Biogenic aldehyde(s) derived from the action of monoamine oxidase may mediate the antidipsotropic effect of daidzin.
Daidzin, a major active principle of an ancient herbal treatment for 'alcohol addiction', was first shown to suppress ethanol intake in Syrian golden hamsters. Since then this activity has been confirmed in Wistar rats, Fawn hooded rats, genetically bred alcohol preferring P rats and African green moneys under various experimental conditions, including two-level operant, two-bottle free-choice, limited access, and alcohol-deprivation paradigms. In vitro, daidzin is a potent and selective inhibitor of mitochondrial aldehyde dehydrogenase (ALDH-2). However, in vivo, it does not affect overall acetaldehyde metabolism in golden hamsters. Using isolated hamster liver mitochondria and 5-hydroxytryptamine (5-HT) and dopamine (DA) as the substrates, we demonstrated that daidzin inhibits the second but not the first step of the MAO/ALDH-2 pathway, the major pathway that catalyzes monoamine metabolism in mitochondria. Correlation studies using structural analogs of daidzin led to the hypothesis that the mitochondrial MAO/ALDH-2 pathway may be the site of action of daidzin and that one or more biogenic aldehydes such as 5-hydroxyindole-3-acetaldehyde (5-HIAL) and/or DOPAL derived from the action of monoamine oxidase (MAO) may be mediators of its antidipsotropic action.
Keung
W M
WM
Center for Biochemical and Biophysical Sciences and Medicine, Harvard Medical School, 250 Longwood Avenue, 02115, Boston, MA, USA. wingming_keung@hms.harvard.edu
D015102:3,4-Dihydroxyphenylacetic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D000427:Alcohol Deterrents / Q000494:pharmacology*; D000428:Alcohol Drinking / Q000188:drug therapy / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000447:Aldehydes / Q000378:metabolism*; D000818:Animals; D002522:Chlorocebus aethiops; D006224:Cricetinae; D004298:Dopamine / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D066298:In Vitro Techniques; D007529:Isoflavones / Q000494:pharmacology*; D008647:Mesocricetus; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000378:metabolism
D000427:Alcohol Deterrents; D000447:Aldehydes; D004791:Enzyme Inhibitors; D007529:Isoflavones; D008996:Monoamine Oxidase Inhibitors; D015102:3,4-Dihydroxyphenylacetic Acid; C004277:hydroxyindoleacetaldehyde; D012701:Serotonin; C013908:daidzin; D006897:Hydroxyindoleacetic Acid; C007430:3,4-dihydroxyphenylacetaldehyde; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D008995:Monoamine Oxidase; D004298:Dopamine