Isoflavonoid Compounds Extracted from Pueraria lobata Suppress Alcohol Preference in a Pharmacogenetic Rat Model of Alcoholism

Abstract

The extract from an edible vine, Pueraria lobata, has long been used in China to lessen alcohol intoxication. We have previously shown that daidzin, one of the major components from this plant extract, is efficacious in lowering blood alcohol levels and shortens sleep time induced by alcohol ingestion. This study was conducted to test the antidipsotropic effect of daidzin and two other major isoflavonoids, daidzein and puerarin, from Pueraria lobata administered by the oral route. An alcohol-preferring rat model, the selectively-bred P line of rats, was used for the study. All three isoflavonoid compounds were effective in suppressing voluntary alcohol consumption by the P rats. When given orally to P rats at a dose of 100 mg/kg/day, daidzein, daidzin, and puerarin decreased ethanol intake by 75%, 50%, and 40%, respectively. The decrease in alcohol consumption was accompanied by an increase in water intake, so that the total fluid volume consumed daily remained unchanged. The effects of these isoflavonoid compounds on alcohol and water intake were reversible. Suppression of alcohol consumption was evident after 1 day of administration and became maximal after 2 days. Similarly, alcohol preference returned to baseline levels 2 days after discontinuation of the isoflavonoids. Rats receiving the herbal extracts ate the same amounts of food as control animals, and they gained weight normally during the experiments. When administered orally, none of these compounds affected the activities of liver alcohol dehydrogenase and aldehyde dehydrogenase. Therefore, the reversal of alcohol preference produced by these compounds may be mediated via the CNS. Data demonstrate that isoflavonoid compounds extracted from Pueraria lobata is effective in suppressing the appetite for alcohol when taken orally, raising the possibility that other constituents of edible plants may exert similar and more potent actions.

From Herbal Roots to Synthetic Medicines: A Historical Perspective

“…These findings were replicated in rats (Xie et al, 1994). Then several reports appeared that a number of isoflavones isolated from Kudzu root suppressed ethanol intake in Syrian golden hamsters (Keung and Vallee, 1993) and in rats (Lin et al, 1996;Overstreet et al, 1996). The major active compounds that suppressed free-choice drinking were daidzin, daidzein, and puerarin (Lin et al, 1996).…”

“…Then several reports appeared that a number of isoflavones isolated from Kudzu root suppressed ethanol intake in Syrian golden hamsters (Keung and Vallee, 1993) and in rats (Lin et al, 1996;Overstreet et al, 1996). The major active compounds that suppressed free-choice drinking were daidzin, daidzein, and puerarin (Lin et al, 1996). In humans, a study of the efficacy of Kudzu extract containing these three major isoflavones has been performed in heavy drinking subjects.…”

Daidzin inhibits mitochondrial aldehyde dehydrogenase and suppresses ethanol intake of Syrian golden hamsters

“…Puerarin appears to suppress ethanol intake in rats (14,19) but has little or no effect on that in golden hamsters (5,7). This could reflect differences in pharmacokinetic and͞or pharmacodynamic processes of this isoflavone in the two species, or it also could indicate differences in the molecular mechanisms that govern their ethanol drinking.…”

“…The fact that puerarin and two structurally related analogs, chrysin and 7,8-dihydroxyflavone, do not suppress ethanol intake in golden hamsters suggests that a specific mechanism might be involved in the suppression of ethanol drinking in this species. The effects of chrysin and 7,8-dihydroxyflavone on ethanol intake of rats have not been tested (16)(17)(18)(19). Much as comparative studies with hamsters and rats might prove helpful in elucidating the mechanism(s) of action of these antidipsotropic compounds, the ultimate proof of efficacy and safety of the antidipsotropic isoflavones can be achieved only by trials in humans.…”

Synergetic Hepatoprotective Effects of Korean Red Ginseng andPueraria Radixon the Liver Damaged-Induced by Carbon Tetrachloride (CCl4) in Mice

“…, extension of coronary arteries 13 , suppression of lipid peroxidation 14 , detoxification of alcohol 15 , and liver protective functions. 16 While there have been many studies on the hepatoprotective effect of separate administration of RG and PR, there is a lack of studies on comparison and analysis of the effect of combined or mixed administration of RG and PR.…”