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eCAM Advance Access originally published online on May 17, 2007
eCAM 2008 5(3):295-302; doi:10.1093/ecam/nem036
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© 2007 The Author(s).
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Estrogenic Activities of Fatty Acids and a Sterol Isolated from Royal Jelly

Kazu-Michi Suzuki1, Yoichiro Isohama2, Hiroe Maruyama1, Yayoi Yamada1, Yukio Narita1, Shozo Ohta1, Yoko Araki1, Takeshi Miyata2,3 and Satoshi Mishima1

1Nagaragawa Research Center, API Co., Ltd, 692-3 Nagara, Gifu 502-0071 and 2Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Kumamoto 862-0973, Japan

We have previously reported that royal jelly (RJ) from honeybees (Apis mellifera) has weak estrogenic activity mediated by interaction with estrogen receptors that leads to changes in gene expression and cell proliferation. In this study, we isolated four compounds from RJ that exhibit estrogenic activity as evaluated by a ligand-binding assay for the estrogen receptor (ER) β. These compounds were identified as 10-hydroxy-trans-2-decenoic acid, 10-hydroxydecanoic acid, trans-2-decenoic acid and 24-methylenecholesterol. All these compounds inhibited binding of 17β-estradiol to ERβ, although more weakly than diethylstilbestrol or phytoestrogens. However, these compounds had little or no effect on the binding of 17β-estradiol to ER{alpha}. Expression assays suggested that these compounds activated ER, as evidenced by enhanced transcription of a reporter gene containing an estrogen-responsive element. Treatment of MCF-7 cells with these compounds enhanced their proliferation, but concomitant treatment with tamoxifen blocked this effect. Exposure of immature rats to these compounds by subcutaneous injection induced mild hypertrophy of the luminal epithelium of the uterus, but was not associated with an increase in uterine weight. These findings provide evidence that these compounds contribute to the estrogenic effect of RJ.

Keywords: Apis mellifera – 2-Decenoic acid – 10-Hydroxydecanoic acid – 10-Hydroxy-2-decenoic acid – 24-Methylenecholesterol


For reprints and all correspondence: Kazu-Michi Suzuki, Nagaragawa Research Center, API Co., Ltd, 692-3 Nagara, Gifu 502-0071, Japan. Tel: +81-58-232-0838; Fax: +81-58-294-8388; E-mail: suzuki-kazumichi{at}api3838.co.jp

3Present address: Faculty of Pharmacy, Sojo University, 4-22-1 Ikeda, Kumamoto 860-0082, Japan.

Received September 5, 2006; accepted December 5, 2006


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