Zhang Yan, Zhou Li-Ping, Li Xiao-Li, Zhao Yong-Jian, Ho Ming-Xian, Qiu Zuo-Cheng, Zhao Dong-Feng, Mok Daniel Kam-Wah, Shi Qi, Wang Yong-Jun, Wong Man-Sau
Spine Research Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, PRC.
State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, PRC.
Oncotarget. 2018 Mar 19;9(36):24221-24236. doi: 10.18632/oncotarget.24823. eCollection 2018 May 11.
Our previous study reported that the 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.
我们之前的研究报告称，8-异戊烯基染料木黄酮（8PG）的成骨作用比其母体化合物染料木黄酮更强。本研究旨在评估8PG对去卵巢（OVX）小鼠的骨保护作用，并表征其在子宫中的雌激素样作用。将成熟的OVX小鼠用含8PG或染料木黄酮的无植物雌激素饮食进行处理。在用染料木黄酮和两种剂量的8PG处理后，OVX小鼠股骨远端干骺端的小梁骨量和大多数微观结构参数均得到改善。番红O和ABHO染色证实了8PG对小梁骨的有益作用。8PG显著抑制去卵巢诱导的骨中RANKL/OPG、ALP、COL、OCN、组织蛋白酶K和ER-α的mRNA表达。相比之下，染料木黄酮进一步增加了去卵巢诱导的骨中ER-α的表达。染料木黄酮处理组的子宫指数增加。染料木黄酮上调了ER-α和PR的表达，而8PG显著下调了OVX小鼠子宫中ER-α和C3的表达。此外，染料木黄酮而非8PG增加了Ishikawa细胞中ER-α、PCNA和C3的表达。本研究表明，8PG改善了OVX小鼠的小梁骨特性，而不产生子宫营养作用，并且其雌激素样作用与染料木黄酮不同。
