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

Abstract

The transcriptional regulatory protein nuclear factor kappa B (NF-kappa B) participates in the control of gene expression of many modulators of inflammatory and immune responses, including vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). The heightened expression of these adhesion molecules has been reported to play a critical role 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 and 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 concentration-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-dependently reduced by pycnogenol. TNF-alpha significantly increased the release 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 phytochemical may play an important role in halting or preventing the atherogenic process.

Suppressive Effects of Genistein on Oxidative Stress and NFκB Activation in RAW 264.7 Macrophages

“…The lower band could represent inactivated NFkB bound with IB or the monomeric p52 component of NFkB. 35) Incubation of genistein at 20-100 mM with cells did not show inhibitive eŠect on NFkB activity in dose-dependent manner. Genistein at 50 mM and 100 mM inhibited the activation of NFkB induced by LPS signiˆcantly (Fig.…”

Pycnogenol, an extract from French maritime pine, suppresses Toll-like receptor 4-mediated expression of adipose differentiation-related protein in macrophages

“…PYC is a mixture of phenols, polyphenols, taxifolin, and condensed flavonoids (40), and it is known that it has a strong antioxidant effect (38). Nowadays, PYC is widely used in general populations as a dietary supplement beneficial for various conditions despite the lack of sufficient knowledge about the molecular basis of its action.…”

TLR4 signaling induces TLR2 expression in endothelial cells via neutrophil NADPH oxidase

“…NF-κB signaling occurs via an oxidant-sensitive pathway (21)(22)(23)(24)(25). Our previous studies showed that the endothelial cell is a key target of PMN NADPH oxidase activity (26 Interactions of polymorphonuclear neutrophils (PMNs) with endothelial cells may contribute to the activation of endothelial cell responses involved in innate immunity.…”