Pueraria <em>mirifica</em> Exerts Estrogenic Effect and Promotes Mammary and Endometrial

Pueraria mirifica (PM) is a plant which dried and powdered tuberous root is now widely used as a rejuvenating herb to promote youthfulness in both men and women. In this study, we investigated the modifying effects of PM at various doses on mammary and endometrial carcinogenesis in female Donryu rats. Firstly, PM administered to ovariectomized Donryu rats at doses of 0.03, 0.3 and 3% in phytoestrogen-low diet for 2 weeks induced the significant increases of uterus weight. Secondly, 4-week PM application to non-operated rats at a dose of 3% after the 7,12-dimethylbenz[a]anthracene (DMBA) initiation, resulted in significant elevation of cell proliferation in the mammary glands. In the third experiment, postpubertal administration of 0.3% (200 mg/kg b.w./day) PM to 5-week-old non-operated animals for 36 weeks following the initiation of mammary and endometrial carcinogenesis with DMBA and N-ethyl-N′-nitro-N-nitrosoguanidine (ENNG), respectively, caused significant increases of mammary adenocarcinoma incidence and multiplicity. A trend for increase of uterine adenocarcinomas and a significant increase of endometrial atypical hyperplasia multiplicity was observed at 0.3% PM. Furthermore, PM at doses of 0.3 and mostly 1% induced dilatation, hemorrhage and inflammation of the uterine wall. In conclusion, the postpubertal long-term PM administration to Donryu rats exerted estrogenic effect in the mammary gland and uterus, and at a dose of 200 mg/kg b.w./day promoted carcinogenesis initiated by DMBA and ENNG.