Do natural products of plant origin support the therapy of urinary tract infections?
project manager: prof. dr hab. Sebastian Granica;
investigators: dr hab. Jakub Piwowarski, dr Aleksandra Kruk, mgr inż. Dominik Popowski, mgr farm. inż. Karolina Pawłowska
Research project objectives
Urinary tract infections (UTIs) are widespread and affect a large proportion of the human population. The heritage of European traditional medicine is currently in a state of decay. The traditional knowledge about European plants healing properties was eroded by the deep economic and social changes of the past few decades. Many of the medicinal plants being popular for centuries have been superseded by synthetic pharmaceuticals. Such natural products as Ulmariae flos, Urticae folium, Sambuci flos, Orthosiphonis folium, Hernariae herba, Solidaginis herba, Polygoni avicularis herba, Equiseti herba, Betulae folium, Uvae ursi folium, Vitis ideae folium and others were used in Europe since ancient times and are still used in the therapy and prevention of UTIs. Due to incompatibility with drug discovery approaches based on high-throughput screening directed at single molecular target, natural products for the long time were beyond the focus of pharmaceutical companies. The main aim of the project is to find prove or proves justifying the traditional use of plant materials in the prevention and treatment of UTIs caused by E. coli. The project will be focused on comprehensive analysis of chemical composition and gut microbiota metabolism of compounds contained in chosen plant materials. The concept of the role of gut microbiota metabolism and further II phase transformations in the anti-microbial and anti-inflammatory activity of natural products will be investigated.
Research project methodology
In the first part of the current proposal the plant materials traditionally used in the prevention and in the treatment of UTIs will be chosen based on literature research. From each plan material an extract will be prepared and will be phytochemically characterized using modern chromatographic techniques as well as using some standard chemical methods. Next the bioactivity of raw extracts as potential anti-microbial, anti-adhesive and anti-inflammatory agents. The most active raw extracts will be used for the isolation of their active constituents (using column chromatography and prep HPLC). In parallel the gut microbiota metabolism of investigated extracts will be performed. The products of gut microbiota metabolism will be analyzed with UHPLC-DAD-MS method. The mixture of metabolites produced by microbiota will be checked for their antimicrobial, anti-adhesive and antiinflammatory potential. The most active extracts will be used for the analysis of their metabolism and activity using human model. Infusions from chosen plant material/s will be administrated to healthy volunteers. The urine after oral ingestion will be analyzed in order to identify major II phase metabolism products. Samples of urine will be used to check the anti-microbial, antiadhesive and anti-inflammatory activities. Major metabolites found in urine will be isolated if needed. Finally, the hypothesis on the self-killing mechanism of E coli by on site deconjugation of glucuronidated metabolites to active aglycones will be checked in the preliminary patient study. The patients with diagnosed UTI caused by E. coli will be asked to ingest infusion from chosen plant materials. Their urine will be analyzed for the presence of deconjugated metabolites using UHPLC-DAD-MS in comparison to the urine of healthy volunteers.
Expected impact of the research project on the development of science
Obtained results will be used for the verification of major hypothesis put in the current proposal that the usage of extracts from chosen medicinal plant materials is justified in the prevention and the treatment of UTIs. It is expected to significantly expand the knowledge on the mechanism of action of medicinal plant materials in UTIs taking into account their gut microbiota metabolism as well as II phase reactions taking place after absorption and during the elimination of natural products found in ingested extracts. Up to now it is not clear whether medicinal plant materials used by patients in UTIs may have antimicrobial, antiadhesive or anti-inflammatory potential. The role of gut microbiota metabolism of natural products in the context of UTIs remains unresolved and will be addressed within the current proposal.