Abstract
Pueraria mirifica (PM), a plant whose dried and powdered tuberous roots are now widely used in rejuvenating preparations to promote youthfulness in both men and women, may have major estrogenic influence. In this study, we investigated modifying effects of PM at various doses on mammary and endometrial carcinogenesis in female Donryu rats. Firstly, PM administered to ovariectomized animals at doses of 0.03%, 0.3%, and 3% in a phytoestrogen-low diet for 2 weeks caused significant increase in uterus weight. Secondly, a 4 week PM application to non-operated rats at a dose of 3% after 7,12-dimethylbenz[a]anthracene (DMBA) initiation resulted in significant elevation of cell proliferation in the mammary glands. In a third experiment, postpubertal administration of 0.3% (200 mg/kg body weight (b.w.)/day) PM to 5-week-old non-operated animals for 36 weeks following initiation of mammary and endometrial carcinogenesis with DMBA and N-ethyl-N′-nitro-N-nitrosoguanidine (ENNG), respectively, resulted in significant increase of mammary adenocarcinoma incidence. A significant increase of endometrial atypical hyperplasia multiplicity was also observed. Furthermore, PM at doses of 0.3%, and more pronouncedly, at 1% induced dilatation, hemorrhage and inflammation of the uterine wall. In conclusion, postpubertal long-term PM administration to Donryu rats exerts estrogenic effects in the mammary gland and uterus, and at a dose of 200 mg/kg b.w./day was found to promote mammary carcinogenesis initiated by DMBA.
Highlights
Pueraria mirifica (PM), known as white Kwao Krua, is a plant found in northern and northeastern Thailand which belongs to the family of Leguminosae, and the soy, bean, and pea subfamily Papilionoideae
Measured mammary adenocarcinoma volumes were elevated in the 0.03, 0.3, and 1% PM and 0.2% isoflavone aglycon (IA) groups starting from week 16 as compared to the initiation control rats, with the highest value observed in the 0.03% PM dose group and the lowest increase induced by PM at a dose of 1% (Figure 3E)
The present results demonstrated that long-term postpubertal exposure to PM at doses higher than
Summary
Pueraria mirifica (PM), known as white Kwao Krua, is a plant found in northern and northeastern Thailand which belongs to the family of Leguminosae, and the soy, bean, and pea subfamily Papilionoideae. PM is available in tablets, extracts, creams, sprays, and powdered forms, so that it can be added to other medicinal preparations or herbs, and individual conditions require different applications and dosages [1] It can be readily obtained from internet resources in many countries, including the USA and Japan, and is primarily used for supporting memory, smoothing the skin, increasing hair growth, improving appetite, and providing relief for ailments like osteoporosis and even cancer [9,10,11,12]. We further demonstrated that postpubertal administration of soy isoflavones at estrogenic doses promotes mammary and endometrial carcinogenesis in Donryu rats [15] These data call into question the safety of long-term exposure to phytoestrogens with regard to effects on the mammary gland and endometrium. The present study was carried out to investigate the modifying effects of various doses of PM on mammary and uterine endometrial carcinogenesis using the Donryu rat model
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