UIC/NIH Center for Botanical Dietary Supplements Research, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, IL 60612, USA.
Mol Nutr Food Res. 2013 Jun;57(6):1055-66. doi: 10.1002/mnfr.201200534. Epub 2013 Mar 20.
Hops contain the phytoestrogen, 8-prenylnaringenin, and the cytoprotective compound, xanthohumol (XH). XH induces the detoxification enzyme, NAD(P)H-quinone oxidoreductase (NQO1) in vitro; however, the tissue distribution of XH and 8-prenylnaringenin and their tissue-specific activity have not been analyzed.
An orally administered hop extract and subcutaneously injected XH were administered to Sprague-Dawley rats over 4 days. LC-MS-MS analysis of plasma, liver, and mammary gland revealed that XH accumulated in liver and mammary glands. Compared with the low level in the original extract, 8-prenylnaringenin was enriched in the tissues. Hops and XH-induced NQO1 in the liver, while only hops reduced NQO1 activity in the mammary gland. Mechanistic studies revealed that hops modulated NQO1 through three mechanisms. In liver cells, (i) XH modified Kelch-like ECH-associated protein leading to nuclear factor (erythroid-derived 2)-like 2 (Nrf2) translocation and antioxidant response element (ARE) activation; (ii) hop-mediated ARE induction was partially mediated through phosphorylation of Nrf2 by PKC; (iii) in breast cells, 8-prenylnaringenin reduced NQO1 likely through binding to estrogen receptorα, recruiting Nrf2, and downregulating ARE-regulated genes.
XH and 8-prenylnaringenin in dietary hops are bioavailable to the target tissues. While hops and XH might be cytoprotective in the liver, 8-prenylnaringenin seems responsible for hop-mediated NQO1 reduction in the mammary gland.
啤酒花含有植物雌激素 8- prenylnaringenin 和细胞保护化合物黄腐酚 (XH)。XH 在体外诱导解毒酶 NAD(P)H-醌氧化还原酶 (NQO1)；然而，XH 和 8- prenylnaringenin 的组织分布及其组织特异性活性尚未被分析。
在 4 天内，通过口服啤酒花提取物和皮下注射 XH 向 Sprague-Dawley 大鼠给药。对血浆、肝脏和乳腺组织的 LC-MS-MS 分析表明，XH 积聚在肝脏和乳腺中。与原始提取物中的低水平相比，8- prenylnaringenin 在组织中丰富。啤酒花和 XH 诱导肝脏中的 NQO1，而只有啤酒花降低了乳腺中的 NQO1 活性。机制研究表明，啤酒花通过三种机制调节 NQO1。在肝细胞中，(i) XH 修饰 Kelch-like ECH-associated protein 导致核因子 (erythroid-derived 2)-like 2 (Nrf2) 易位和抗氧化反应元件 (ARE) 激活；(ii) 啤酒花介导的 ARE 诱导部分通过 PKC 对 Nrf2 的磷酸化介导；(iii) 在乳腺细胞中，8- prenylnaringenin 可能通过与雌激素受体α结合、募集 Nrf2 和下调 ARE 调节基因来降低 NQO1。
膳食啤酒花中的 XH 和 8- prenylnaringenin 可被靶组织吸收。虽然啤酒花和 XH 可能在肝脏中具有细胞保护作用，但 8- prenylnaringenin 似乎是啤酒花介导的 NQO1 降低在乳腺中的原因。
