Inhibition of mitochondrial respiratory chain activity by O, O-dimethyl- and 4-o- methyl- alpinumisoflavones

Although the molluscicidal activity of crude dichloromethane extract of Millettia thonningii, known to be rich in alpinumisoflavones was attributed to its inhibition of isolated rat liver mitochondrial complex I activity, the effects of the constituent alpinuisoflavones on mitochondrial function have not been reported. The present study, therefore investigated the effect of O, O-dimethyl-alpinumisoflavone, a constituent of the crude dichloromethane extract of M. thonningii seeds and 4'-O-methyl-alpinumsioflavone, a naturally occurring alpinumisoflavone in Lonchocarpus glabrescens in isolated rat liver mitochondria and permeabilised mouse heart fibers using substrate-inhibitor titrations. The O, O-dimethyl-alpinumisoflavone inhibited State 3 respirations supported by glutamate/malate (complex I), succinate (complex II) and Ascorbate/TMPD (complex IV) in the permeabilised cardiac tissues but inhibited only the State 3 respiration supported by glutamate (complex I) in the isolated rat liver mitochondria. The 4'-O-methyl-alpinumsioflavone on the other hand inhibited State 3 respirations supported by all the substrates in both the isolated rat liver mitochondria and the permeabilised cardiac tissues. Thus, whilst O, O-dimethyl-alpinumisoflavone, a naturally occurring phyto-compound in the extract of M. thonningii seeds inhibits mitochondrial respiratory chain activity essentially at complex I, its derivative 4'-O-methyl-alpinumisoflavone, a naturally occurring phytocompound in Lonchocarpus glabrescens inhibits mitochondrial respiratory complexes I, II and IV.