Therapeutic lessons from traditional Oriental medicine to contemporary Occidental pharmacology.
An extract of Radix Puerariae (RP), an herb long used in traditional Chinese medicine for alcohol addiction and intoxication, was shown to suppress the free-choice ethanol intake of ethanol-preferring Syrian golden hamsters. Two isoflavones, diadzein (4',7-dihydroxyisoflavone) and daidzin (7-glucoside of daidzein), isolated from the extract were shown to account for this effect. Daidzin administered intraperitoneally at 150 mg/kg/day suppressed free-choice ethanol intake by > or = 50%. Such effect has been confirmed in a total of 79 consecutive hamsters studied over a period of more than a year. Daidzein was less potent and a higher dose (230 mg/kg/day) was required to produce similar effect. RP-, daidzin-, and daidzein-treated hamsters appeared to remain healthy and exhibited no significant change in body weight and water or food intake. In vitro, daidzin and daidzein inhibited human mitochondrial aldehyde dehydrogenase (ALDH-2) and gamma gamma-alcohol dehydrogenase (gamma gamma-ADH), respectively. However, at doses that suppressed ethanol intake, daidzin and daidzein had no effect on overall acetaldehyde and ethanol metabolism in hamsters. These findings clearly distinguish the action(s) of daidzin and daidzein from those of the classic, broad acting inhibitors of ALDH (e.g. disulfiram) and class I ADH isozymes (e.g. 4-methylpyrazole), and identify them as a new class of compounds that offer promise as safe and effective therapeutic agents for alcohol abuse.
Center for Biochemical and Biophysical Sciences and Medicine, Harvard Medical School, Boston, MA 02115.
W M
WM
Keung
B L
BL
Vallee
D000079:Acetaldehyde / Q000378:metabolism; D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000428:Alcohol Drinking / Q000517:prevention & control*; D000818:Animals; D002755:Choice Behavior / Q000187:drug effects*; D006224:Cricetinae; D004221:Disulfiram / Q000494:pharmacology; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology; D000431:Ethanol / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D008297:Male; D008516:Medicine, Chinese Traditional; D008647:Mesocricetus; D010936:Plant Extracts / Q000494:pharmacology
D004968:Estrogens, Non-Steroidal; D005419:Flavonoids; D007529:Isoflavones; D010936:Plant Extracts; D000431:Ethanol; C013908:daidzin; C004742:daidzein; D000426:Alcohol Dehydrogenase; D000079:Acetaldehyde; D004221:Disulfiram; C033607:puerarin