Oncotarget

Research Papers:

8-Prenylgenistein, a prenylated genistein derivative, exerted tissue selective osteoprotective effects in ovariectomized mice

Yan Zhang _, Li-Ping Zhou, Xiao-Li Li, Yong-Jian Zhao, Ming-Xian Ho, Zuo- Cheng Qiu, Dong-Feng Zhao, Daniel Kam-Wah Mok, Qi Shi, Yong-Jun Wang and Man-Sau Wong

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Oncotarget. 2018; 9:24221-24236. https://doi.org/10.18632/oncotarget.24823

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Abstract

Yan Zhang1,2,3, Li-Ping Zhou4, Xiao-Li Li5, Yong-Jian Zhao1,3, Ming-Xian Ho4, Zuo-Cheng Qiu6, Dong-Feng Zhao1,3, Daniel Kam-Wah Mok4, Qi Shi1,3, Yong-Jun Wang1,3,7 and Man-Sau Wong2,4

1Spine Research Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, PRC

2State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, PRC

3Key Laboratory of Theory and Therapy of Muscles and Bones of Ministry of Education, Shanghai, PRC

4Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, PRC

5School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai, PRC

6Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou, PRC

7School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, PRC

Correspondence to:

Man-Sau Wong, email: man-sau.wong@polyu.edu.hk

Yong-Jun Wang, email: yjwang8888@126.com

Keywords: genistein; 8-prenylgenistein; bone; estrogenic effects; uterus

Received: June 03, 2017     Accepted: September 23, 2017     Epub: March 19, 2018     Published: May 11, 2018

ABSTRACT

Our previous study reported that the in vitro osteogenic effects of 8-prenylgenistein (8PG) were more potent than its parent compound genistein. This study aimed to evaluate the osteoprotective effects of 8PG in ovariectomized (OVX) mice as well as to characterize its estrogenic effects in uterus. Mature OVX mice were treated with phytoestrogen-free diet containing 8PG or genistein. Trabecular bone mass and most of the micro-structural parameters were ameliorated at the distal femoral metaphysis in OVX mice upon treatment with genistein and both doses of 8PG. The beneficial effects of 8PG on trabecular bone were confirmed by safranin O and ABHO staining. 8PG markedly inhibited the ovariectomy-induced mRNA expressions of RANKL/OPG, ALP, COL, OCN, cathepsin K and ER-α in bone. In contrast, genistein further increased the ovariectomy-induced ER-α expression in bone. The uterus index was increased in genistein-treated group. Genistein up-regulated the expression of ER-α and PR, while 8PG significantly down-regulated the ER-α and C3 expression in uterus of OVX mice. Moreover, genistein, but not 8PG, increased expressions of ER-α, PCNA and C3 in Ishikawa cell. This study suggested that 8PG improved trabecular bone properties in OVX mice without exerting uterotrophic effects and its estrogenic actions were distinct from those of genistein.


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