Investigations were carried out to understand the molecular basis of the effect of ursolic acid on angiogenesis by analysing its effects on the expression of modulators of angiogenesis by HUVECs in culture. Treatment with ursolic acid increased the expression of adhesion molecules such as E-selectin, CD-31 and I-CAM, upregulated angiogenic growth factors such as VEGF and FGF-2 and their receptors and caused increase in the ratio of PGE2 to PGD2. Reversal of the effect of ursolic acid by inhibition of PI3K-Akt pathway and increase in the level of phospho Akt suggest that the ursolic acid effect is mediated through PI3K-Akt pathway. (C) 2008 Elsevier Inc. All rights reserved.