Institute of Biochemistry (Emil-Fischer Zentrum), Friedrich-Alexander University Erlangen-Nürnberg, Fahrstr. 17, D-91054 Erlangen, Germany.
Institute of Nutritional Sciences, University of Hohenheim, Garbenstr. 28, D-70599 Stuttgart, Germany.
Cells. 2019 Apr 17;8(4):359. doi: 10.3390/cells8040359.
Xanthohumol (XN), a prenylated chalcone from hops, has been reported to exhibit a variety of health-beneficial effects. However, poor bioavailability may limit its application in the prevention and therapy of diseases. The objective of this study was to determine whether a micellar solubilization of xanthohumol could enhance the bioavailability and biological efficacy of xanthohumol in a Western-type diet (WTD) induced model of obesity, diabetes and non-alcoholic fatty liver disease (NAFLD). After 3 weeks feeding with WTD, XN was additionally applied per oral gavage as micellar solubilizate (s-XN) or native extract (n-XN) at a daily dose of 2.5 mg/kg body weight for a further 8 weeks. Control mice received vehicle only in addition to the WTD. WTD-induced body weight-gain and glucose intolerance were significantly inhibited by s-XN application. Furthermore, WTD-induced hepatic steatosis, pro-inflammatory gene expression (MCP-1 and CXCL1) and immune cell infiltration as well as activation of hepatic stellate cells (HSC) and expression of collagen alpha I were significantly reduced in the livers of s-XN-treated mice compared to WTD controls. In contrast, application of n-XN had no or only slight effects on the WTD-induced pathological effects. In line with this, plasma XN concentration ranged between 100-330 nmol/L in the s-XN group while XN was not detectable in the serum samples of n-XN-treated mice. In conclusion, micellar solubilization enhanced the bioavailability and beneficial effects of xanthohumol on different components of the metabolic syndrome including all pathological steps of NAFLD. Notably, this was achieved in a dose more than 10-fold lower than effective beneficial doses of native xanthohumol reported in previous in vivo studies.
黄腐酚（XN）是一种来自啤酒花的类查尔酮，据报道具有多种有益健康的作用。然而，其生物利用度较差可能限制了其在疾病预防和治疗中的应用。本研究旨在确定黄腐酚胶束增溶是否能提高黄腐酚在西方饮食（WTD）诱导的肥胖、糖尿病和非酒精性脂肪性肝病（NAFLD）模型中的生物利用度和生物功效。在 WTD 喂养 3 周后，XN 以胶束增溶物（s-XN）或天然提取物（n-XN）的形式通过口服灌胃另外给予每日 2.5 毫克/千克体重剂量，进一步持续 8 周。对照组小鼠除 WTD 外还给予载体。s-XN 应用显著抑制 WTD 诱导的体重增加和葡萄糖不耐受。此外，与 WTD 对照组相比，s-XN 处理小鼠的肝脏中 WTD 诱导的肝脂肪变性、促炎基因表达（MCP-1 和 CXCL1）和免疫细胞浸润以及肝星状细胞（HSC）激活和胶原 alpha I 表达均显著减少。相比之下，n-XN 的应用对 WTD 诱导的病理影响没有或只有轻微影响。与此一致，s-XN 组的血浆 XN 浓度在 100-330 纳米摩尔/升之间，而 n-XN 处理小鼠的血清样本中未检测到 XN。总之，胶束增溶提高了黄腐酚对代谢综合征不同成分的生物利用度和有益作用，包括 NAFLD 的所有病理步骤。值得注意的是，这是在比以前体内研究中报道的有效有益剂量低 10 多倍的剂量下实现的。
