Pinosylvin induces cell survival, migration and anti-adhesiveness of endothelial cells via nitric oxide production.

Pinosylvin is a phenolic compound mainly found in the Pinus species. To determine the vascular functions of pinosylvin, we first examined both proliferation and apoptosis of bovine aortic endothelial cells (BAECs) in the presence of pinosylvin. When BAECs were treated with pinosylvin, etoposide- or starvation-induced apoptosis was shown to be significantly reduced. The anti-apoptotic effect of pinosylvin was mediated by inhibition of caspase-3. Moreover, pinosylvin was shown to activate endothelial nitric oxide synthetase (eNOS). At 1 pM, pinosylvin appeared to have a cell-proliferative effect in the endothelial cell. The pinosylvin-induced cell proliferation was declined by treatment with L-NAME, an eNOS inhibitor. Then, we found that pinosylvin had a stimulatory effect on cell migration and tube formation. These stimulatory effects suggest that pinosylvin is likely to act as a pro-angiogenic factor. Yet another effect of pinosylvin was inhibition of lipopolysaccharide-induced THP-1 cell adhesion to endothelial cells. Altogether, we propose that pinosylvin may be utilized as a phytotherapic agent for the prevention of cardiovascular inflammatory diseases.