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七天口服马缨丹叶浸剂对尿液中尿路致病性大肠杆菌具有抗粘附的离体活性。

Seven-day Oral Intake of Orthosiphon stamineus Leaves Infusion Exerts Antiadhesive Ex Vivo Activity Against Uropathogenic E. coli in Urine Samples.

机构信息

University of Münster, Institute of Pharmaceutical Biology and Phytochemistry, Münster, Germany.

Pharmacognosy and Phytotherapy, UCL School of Pharmacy, London, United Kingdom.

出版信息

Planta Med. 2023 Jul;89(8):778-789. doi: 10.1055/a-1585-6322. Epub 2021 Sep 14.

Abstract

leaves (Java tea) extract is traditionally used for the treatment of urinary tract infections. According to recent data, animal infection studies, and transcriptomic investigations, polymethoxylated flavones from Java tea exert antiadhesive activity against uropathogenic (UPEC). This antiadhesive activity has been shown to reduce bladder and kidney lesion in a mice infection model. As no data on the antivirulent activity of Java tea intake on humans are available, a biomedical study was performed on 20 healthy volunteers who self-administered infusion (4 × 3 g per day, orally) for 7 days. The herbal material used for the study conformed to the specification of the European Pharmacopoeia, and ultra high-performance liquid chromatography (UHPLC) of the infusion showed rosmarinic acid, caffeic acid, and cichoric acid to be the main compounds aside from polymethoxylated flavones. Rosmarinic acid was quantified in the tea preparations with 243 ± 22 µg/mL, indicating sufficient reproducibility of the preparation of the infusion. Urine samples were obtained during the biomedical study on day 1 (control urine, prior to Java tea intake), 3, 6 and 8. Antiadhesive activity of the urine samples was quantified by flowcytometric assay using pre-treated UPEC NU14 and human T24 bladder cells. Pooled urine samples indicated significant inhibition of bacterial adhesion on day 3, 6 and 8. The urine samples had no influence on the invasion of UPEC into host cells. Bacterial proliferation was slightly reduced after 24 h incubation with the urine samples. Gene expression analysis (qPCR) revealed strong induction of fitness and motility gene and downregulation of hemin uptake system . These data correlate with previously reported datasets from transcriptomic analysis. Increased bacterial motility was monitored using a motility assay in soft agar with UPEC UTI89. The intake of Java tea had no effect on the concentration of Tamm-Horsfall Protein in the urine samples. The present study explains the antiadhesive and anti-infective effect of the plant extract by triggering UPEC from a sessile lifestyle into a motile bacterial form, with reduced adhesive capacity.

摘要

传统上,茶叶(Java 茶)提取物被用于治疗尿路感染。根据最近的数据、动物感染研究和转录组学研究,Java 茶中的多甲氧基黄酮对尿路致病性大肠杆菌(UPEC)具有抗粘附活性。这种抗粘附活性已被证明可减少小鼠感染模型中的膀胱和肾脏损伤。由于没有关于 Java 茶摄入对人类抗病毒活性的可用数据,因此对 20 名健康志愿者进行了一项生物医学研究,这些志愿者自行口服(每天 4×3g)7 天。用于研究的草药材料符合欧洲药典的规定,输液的超高效液相色谱(UHPLC)显示迷迭香酸、咖啡酸和菊苣酸是除多甲氧基黄酮外的主要化合物。茶制剂中的迷迭香酸用 243±22µg/mL 进行定量,表明茶制剂的制备具有足够的重现性。在生物医学研究中,于第 1 天(Java 茶摄入前的对照尿)、第 3、6 和 8 天收集尿液样本。通过使用预处理的 UPEC NU14 和人 T24 膀胱细胞的流式细胞术测定法定量尿液样本的抗粘附活性。第 3、6 和 8 天的混合尿液样本显示出对细菌粘附的显著抑制。尿液样本对 UPEC 侵入宿主细胞没有影响。将尿液样本孵育 24 小时后,细菌增殖略有减少。基因表达分析(qPCR)显示适应性和运动性基因的强烈诱导,以及血红素摄取系统的下调。这些数据与之前从转录组分析报告的数据集相关。使用含有 UPEC UTI89 的软琼脂中的运动测定法监测到细菌运动性增加。Java 茶的摄入对尿液样本中 Tamm-Horsfall 蛋白的浓度没有影响。本研究通过将 UPEC 从静止的生活方式触发为具有降低粘附能力的运动细菌形式,解释了植物提取物的抗粘附和抗感染作用。

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