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Inhibition of Mitochondrial Respiratory Chain Activity by O, O-Dimethyl- and 4-O- Methyl- Alpinumisoflavones

Augustine Ocloo; Robert Kingsford-Adaboh; Andrew J. Murray.

Abstract
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 fibres 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 glabrescen sinhibits mitochondria respiratory complexes I, II and IV.

Key words: mitochondrial respiratory complexes;inhibition;alpinumisoflavones



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