Water avens (Geum rivale) and Skin irritation: evidence and sources

Plants used in Swedish traditional medicine to treat inflammatory diseases and/or wounds were selected, based on literature data, for evaluation of inhibitory activity on prostaglandin biosynthesis and platelet activating factor (PAF)-induced exocytosis in vitro. Fifty-nine water extracts from 52 different plants in 28 families were tested. A number of plants, e.g. Calluna vulgaris, Corylus avellana, Geum urbanum, Juniperus communis, Polygonum aviculare, Potentilla erecta and Salix caprea were found to be active in both assays. The most potent cyclooxygenase inhibitors were extracts of Calluna vulgaris, Potentilla erecta and Salix caprea. None of the extracts inhibited just the prostaglandin biosynthesis. In the PAF-test, high inhibition was obtained by 19 extracts, the most potent of which were from Geum rivale, G. urbanum, Solanum dulcamara, Symphytum x uplandicum and Vaccinium vitis-idaea. The in vitro effects in relation to the traditional use, chemical contents and botanical classification, as well as the possibilities and the limitations of the methods are discussed.

Ethnopharmacological relevance Ellagitannin-rich plant materials are widely used in traditional medicine as effective, internally used anti-inflammatory agents. Due to the not well-established bioavailability of ellagitannins, the mechanisms of observed therapeutic effects following oral administration still remain unclear. The aim of the study was to evaluate if selected ellagitannin-rich plant materials could be the source of bioavailable gut microbiota metabolites, i.e. urolithins, together with determination of the anti-inflammatory activity of the metabolites produced on the THP-1 cell line derived macrophages model. Materials and methods The formation of urolithins was determined by ex vivo incubation of human fecal samples with aqueous extracts from selected plant materials. The anti-inflammatory activity study of metabolites was determined on PMA differentiated, IFN-γ and LPS stimulated, human THP-1 cell line-derived macrophages. Results The formation of urolithin A, B and C by human gut microbiota was established for aqueous extracts from Filipendula ulmaria (L.) Maxim. herb (Ph. Eur.), Geranium pratense L. herb, Geranium robertianum L. herb, Geum urbanum L. root and rhizome, Lythrum salicaria L. herb (Ph. Eur.), Potentilla anserina L. herb, Potentilla erecta (L.) Raeusch rhizome (Ph. Eur.), Quercus robur L. bark (Ph. Eur.), Rubus idaeus L. leaf, Rubus fruticosus L. and pure ellagitannin vescalagin. Significant inhibition of TNF-α production was determined for all urolithins, while for the most potent urolithin A inhibition was observed at nanomolar concentrations (at 0.625 μM 29.2±6.4% of inhibition). Urolithin C was the only compound inhibiting IL-6 production (at 0.625 μM 13.9±2.2% of inhibition). Conclusions The data obtained clearly indicate that in the case of peroral use of the examined ellagitannin-rich plant materials the bioactivity of gut microbiota metabolites, i.e. urolithins, has to be taken under consideration.

Water avens ( Geum rivale L.) is a common Rosaceae plant widely spread in Europe and North America. It is rich in biologically active natural products, some of which are promising as prospective pharmaceuticals. The extracts of water avens are well known for their triterpenoid metabolites and associated anti-inflammatory, antimicrobial and antioxidant activities. However, the polyphenolic profiles of G. rivale L. are still awaiting complete characterization. Accordingly, the contribution of its individual components to the antioxidant, antibacterial and neuroprotective activity of the extracts is still unknown. As this plant can be available on an industrial scale, a better knowledge of its properly-relevant constituents might give access to new highly-efficient pharmaceutical substances and functional products. Therefore, herein we comprehensively characterize the secondary metabolome of G. rivale by ESI-HR-MS, ESI-HR-MS n and NMR spectroscopy with a special emphasis on the polyphenolic composition of its aerial parts. Furthermore, a multilateral evaluation of the antioxidant, neuroprotective and antibacterial properties of the aqueous and ethyl acetate fractions of the total aqueous alcoholic extract as well as individual isolated polyphenols was accomplished. Altogether four phenolic acid derivatives (trigalloyl hexose, caffeoyl-hexoside malate, ellagic acid and ellagic acid pentoside), six flavonoids (three quercetin derivatives, kaempferol and three its derivatives and two isorhamnetin derivatives) and four tannins (HHDP-hexoside, proantocyanidin dimer, pedunculagin I and galloyl-bis-HHDP-hexose) were identified in this plant for the first time. The obtained aqueous and ethyl acetate fractions of the total extract as well as the isolated individual compounds showed pronounced antioxidant activity. In addition, a pronounced antibacterial activity against several strains was proved for the studied fractions (for ethyl acetate fraction the highest activity against E. coli АТСС 25922 and S. aureus strains ATCC 27853 and SG-511 (MIC 15.6 μg/mL) was observed; for aqueous fraction-against Staphylococcus aureus SG-511 (MIC 31.2 μg/mL)). However, the anti-neurodegenerative (neuroprotective) properties could not be found with the employed methods. However, the antibacterial activity of the fractions could not be associated with any of the isolated individual major phenolics (excepting 3- O -methylellagic acid). Thus, the aerial parts of water avens represent a promising source of polyphenolic compounds with antioxidant activity and therefrom derived human health benefits, although the single constituents isolated so far lack a dominant selectively bioactive constituent in the bioassays performed.

From 42 Rosaceae species, only the Rosoideae species exhibit high tannin content and elastase inhibiting activity such as Filipendula ulmaria, Geum montanum, G. rivale, Alchemilla xanthochlora and Sanguisorba minor. Other studied species from Spiraeoideae, Maloideae and Prunoideae subfamilies are less rich in tannin and also less active.