Evaluation of the Estrogenic Activity of Pueraria (Kudzu) Flower Extract and Its Major Isoflavones Using ER-Binding and Uterotrophic Bioassays


Pueraria flower extract (PFE) is a hot water extract of the Kudzu flower (Pueraria thomsonii). Tea made from dried Kudzu flower is widely used inChina, and PFE is utilized as a nutritional supplement inJapan. PFE contains unique isoflavones such as 6-hydroxygenistein 6,7-di-O-glucoside (6HGDG), tectorigenin 7-O-xylosylglucoside (TGXG), and tectoridin. 6HGDG is known to be metabolized into 6-hydroxygenistein, and TGXG and tectoridin are known to be metabolized into tectorigenin in the digestive tract. Isoflavones typically mimic the effects β-estradiol has on estrogen receptors (ERs) and may influence the female genital system in the case of excessive intake. As a result, the upper limit of safe daily consumption of soy isoflavones has been enforced inJapan. In the present study, ER-binding assays were performed using the EnBio estrogen receptor/cofactor assay system to compare the estrogenic activity of 6-hydroxygenistein and tectorigenin to that of the soy isoflavone genistein. In addition, uterotrophic bioassays were performed to investigate the estrogenic effects of PFE in vivo. The ER-binding assays revealed that the ER-binding affinities of 6-hydroxygenistein and tectorigenin were approximately 0.01 - 0.04 that of genistein. Soy isoflavone products also induced an increase in uterine wet and blotted weight at doses of 500 mg/kg and 1000 mg/kg, whereas PFE did not cause adverse estrogenic effects, even at a dose of 1000 mg/kg. Based on these results, PFE does not appear to contain compounds with strong estrogenic activity or cause adverse estrogenic effects in vivo. Importantly, the results of this study confirm the safety of PFE as a food supplement.

Share and Cite:

T. Kamiya, A. Takano, Y. Kido, Y. Matsuzuka, M. Sameshima-Kamiya, M. Tsubata, M. Ikeguchi, K. Takagaki and J. Kinjo, "Evaluation of the Estrogenic Activity of Pueraria (Kudzu) Flower Extract and Its Major Isoflavones Using ER-Binding and Uterotrophic Bioassays," Pharmacology & Pharmacy, Vol. 4 No. 2, 2013, pp. 255-260. doi: 10.4236/pp.2013.42036.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Q. Chen, L. Wang and S. Ye, “The Study of Anti-Inflammatory and Anti-Oxidant Effects of the Five Edible Plants,” Journal of Medicinal Plants Research, Vol. 6, No. 17, 2012, pp. 3351-3358. http://www.academicjournals.org/jmpr/pdf/pdf2012/9May/Chen%20et%20al.pdf
[2] T. Kamiya, Y. Matsuzuka, N. Kusaba, M. Ikeguchi, K. Takagaki and K. Kondo, “Preliminary Reseach for the Anti-Obesity Effect of Puerariae Flos Extract in Humans,” Journal of Health Science, Vol. 57, No. 6, 2011, pp. 521-531. doi:10.1248/jhs.57.521
[3] T. Kamiya, A. Takano, Y. Matsuzuka, N. Kusaba, M. Ikeguchi, K. Takagaki and K. Kondo, “Consumption of Pueraria Flower Extract Reduces Body Mass Index via a Decrease in the Visceral Fat Area in Obese Humans,” Bioscience, Biotechnology, and Biochemistry, Vol. 76, No. 8, 2012, pp. 1511-1517. doi:10.1271/bbb.120235
[4] T. Kamiya, M. Sameshima-Kamiya, R. Nagamine, M. Tsubata, M. Ikeguchi, K. Takagaki, T. Shimada and M. Aburada, “The Crude Extract of Puerariae Flower Exerts Antiobesity and Antifatty Liver Effects in High-Fat DietInduced Obese Mice,” Evidence-Based Complementary and Alternative Medicine, 2012, Article ID: 272710. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3368216/
[5] T. Kamiya, R. Nagamine, M. Sameshima-Kamiya, M. Tsubata, M. Ikeguchi and K. Takagaki, “The Isoflavone-Rich Fraction of the Crude Extract from Puerariae Flower Increases Oxygen Consumption and BAT UCP1 Expression in High-Fat Diet-Fed Mice,” Global Journal of Health Science, Vol. 4, No. 5, 2012, pp. 147-155. doi:10.5539/gjhs.v4n5p147
[6] L. Rowland, M. Faughnan, L. Hoey, K. Wähälä, G. Williamson and A. Cassidy, “Bioavailability of Phyto-Oestrogens,” The British Journal of Nutrition, Vol. 89, No. 1, 2003, pp. S45-S58.
[7] K. Hiramaya, Y. Matsuzuka, T. Kamiya, M. Ikeguchi, K. Takagaki and K. Itoh, “Metabolism of Isoflavones Found in the Pueraria thomsonii Flower by Human Intestinal Microbiota,” Bioscience Microflora, Vol. 30, No. 4, 2011, pp. 135-140.
[8] R. Tsuchihasi, M. Kodera, S. Sakamoto, Y. Nakajima, T. Yamazaki, Y. Niiho, T. Nohara and J. Kinjo, “Microbial Transformation and Bioactivation of Isoflavones from Pueraria Flowers by Human Intestinal Bacterial Strains,” Journal of Natural Medicine, Vol. 63, No. 3, 2009, pp. 254-260. doi:10.1007/s11418-009-0322-z
[9] M. S. Anthony, T. B. Clarkson, C. L. Hughes, T. M. Morgan and G. L. Burke, “Soybean Isoflavones Improve Cardiovascular Risk Factors without Affecting the Reproductive System of Peripubertal Rhesus Monkeys,” The Journal of Nutrition, Vol. 126, No. 1, 1996, pp. 43-50.
[10] J. J. Anderson, W. W. Ambrose and S. C. Garner, “Biphasic Effects of Genistein on Bone Tissue in the Ovariectomized, Lactating Rat Model,” Proceedings of the Society for Experimental Biology and Medicine, Vol. 217, No. 3, 1998, pp. 345-350.
[11] Y. H. Ju, C. D. Allred, K. F. Allred, K. L. Karko, D. R. Doerge and W. G. Helferich, “Physiological Concentrations of Dietary Genistein Dose-Dependently Stimulate Growth of Estrogen-Dependent Human Breast Cancer (MCF-7) Tumors Implanted in Athymic Nude Mice,” The Journal of Nutrition, Vol. 131, No. 11, 2001, pp. 29572962.
[12] L. J. Lu, K. E. Anderson, J. J. Grady, F. Kohen and M. Nagamani, “Decreased Ovarian Hormones during a Soya Diet: Implications for Breast Cancer Prevention,” Cancer Research, Vol. 60, No. 15, 2000, pp. 4112-4121.
[13] J. Kanno, L. Onyon, J. Haseman, P. Fenner-Crisp, J. Ashby and W. Owens, “The OECD Program to Validate the Rat Uterotrophic Bioassay to Screen Compounds for in Vivo Estrogenic Responses: Phase 1,” Environmental Health Perspectives, Vol. 109, No. 8, 2001, pp.785-794. doi:10.1289/ehp.01109785
[14] S. Y. Choi, T. Y. Ha, J. Y. Ahn, S. R. Kim, K. S. Kang, I. K. Hwang and S. Kim, “Estrogenic Activities of Isoflavones and Flavones and Their Structure-Activitiy Relationships,” Planta Medica, Vol. 74, No. 1, 2007, pp. 2532. doi:10.1055/s-2007-993760
[15] T. Zacharewski, “Identification and Assesement of Endocrine Disruptors: Limitations of in Vivo and in Vitro Assays,” Environmental Health Perspectives, Vol. 106, No. 2, 1998, pp. 577-582. doi:10.1289/ehp.98106577
[16] W. N. Jefferson, E. Padilla-Banks, G. Clark and R. R. Newbold, “Assesing Estrogenic Activity of Phytochemicals Using Transcriptional Activation and Immature Mouse Uterotrophic Responses,” Journal of Chromatography B. Analytical Technologies in the Biomedical and Life Science, Vol. 777, No. 1-2, 2002, pp. 179-189.
[17] S. Chansakaow, T. Ishikawa, H. Seki, K. Sekine-Yoshizawa, M. Okada and C. Chaichantipyuth, “Identification of Deoxymi-roesterol as the Actual Rejuvenating Principle of “Kwao Keur”, Pueraria Mirifica. The Known Miroesterol May Be an Artifact,” Journal of Natural Products, Vol. 63, No. 2, 2000, pp. 173-175. doi:10.1021/np990547v
[18] A. Matumura, A. Ghosh, G. S. Pope and P. D. Darbre, “Comparative Study of Oestrogenic Properties of Eight Phytoestrogens in MCF7 Human Breast Cancer Cells,” The Journal of Steroid Biochemistry and Molecular Biology, Vol. 94, No. 5, 2005, pp. 431-443. doi:10.1016/j.jsbmb.2004.12.041
[19] H. E. Jones and G. S. Pope, “A Study of the Action of Miroestrol and Other Oestrogens on the Reproductive Tract of the Immature Female Mouse,” The Journal of Endocrinology, Vol. 20, 1960, pp. 229-235. doi:10.1677/joe.0.0200229
[20] H. Trisomboon, S. Malaivijitnond, G. Watanabe and K. Taya, “Ovulation Block by Pueraria Mirifica: A Study of Its Endocrinological Effect in Female Monkeys,” Endocrine, Vol. 26, No. 1, 2005, pp. 33-39. doi:10.1385/ENDO:26:1:033

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.