Scharf Birte, Sendker Jandirk, Dobrindt Ulrich, Hensel Andreas
University of Münster, Institute of Pharmaceutical Biology and Phytochemistry, Münster, Germany.
University Hospital Münster, Institute of Hygiene, Münster, Germany.
Planta Med. 2019 Jan;85(2):126-138. doi: 10.1055/a-0755-7801. Epub 2018 Oct 12.
LC-MS characterized cranberry extract from the fruits of Vaccinium macrocarpon inhibited under in vitro conditions the bacterial adhesion of strain 2980 uropathogenic (UPEC strains UTI89, NU14) to T24 bladder cells and adhesion of UPEC strain CFT073 to A498 kidney cells in a concentration-dependent manner. Within a biomedical study, urine samples from 16 volunteers (8 male, 8 female) consuming cranberry extract for 7 d (900 mg/d) were analyzed for potential antiadhesive activity against UPEC by ex vivo experiments. Results indicated inhibition of adhesion of UPEC strain UTI89 to human T24 bladder cells. Subgroup analysis proved significant inhibition of bacterial adhesion in case of urine samples obtained from male volunteers while female urine did not influence the bacterial attachment. Differences between antiadhesive capacity of urine samples from male/female volunteers were significant. Protein analysis of the urine samples indicated increased amounts of Tamm-Horsfall protein (THP, syn. uromodulin) in the active samples. Inhibition of bacterial adhesion by the urine samples was correlated to the respective amount of THP. As it is known that THP, a highly mannosylated glycoprotein, strongly interacts with FimH of UPEC, this will lead to a decreased interaction with uroplakin, a FimH-binding transmembrane protein of urothelial lining cells. From these data it can be concluded that the antiadhesive effect of cranberry after oral intake is not only related to the direct inhibition of bacterial adhesins by extract compounds but is additionally due to an induction of antiadhesive THP in the kidney.
液相色谱-质谱联用（LC-MS）对蔓越莓提取物进行表征，该提取物取自大果越桔果实，在体外条件下，其对2980型尿路致病性大肠杆菌（UTI89、NU14菌株）与T24膀胱细胞的细菌黏附以及CFT073型尿路致病性大肠杆菌（UPEC）与A498肾细胞的黏附均有浓度依赖性抑制作用。在一项生物医学研究中，通过体外实验分析了16名志愿者（8名男性，8名女性）连续7天（每天900毫克）食用蔓越莓提取物后的尿液样本对尿路致病性大肠杆菌的潜在抗黏附活性。结果表明，该提取物对UTI89型尿路致病性大肠杆菌与人T24膀胱细胞的黏附有抑制作用。亚组分析证明，男性志愿者尿液样本对细菌黏附有显著抑制作用，而女性尿液则不影响细菌黏附。男性/女性志愿者尿液样本的抗黏附能力存在显著差异。尿液样本的蛋白质分析表明，活性样本中Tamm-Horsfall蛋白（THP，即尿调节蛋白）含量增加。尿液样本对细菌黏附的抑制作用与THP的相应含量相关。众所周知，THP是一种高度甘露糖基化的糖蛋白，与尿路致病性大肠杆菌的FimH强烈相互作用，这将导致其与尿路上皮衬里细胞的FimH结合跨膜蛋白尿血小板的相互作用减少。从这些数据可以得出结论，口服蔓越莓后的抗黏附作用不仅与提取物化合物对细菌黏附素的直接抑制有关，还与肾脏中抗黏附性THP的诱导有关。
