Department of Pharmaceutics and Ernest Mario School of Pharmacy, Rutgers The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, New Jersey 08854, USA.
Pharm Res. 2009 Oct;26(10):2324-31. doi: 10.1007/s11095-009-9948-5. Epub 2009 Aug 8.
In the present study, we have evaluated the pharmacokinetics and the in vivo prostate chemopreventive activity of broccoli sprouts.
The in vivo pharmacokinetic profiles of sulforaphane (SFN) and SFN- glutathione (GSH) conjugate in rats after oral administration of 200 mg and 500 mg broccoli sprouts were analyzed. Next, 8-week old TRAMP mice were fed with dietary broccoli sprouts at two dosages (60 and 240 mg/mouse/day) for 16 weeks, and the mice were sacrificed to examine the pharmacodynamic response on prostate tumor and some biomarkers.
SFN was readily released and conjugated with GSH in the rats after oral administration of broccoli sprouts. TRAMP mice fed with 240 mg broccoli sprouts/mouse/day exhibited a significant retardation of prostate tumor growth. Western blot analysis revealed that the expression levels of Nrf2, HO-1, cleaved-Caspase-3, cleaved-PARP and Bax proteins were increased, but that of Keap1 and Bcl-XL proteins were decreased. In addition, the phosphorylation and/or the expression level of Akt and its downstream kinase and target proteins, e.g. mTOR, 4E-BP1 and cyclin D1, were reduced.
Our findings indicate that broccoli sprouts can serve as a good dietary source of SFN in vivo and that they have significant inhibitory effects on prostate tumorigenesis.
本研究评估了西兰花芽的药代动力学和体内前列腺化学预防活性。
分析了大鼠口服 200mg 和 500mg 西兰花芽后，体内萝卜硫素（SFN）和 SFN-谷胱甘肽（GSH）缀合物的药代动力学特征。然后，将 8 周龄 TRAMP 小鼠用两种剂量（60 和 240mg/只/天）的西兰花芽进行饮食喂养 16 周，然后处死小鼠，检查前列腺肿瘤和一些生物标志物的药效反应。
西兰花芽口服后，SFN 迅速释放并与 GSH 结合。每天 240mg 西兰花芽喂养的 TRAMP 小鼠前列腺肿瘤生长明显延迟。Western blot 分析显示，Nrf2、HO-1、cleaved-Caspase-3、cleaved-PARP 和 Bax 蛋白的表达水平增加，而 Keap1 和 Bcl-XL 蛋白的表达水平降低。此外，Akt 及其下游激酶和靶蛋白（如 mTOR、4E-BP1 和 cyclin D1）的磷酸化和/或表达水平降低。
我们的研究结果表明，西兰花芽可以作为体内 SFN 的良好膳食来源，对前列腺肿瘤发生具有显著的抑制作用。
