Department of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, Josef-Holaubek Platz 2, 1090 Vienna, Austria.
Department of Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
Int J Mol Sci. 2022 Oct 21;23(20):12702. doi: 10.3390/ijms232012702.
Infections with Gram-negative bacteria are still among the leading causes of infection-related deaths. Several studies suggest that the chalcone xanthohumol (XN) found in hop (Humulus lupulus) possesses anti-inflammatory effects. In a single-blinded, placebo controlled randomized cross-over design study we assessed if the oral intake of a single low dose of 0.125 mg of a XN derived through a XN-rich hop extract (75% XN) affects lipopolysaccharide (LPS)-induced immune responses in peripheral blood mononuclear cells (PBMCs) ex vivo in normal weight healthy women ( = 9) (clinicaltrials.gov: NCT04847193) and determined associated molecular mechanisms. LPS-stimulation of PBMCs isolated from participants 1 h after the intake of the placebo for 2 h resulted in a significant induction of pro-inflammatory cytokine release which was significantly attenuated when participants had consumed XN. The XN-dependent attenuation of proinflammatory cytokine release was less pronounced 6 h after the LPS stimulation while the release of sCD14 was significantly reduced at this timepoint. The LPS-dependent activation of hTLR4 transfected HEK293 cells was significantly and dose-dependently suppressed by the XN-rich hop extract which was attenuated when cells were co-challenged with sCD14. Taken together, our results suggest even a one-time intake of low doses of XN consumed in a XN-rich hop extract can suppress LPS-dependent stimulation of PBMCs and that this is related to the interaction of the hop compound with the CD14/TLR4 signaling cascade.
革兰氏阴性菌感染仍然是感染相关死亡的主要原因之一。有几项研究表明，啤酒花（Humulus lupulus）中发现的查尔酮黄腐酚（XN）具有抗炎作用。在一项单盲、安慰剂对照、随机交叉设计的研究中，我们评估了口服低剂量 0.125 毫克 XN 富啤酒花提取物（75%XN）是否会影响正常体重健康女性（=9）外周血单个核细胞（PBMC）中脂多糖（LPS）诱导的免疫反应（clinicaltrials.gov：NCT04847193），并确定了相关的分子机制。在参与者口服安慰剂 1 小时后，XN 对 PBMC 的刺激持续 2 小时，导致促炎细胞因子释放显著增加，而当参与者摄入 XN 时，这种增加显著减弱。XN 依赖性促炎细胞因子释放的减弱在 LPS 刺激后 6 小时不太明显，而此时 sCD14 的释放显著减少。XN 富啤酒花提取物对 hTLR4 转染的 HEK293 细胞的 LPS 依赖性激活具有显著的、剂量依赖性的抑制作用，当细胞与 sCD14 共同受到挑战时，这种抑制作用会减弱。综上所述，我们的研究结果表明，即使是单次摄入低剂量的 XN 也能抑制 LPS 对 PBMC 的刺激，这与啤酒花化合物与 CD14/TLR4 信号级联的相互作用有关。
