Linus Pauling Institute, Oregon State University, Corvallis, OR, 97331, USA.
Department of Pharmaceutical Sciences, Oregon State University, Corvallis, OR, 97331, USA.
Sci Rep. 2018 Jan 12;8(1):613. doi: 10.1038/s41598-017-18992-6.
Xanthohumol (XN), a prenylated flavonoid from hops, improves dysfunctional glucose and lipid metabolism in animal models of metabolic syndrome (MetS). However, its metabolic transformation into the estrogenic metabolite, 8-prenylnaringenin (8-PN), poses a potential health concern for its use in humans. To address this concern, we evaluated two hydrogenated derivatives, α,β-dihydro-XN (DXN) and tetrahydro-XN (TXN), which showed negligible affinity for estrogen receptors α and β, and which cannot be metabolically converted into 8-PN. We compared their effects to those of XN by feeding C57BL/6J mice a high-fat diet (HFD) containing XN, DXN, or TXN for 13 weeks. DXN and TXN were present at higher concentrations than XN in plasma, liver and muscle. Mice administered XN, DXN or TXN showed improvements of impaired glucose tolerance compared to the controls. DXN and TXN treatment resulted in a decrease of HOMA-IR and plasma leptin. C2C12 embryonic muscle cells treated with DXN or TXN exhibited higher rates of uncoupled mitochondrial respiration compared to XN and the control. Finally, XN, DXN, or TXN treatment ameliorated HFD-induced deficits in spatial learning and memory. Taken together, DXN and TXN could ameliorate the neurocognitive-metabolic impairments associated with HFD-induced obesity without risk of liver injury and adverse estrogenic effects.
黄腐酚（XN）是一种来自啤酒花的类异戊二烯黄酮，可改善代谢综合征（MetS）动物模型中葡萄糖和脂质代谢功能障碍。然而，其代谢转化为雌激素代谢物 8-异戊烯基柚皮素（8-PN），可能会对其在人类中的应用造成健康隐患。为了解决这个问题，我们评估了两种氢化衍生物，α,β-二氢-XN（DXN）和四氢-XN（TXN），它们对雌激素受体 α 和 β 的亲和力可以忽略不计，并且不能代谢转化为 8-PN。我们通过给 C57BL/6J 小鼠喂食含有 XN、DXN 或 TXN 的高脂肪饮食（HFD）13 周，比较了它们与 XN 的作用。DXN 和 TXN 在血浆、肝脏和肌肉中的浓度均高于 XN。与对照组相比，给予 XN、DXN 或 TXN 的小鼠糖耐量受损得到改善。DXN 和 TXN 治疗导致 HOMA-IR 和血浆瘦素降低。与 XN 和对照组相比，用 DXN 或 TXN 处理的 C2C12 胚胎肌肉细胞表现出更高的解偶联线粒体呼吸率。最后，XN、DXN 或 TXN 治疗改善了 HFD 诱导的空间学习和记忆缺陷。总之，DXN 和 TXN 可改善与 HFD 诱导的肥胖相关的神经认知代谢损伤，而不会引起肝损伤和不良的雌激素作用。
