Pycnogenol inhibits tumor necrosis factor-alpha-induced nuclear factor kappa B activation and adhesion molecule expression in human vascular endothelial cells

The transcriptional regulatory protein nuclear factor kappa B (NF-kappa B) participates in the control of gene expression of many modulators of inflam matory and immune responses, including vascular cell adhesion molecule-1 (V CAM-1) and intercellular adhesion molecule-1 (ICAM-1). The heightened expre s sion of these adhesion molecules has been reported to play a critical rol e in atherosclerosis, inflammation, ischemic vascular disorders, diabetes, and cancer metastasis. In the present study, we investigated the effect of pycnogenol, an antioxidant phytochemical, on the activation of NF-kappa B a nd the induction of VCAM-1 and ICAM-1 in tumor necrosis factor (TNF)-alpha- treated human umbilical vein endothelial cells (HUVECs). Gel-shift analysis of HUVEC demonstrated that pretreatment with pycnogenol exhibited a concen tration-dependent suppression of TNF-alpha-induced activation of NF-kappa B . Induction of VCAM-1 and ICAM-1 surface expression by TNF-alpha was dose-d ependently reduced by pycnogenol. TNF-alpha significantly increased the rel ease of superoxide anion and hydrogen peroxide from HUVECs. Pycnogenol dose -dependently inhibited their release. The ability of pycnogenol to inhibit NF-kappa B activation and VCAM-1 and ICAM-1 expression suggests that this p hytochemical may play an important role in halting or preventing the athero genic process.