Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Pueraria mirifica Exerts Estrogenic Effect and Promotes Mammary and Endometrial

Anna Kakehashi
* ORCID logo ,
Midori Yoshida
,
Yoshiyuki Tago
,
Naomi Ishii
,
Min Gi
ORCID logo ,
Hideki Wanibuchi
,
Takahiro Okuno
Version 1 : Received: 17 August 2016 / Approved: 17 August 2016 / Online: 17 August 2016 (11:57:56 CEST)
Version 2 : Received: 23 September 2016 / Approved: 26 September 2016 / Online: 26 September 2016 (09:25:39 CEST)

A peer-reviewed article of this Preprint also exists.

Kakehashi, A.; Yoshida, M.; Tago, Y.; Ishii, N.; Okuno, T.; Gi, M.; Wanibuchi, H. Pueraria mirifica Exerts Estrogenic Effects in the Mammary Gland and Uterus and Promotes Mammary Carcinogenesis in Donryu Rats. Toxins 2016, 8, 275. Kakehashi, A.; Yoshida, M.; Tago, Y.; Ishii, N.; Okuno, T.; Gi, M.; Wanibuchi, H. Pueraria mirifica Exerts Estrogenic Effects in the Mammary Gland and Uterus and Promotes Mammary Carcinogenesis in Donryu Rats. Toxins 2016, 8, 275.

Abstract

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.

Keywords

Pueraria mirifica; mammary gland; uterus; carcinogenesis; estrogenic activity; Donryu rat

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Comments (1)

Comment 1
Received: 22 September 2016
Commenter: Dr. I. Sandford Schwartz
Commenter's Conflict of Interests: We are the only manufacturer of a standardized Pueraria mirifica and hold a US patent for it. Our more than a decade of studies are in complete contravention of these findings; however, it is in complete compliance with counterfeit samples, including P. Candolii, sold in Japan inaccurately labeled as P. mirifica.
Comment: This paper suffers from a lack of conformity to standard sections of information normally found in a methods and materials section, such as under "Plant Material" information on the source of the material, batch number, who performed the taxonomic identification, and where the voucher specimen is stored and what the voucher specimen number is. Without this basic information it is not possible to accept such a paper as one has no idea what the authors studied. One can't accept it was what they contend it is, without at least this information, and some chemistry that the material conforms to the major compounds known for that plant material.

The author obtained the test material from Pias, a cosmetic company in Osaka, claiming "they're a large company, so I'm sure they did the proper testing". This made more inscrutable when Japanese Customs published a notice that most of the material labeled Pueraria mirifica, imported into Japan is NOT actually P. mirifica.
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