Toxicological evaluation of the isoflavone puerarin and its glycosides

Puerarin, an isoflavone derived from kudzu roots, has strong biological activities. However, its bioavailability in vivo is often limited by its insolubility. A novel transglycosylase increases the solubility of puerarin >100-fold, by converting it to puerarin glycosides. Since over-consumption of an isoflavone might have toxic effects, therefore, we investigated the potential antimutagenic activity, bone marrow micronucleus test, and a 28-day oral repeated administration test with puerarin and its glycosides. In Ames tests, neither puerarin nor its glycosides exhibited mutagenic effects up to 200 μg/plate. Puerarin and its glycoside, glucosyl-α-(1,6)-puerarin, significantly reduced the mutagenic effect of 4-nitroquinoline-1-oxide by up to 41%. In bone marrow micronucleus tests using ICR mice, neither puerarin nor glucosyl-α-(1,6)-puerarin interfered with erythrocyte production in the bone marrow. Both compounds decreased the prevalence of polychromatic erythrocytes. Sprague-Dawley rats were orally dosed with puerarin and its glycosides daily for 28 days. Neither puerarin nor its glycosides caused significant alterations in histology, and biochemical and hematologic parameters. These results suggest that puerarin and its glycosides do not have significant toxic effects, at least in rodents, either in vitro or in vivo at doses of up to 250 mg/kg per day.