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Planta Med
DOI: 10.1055/a-2563-7503
Original Papers

Complex Standard Formulation as an Example for Synergism and Improved Antibacterial Activity Against Uropathogenic Escherichia coli for Urinary Tract Infections

Steffen Boertz
1   Institute of Pharmaceutical Biology and Phytochemistry, University of Münster, Germany
,
Madhubani Dey
2   Institute of Hygiene, University of Münster, Germany
,
Fabian Herrmann
1   Institute of Pharmaceutical Biology and Phytochemistry, University of Münster, Germany
,
Stefan Esch
1   Institute of Pharmaceutical Biology and Phytochemistry, University of Münster, Germany
,
Jandirk Sendker
1   Institute of Pharmaceutical Biology and Phytochemistry, University of Münster, Germany
,
Ulrich Dobrindt
2   Institute of Hygiene, University of Münster, Germany
,
Andreas Hensel 
1   Institute of Pharmaceutical Biology and Phytochemistry, University of Münster, Germany
› Author AffiliationsFinancial support by the Wilhelm Doerenkamp Foundation, Switzerland, to AH and UD is acknowledged. The study was carried out within the Graduate School of National Products GS-NP.
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Abstract

For the treatment of urinary tract infections, mixtures of different herbal materials are frequently used within traditional clinical practice. A complex formulation, widely used in Germany for the preparation of aqueous extracts with Betula sp., Agropyron repens, Solidago gigantea, and Ononis spinosa, was infused as a mixture from all four components (combined extract). In addition, the four herbs were extracted separately, and the extracts were mixed subsequently (separate extract). None of the extracts influenced the proliferation of UPEC-UTI89 and the cell viability of T24 bladder cells. The combined extract significantly reduced the activity of type-1 fimbriae of UPEC CFT073. This effect was not observed for the mixture of the separately extracted herbs. Systematic investigation of the combined extract and binary mixtures by LC-MS and bioassays indicated that a series of malonylated dammarane triterpenes from Betula spp. leaves was extracted in the presence of Solidago sp. These dammaranes are responsible for the antiadhesive effect. The combined extract of Betula sp. and Solidago gigantea BSC, as well as a dammarane-enhanced fraction (DEF), showed significant antiadhesive effects in a 2D-adhesion assay, as well as in three-dimensional RT4- bladder cell spheroids. RT-qPCR of UTI89 incubated with DEF indicated downregulation of fimC, fimD, and fimH with impact on the chaperone-usher system and correct pili formation. Increased expression of the motility gene fliC indicates a switch from a static to a motile lifestyle. The S-fimbrial gene sfaG was significantly downregulated, but this did not result in phenotypic changes. Based on an improved extraction of birch leaf constituents, the data rationalize the importance of combinations of herbal drugs.

Keywords

Adhesion - Betula pendula - Betulaceae - chaperon-usher - dammarane - invasion - Solidago gigantea - Asteraceae - spheroid - synergism - uropathogenic E. coli

Supporting Information

    Table 1S indicates the composition of kidney-bladder tea preparations I to VII, according to the German governmental exempt standard formulations. Figure 1S shows the influence of the different extracts ComE, SepE, AWE, BWE, OWE, and SWE on cell viability of T24 bladder cells after 48 h incubation time, and Figure 2S indicates the influence of these extracts on the proliferation of UPEC. Figure 3S indicates the effect of DEF on hemagglutination of bovine erythrocytes on S-fimbriae dominated E. coli IHE3034.

  • Supporting Information


Publication History

Received: 24 October 2024

Accepted after revision: 20 March 2025

Accepted Manuscript online:
20 March 2025

Article published online:
03 April 2025

© 2025. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

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