Morroniside Derivative Regulates E-Selectin Expression in Human Endothelial Cells

Abstract

E-selectin is particularly of interest in the case of inflammatory diseases owing to its expression in the activated endothelium. E-selectin mediates cell tethering and rolling interactions through the recognition of sialofucosylated lewis carbohydrates expressed on circulating leukocytes. This phenomenon serves as an important trigger in inflammatory response. We prepared three morroniside derivatives and harpagoside as a positive control and then examined the effects of these compounds on E-selectin expression in human endothelial cell cultures. We found that 7-O-cinnamoylmorroniside significantly suppressed the expression of E-selectin induced with TNF-α (IC₅₀ = 49.3 μM). Furthermore, it was more active than another cinnamic-acid-conjugated iridoid glycoside (harpagoside; IC₅₀ = 88.2 μM), 7-O-methylmorroniside, and morroniside itself. These results ­suggest that 7-O-cinnamoylmorroniside is a potent inhibitor of TNF-α-induced E-selectin expression and that it may be useful as an anti-inflammatory agent.