A novel approach to prevent endothelial hyperpermeability: The Crataegus extract WS® 1442 targets the cAMP/Rap1 pathway

► The Crataegus extract WS® 1442 protects against endothelial hyperpermeability in vivo and in vitro. ► WS® 1442 inhibits detrimental effects of thrombin on adherens junctions, the F-actin cytoskeleton, and the contractile apparatus. ► Mechanistically, WS® 1442 blocks the thrombin-induced barrier-disrupting calcium/PKC/RhoA signaling. ► Concurrently, WS® 1442 activates the barrier-stabilizing cAMP/Epac/Rap1 pathway. ► WS® 1442 opens a novel pharmacological approach to treat hyperpermeability-associated diseases.