol (DNP). MyG was slightly less active than MyA, but its activity decreased from 45 to 90 μM. MyB was approximately equipotent with DNP. Myrigalone D and H were weak uncouplers, whereas myrigalone E and angoletin were inactive. The uncoupling activity of MyA, MyB and MyG was accompanied by an inhibitory effect on the ATP synthesis. The inhibition caused by MyA at 45 μM was about 70%. Whereas the effect of MyA or MyB was nearly constant throughout the incubation period, the effect of MyG had almost vanished after 15 min. The uncoupling activity of the myrigalones does not seem to be related to their antioxidative properties.