Endothelial hyperpermeability followed by edema formation is a hallmark of many severe disorders. Drugs that directly target endothelial barrier function are widely lacking. Extracts from hawthorn (Crataegus sp., Rosaceae) prevent vascular leakage by endothelial barrier-regulating systems in vitro and in vivo, by blocking Ca/PKC/RhoA and activating cAMP/Epac1/Rap1 pathways.

The project aims at identifying the metabolites in the extracts that are responsible for the activities observed in vitro and in vivo. HPLC-based activity profiling is used to rapidly pinpoint to active constituents, and structure elucidation is performed by a combination of on-line and off-line coupled spectrsocopic methods. The project will provide molecular understanding of the clinically proven therapeutic properties of Crataegus extracts, and may provide entry points for new molecules restoring endothelial barrier function.