Ursolic acid and oleanolic acid, members of pentacyclic triterpenoid acids, suppress TNF-α-induced E-selectin expression by cultured umbilical vein endothelial cells.

E-selectin is an early response adhesion molecule expressed on the surface of endothelial cells during inflammatory responses. We examined the effects of two pentacyclic triterpenoid acids, ursolic acid (UA) and oleanolic acid (OA), on the expression of E-selectin by cultured human umbilical vein endothelial cells (HUVECs). Treatment of the cells with UA or OA alone did not influence expression of E-selectin. Expression of E-selectin mRNA and surface antigen by HUVECs was induced by treatment with tumor necrosis factor-α (TNF-α) in a dose- and time-dependent manner. TNF-α-induced up-regulation of E-selectin was abrogated by pre-treatment of the cells with UA or OA which decreased expression of E-selectin mRNA. The repression of E-selectin mRNA expression caused by the pentacyclic triterpenoid acids paralleled the inhibition of NF-κB activation and nuclear translocation, as evaluated by electrophoretic mobility shift assays, although the degree of repression by UA was approximately two times more effective than that of OA. The results suggest that UA and OA suppress the inflammatory cytokine-induced expression of E-selectin in endothelial cells by decreasing E-selectin transcription via inhibition of NF-κB activation. Thus, UA and OA function as anti-inflammatory agents. The differences in the inhibitory efficacy between UA and OA may be due to conformational differences in ring-E of the two pentacyclic triterpenoid acids.