A first step in the quest for the active constituents in Filipendula ulmaria (meadowsweet): comprehensive secondary metabolite identification by liquid chromatography-quadrupole orbitrap mass spectrometry

Many natural products are pro-drugs that are metabolized and activated after oral administration. Nevertheless this aspect is usually overlooked when searching for new lead compounds for therapeutic agents. This study is part of a project that aims to identify new leads by fast metabolic profiling of plant extracts before and after treatment with a human gastrointestinal metabolization model. Pharmacological and chromatographic/phytochemical data of extracts and metabolized extracts will be analyzed in a metabolomics approach in order to characterize the active constituents.

In this project Filipendula ulmaria (meadowsweet) has been selected as case study for the characterization of new leads for anti-inflammatory drugs. Previous studies have shown that meadowsweet extracts contain phenolic constituents such as flavonoids (glycosides and aglycons), tannins and salicyl derivatives, as well as a limited number of non-phenolic constituents (e.g. triterpenes, carotenoids). In view of the phenolic nature of the main reported constituents, extensive metabolisation after oral intake before absorption can be expected. Salicylic acid, the in vivo metabolite of salicylic alcohol derivatives has been described as being responsible for part of the pharmacological activity, but there is increasing evidence that other constituents contribute as well.

The current study presents a comprehensive identification of secondary metabolites in meadowsweet by liquid chromatography-photodiode array detection-accurate mass mass spectrometry as a first step in the search for its active constituents. Several sample preparation protocols were compared to optimize a comprehensive extraction method that covers the full range of constituents. Next to salicyl derivatives, many other compounds were detected in meadowsweet that may contribute to its health benefits: a large variety of phenolic derivatives were tentatively identified, many of which have not been identified in meadowsweet before.