Alte Drogen – neue Erkenntnisse? Neue Strategien zur adjuvanten Behandlung von Harnwegsinfekten mit Schachtelhalmkraut^[*]

ZUSAMMENFASSUNG

Tamm-Horsfall-Protein (syn. THP, Uromodulin) ist ein im distalen Tubulus der Niere sekretiertes Protein, welches in der Lage ist, uropathogene E. coli zu binden und somit deren Ausscheidung zu verbessern und die Pathogen-Wirt-Interaktion zu reduzieren. Die Erhöhung der Sekretion von THP durch spezielle Induktoren stellt eine neue und innovative Therapiestrategie zur Prophylaxe und/oder Behandlung von Harnwegsinfekten dar.

In einer biomedizinischen Studie mit n=10 Probanden wurde der Einfluss eines Schachtelhalmkraut-Trockenextraktes (DEV 4–7:1, Auszugsmittel Wasser) aus Equisetum arvense L. nach siebentägiger Einnahme auf die THP-Sekretion untersucht. Die jeweilige Tagesdosis des Extraktes (1,30 g) entspricht 7,2 g Droge und somit der Dosierungsempfehlung des HMPC. Die Quantifizierung der THP-Konzentrationen in den Einzelproben und in gepooltem Urin erfolgte aus den an den Studientagen 0, 3, 6 und 8 gesammelten morgendlichen Mittelstrahlurinen mittels validiertem ELISA. Zusätzlich wurden die Elektrolyte in allen Urinproben sowie der Kreatinin-Gehalt quantifiziert. Routineparameter wurden mittels Urinteststreifen bestimmt.

Das THP/Kreatinin [µg/mg]-Verhältnis (= THP-Ausscheidungsrate) unter der Anwendung von Schachtelhalmextrakt zeigte signifikante Steigerungen über die jeweilige Anwendungsdauer (bis zu 400%, bezogen auf den Ausgangswert des Tag-0-Urins). Ebenfalls zeigte sich eine diuretische Wirkung, die über die erniedrigte Osmolarität und die erhöhte Elektrolytausscheidung (Na⁺, Cl^–, Ca²⁺ sowie Silicium-Derivate) erkennbar war. Weiterhin wurde der Einfluss der Urinproben im ex-vivo-Assay auf die Adhäsion von UPEC (Stamm NU14) auf humane T24-Blasenzellen untersucht. Dabei zeigte sich, dass die relative bakterielle Adhäsion an die Wirtszellen im Laufe der Schachtelhalmbehandlung signifikant abnahm. Die Hemmung der bakteriellen Adhäsion korreliert sehr gut mit der THP-Zunahme in den jeweiligen Urinproben. Der über LC-MS vollständig charakterisierte Schachtelhalmextrakt zeigte selbst keine anti-adhäsiven Eigenschaften, sodass daraus zurückgeschlossen werden kann, dass entweder die renale Stimulation von THP oder die induzierte Diurese zu einer Verringerung der bakteriellen Adhäsion führt. Die vorliegenden Untersuchungen könnten dazu dienen, die traditionelle Verwendung von Ackerschachtelhalm bei unkomplizierten Harnwegsinfektionen zu rationalisieren.

Abstract

Tamm-Horsfall protein (syn. THP, Uromodulin) is a protein secreted in the distal tubule of the kidney, which is able to bind uropathogenic E. coli and thus improves the bacterial excretion and reduces the pathogen-host interaction. Increasing the secretion of THP by specific inducers represents a novel and innovative therapeutic strategy for the prophylaxis and/or treatment of urinary tract infections.

In a biomedical study with n=10 subjects the influence of a dry extract of horsetail herb (herb extract ration 4–7:1, solvent water) from Equisetum arvense L. on THP secretion was investigated after seven days of oral ingestion. The respective daily dose of the extract (1.30 g) corresponds to 7.2 g of the herbal drug material and thus to the dosage recommendation of the HMPC. Quantification of THP concentrations in individual samples and pooled urine were performed from morning midstream urines, collected on study days 0, 3, 6, and 8, using validated ELISA. In addition, electrolytes in all urine samples and creatinine levels were quantified. Routine parameters were determined by urine test strips.

The THP/creatinine [µg/mg] ratio (= THP excretion rate) under application of horsetail extract showed significant increases over the respective application periods (up to 400%, relative to the baseline day 0 urine value). A diuretic effect was evident by decreased osmolarity and increased electrolyte excretion (Na⁺, Cl^–, Ca²⁺, also Silicon derivatives). Furthermore, the influence of the urine samples within a specific flow cytometric ex vivo assay on the adhesion of fluorescent-labelled UPEC (strain NU14) to human T24 bladder cells was investigated. The data indicated that the relative bacterial adhesion to host cells decreased significantly during the course of horsetail treatment. The inhibition of bacterial adhesion correlated well with the THP increase in the respective urine samples. The horsetail extract itself, fully characterized by LC-MS, did not show any anti-adhesive properties, so it can be concluded that either renal stimulation of THP or induced diuresis explains a decrease in bacterial adhesion. The present studies may serve to rationalize the traditional use of horsetail herb in uncomplicated urinary tract infections.

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