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黄腐酚经口摄入可减轻人 PBMCs 中脂磷壁酸诱导的炎症反应。

Oral intake of xanthohumol attenuates lipoteichoic acid-induced inflammatory response in human PBMCs.

机构信息

Department of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, Josef-Holaubek-Platz 2 (UZA II), 1090, Vienna, Austria.

Department of Pharmaceutical Sciences, Division of Pharmacognosy, University of Vienna, Josef-Holaubek-Platz 2, 1090, Vienna, Austria.

出版信息

Eur J Nutr. 2022 Dec;61(8):4155-4166. doi: 10.1007/s00394-022-02964-2. Epub 2022 Jul 20.

Abstract

PURPOSE

The aim of the study was to determine if xanthohumol, a prenylated chalcone found in Hop (Humulus lupulus), has anti-inflammatory effects in healthy humans if applied in low doses achievable through dietary intake.

METHODS

In a placebo-controlled single-blinded cross-over design study, 14 healthy young men and women either consumed a beverage containing 0.125 mg xanthohumol or a placebo. Peripheral blood mononuclear cells (PBMCs) were isolated before and 1 h after the intake of the beverages. Subsequently, PBMCs were stimulated with or without lipoteichoic acid (LTA) for 24 and 48 h. Concentrations of interleukin-1β (IL-1β), interleukin-6 (IL-6) and soluble cluster of differentiation (sCD14) protein were determined in cell culture supernatant. Furthermore, hTLR2 transfected HEK293 cells were stimulated with LTA in the presence or absence of xanthohumol and sCD14.

RESULTS

The stimulation of PBMCs with LTA for 24 and 48 h resulted in a significant induction of IL-1β, IL-6, and sCD14 protein release in PBMCs of both, fasted subjects and subjects after the ingestion of the placebo. In contrast, after ingesting xanthohumol, LTA-dependent induction of IL-1β, IL-6, and sCD14 protein release from PBMCs was not significantly higher than in unstimulated cells after 48 h. In hTLR2 transfected HEK293 cells xanthohumol significantly suppressed the LTA-dependent activation of cells, an effect attenuated when cells were co-incubated with sCD14.

CONCLUSION

The results of our study suggest that an ingestion of low doses of xanthohumol can suppress the LTA-dependent stimulation of PBMCs through mechanisms involving the interaction of CD14 with TLR2. Study registered at ClinicalTrials.gov (NCT04847193, 22.03.2022).

摘要

目的

本研究旨在确定黄腐酚(一种存在于啤酒花中的类异戊二烯查尔酮)在低剂量下(通过饮食摄入)是否具有抗炎作用,如果应用于健康人群中。

方法

在一项安慰剂对照、单盲交叉设计的研究中,14 名健康的年轻男性和女性饮用含有 0.125mg 黄腐酚的饮料或安慰剂。在摄入饮料前后分离外周血单核细胞(PBMC)。随后,将 PBMC 用或不用脂磷壁酸(LTA)刺激 24 和 48 小时。在细胞培养上清液中测定白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和可溶性 CD14 蛋白的浓度。此外,用 LTA 刺激转染 hTLR2 的 HEK293 细胞,并在存在或不存在黄腐酚的情况下刺激 sCD14。

结果

用 LTA 刺激 PBMC 24 和 48 小时,禁食组和安慰剂组 PBMC 中 IL-1β、IL-6 和 sCD14 蛋白的释放均显著增加。相比之下,在摄入黄腐酚后,48 小时时,LTA 依赖性诱导的 PBMC 中 IL-1β、IL-6 和 sCD14 蛋白的释放与未刺激细胞相比并不显著升高。在转染 hTLR2 的 HEK293 细胞中,黄腐酚显著抑制了 LTA 依赖性的细胞激活,当细胞与 sCD14 共孵育时,这种抑制作用减弱。

结论

我们的研究结果表明,低剂量摄入黄腐酚可通过涉及 CD14 与 TLR2 相互作用的机制抑制 LTA 依赖性的 PBMC 刺激。该研究在 ClinicalTrials.gov 注册(NCT04847193,2022 年 3 月 22 日)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8a3/9596557/f4a2e2586bb3/394_2022_2964_Fig1_HTML.jpg

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