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Inhibitory Effect of a French Maritime Pine Bark Extract-Based Nutritional Supplement on TNF-α-Induced Inflammation and Oxidative Stress in Human Coronary Artery Endothelial Cells.

McGrath KC, Li XH, McRobb LS, Heather AK - Evid Based Complement Alternat Med (2015)

Bottom Line: Treatment for 24 hours with HIPER reduced TNF-α-induced reactive oxygen species (ROS) generation that was associated with decreased NADPH oxidase 4 and increased superoxide dismutase-1 expression.HIPER inhibited TNF-α induced monocyte adhesion to HCAECs that was in keeping with decreased expression of vascular cell adhesion molecule-1 and intercellular cell adhesion molecule-1 and decreased nuclear factor-kappa B (NF-κB) activation.Further investigation of mechanism showed HIPER reduced TNF-α induced IκBα and p38 and MEK1/2 MAP kinases phosphorylation.

View Article: PubMed Central - PubMed

Affiliation: Molecular Biosciences Team, School of Life Sciences, University of Technology Sydney, Broadway, NSW, Australia.

ABSTRACT
Oxidative stress and inflammation, leading to endothelial dysfunction, contribute to the pathogenesis of atherosclerosis. The popularity of natural product supplements has increased in recent years, especially those with purported anti-inflammatory and/or antioxidant effects. The efficacy and mechanism of many of these products are not yet well understood. In this study, we tested the antioxidant and anti-inflammatory effects of a supplement, HIPER Health Supplement (HIPER), on cytokine-induced inflammation and oxidative stress in human coronary artery endothelial cells (HCAECs). HIPER is a mixture of French maritime pine bark extract (PBE), honey, aloe vera, and papaya extract. Treatment for 24 hours with HIPER reduced TNF-α-induced reactive oxygen species (ROS) generation that was associated with decreased NADPH oxidase 4 and increased superoxide dismutase-1 expression. HIPER inhibited TNF-α induced monocyte adhesion to HCAECs that was in keeping with decreased expression of vascular cell adhesion molecule-1 and intercellular cell adhesion molecule-1 and decreased nuclear factor-kappa B (NF-κB) activation. Further investigation of mechanism showed HIPER reduced TNF-α induced IκBα and p38 and MEK1/2 MAP kinases phosphorylation. Our findings show that HIPER has potent inhibitory effects on HCAECs inflammatory and oxidative stress responses that may protect against endothelial dysfunction that underlies early atherosclerotic lesion formation.

No MeSH data available.


Related in: MedlinePlus

HIPER reduced NF-κB activation in TNF-α-activated HCAECs. HCAECs were treated with HIPER at a dose of 25 μL/mL for 3 h, before activation with 1 ng/mL TNF-α for 3 h. For (c) additional cells were treated with SB203580 (10 μM) and (d) UO126 (10 μM). For (a) nuclear extract was obtained and NF-κB levels were measured using commercially available NoShift assay. For (b)–(d), cultured cells were used directly in commercially available ELISA kits. Data are shown as mean ± SEM (n = 3) ∗P < 0.05 versus control, #P < 0.05 versus TNF-α.
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fig5: HIPER reduced NF-κB activation in TNF-α-activated HCAECs. HCAECs were treated with HIPER at a dose of 25 μL/mL for 3 h, before activation with 1 ng/mL TNF-α for 3 h. For (c) additional cells were treated with SB203580 (10 μM) and (d) UO126 (10 μM). For (a) nuclear extract was obtained and NF-κB levels were measured using commercially available NoShift assay. For (b)–(d), cultured cells were used directly in commercially available ELISA kits. Data are shown as mean ± SEM (n = 3) ∗P < 0.05 versus control, #P < 0.05 versus TNF-α.

Mentions: Given that HIPER suppressed TNF-α-induced ROS levels and VCAM-1 and ICAM-1 expression, it was next explored whether HIPER suppressed TNF-α-induced NF-κB activation. In its inactivated state, NF-κB is bound by an inhibitor protein, IκBα. In inflammatory conditions, cell signalling cascades that involve MAP kinases lead to the phosphorylation of IκBα [13]. Phosphorylated IκBα is targeted for degradation freeing NF-κB to translocate to the nucleus to active target gene expression that includes VCAM-1 and ICAM-1. Figure 5(a) shows that TNF-α significantly increased NF-κB nuclear activation by 70% (P < 0.05) and that pretreatment of HCAECs with HIPER (25 μL/mL) decreased this effect by 43% (P < 0.05). Figure 5(b) shows that the effect of HIPER on suppressing NF-κB activation was associated with a decrease in phosphorylated IκBα, the inhibitor protein of NF-κB. Phosphorylation of IκBα is driven by MAP kinase activation. Figures 5(c) and 5(d) show that HIPER suppressed p38 and MEK1/2 MAP kinases activation almost to the same basal level as the p38 inhibitor SB203580 or the MEK1/2 inhibitor, UO126. Together, this data suggests that HIPER suppresses the HCAECs inflammatory response, at least in part, via suppression of MAP kinase and NF-κB activation.


Inhibitory Effect of a French Maritime Pine Bark Extract-Based Nutritional Supplement on TNF-α-Induced Inflammation and Oxidative Stress in Human Coronary Artery Endothelial Cells.

McGrath KC, Li XH, McRobb LS, Heather AK - Evid Based Complement Alternat Med (2015)

HIPER reduced NF-κB activation in TNF-α-activated HCAECs. HCAECs were treated with HIPER at a dose of 25 μL/mL for 3 h, before activation with 1 ng/mL TNF-α for 3 h. For (c) additional cells were treated with SB203580 (10 μM) and (d) UO126 (10 μM). For (a) nuclear extract was obtained and NF-κB levels were measured using commercially available NoShift assay. For (b)–(d), cultured cells were used directly in commercially available ELISA kits. Data are shown as mean ± SEM (n = 3) ∗P < 0.05 versus control, #P < 0.05 versus TNF-α.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4664804&req=5

fig5: HIPER reduced NF-κB activation in TNF-α-activated HCAECs. HCAECs were treated with HIPER at a dose of 25 μL/mL for 3 h, before activation with 1 ng/mL TNF-α for 3 h. For (c) additional cells were treated with SB203580 (10 μM) and (d) UO126 (10 μM). For (a) nuclear extract was obtained and NF-κB levels were measured using commercially available NoShift assay. For (b)–(d), cultured cells were used directly in commercially available ELISA kits. Data are shown as mean ± SEM (n = 3) ∗P < 0.05 versus control, #P < 0.05 versus TNF-α.
Mentions: Given that HIPER suppressed TNF-α-induced ROS levels and VCAM-1 and ICAM-1 expression, it was next explored whether HIPER suppressed TNF-α-induced NF-κB activation. In its inactivated state, NF-κB is bound by an inhibitor protein, IκBα. In inflammatory conditions, cell signalling cascades that involve MAP kinases lead to the phosphorylation of IκBα [13]. Phosphorylated IκBα is targeted for degradation freeing NF-κB to translocate to the nucleus to active target gene expression that includes VCAM-1 and ICAM-1. Figure 5(a) shows that TNF-α significantly increased NF-κB nuclear activation by 70% (P < 0.05) and that pretreatment of HCAECs with HIPER (25 μL/mL) decreased this effect by 43% (P < 0.05). Figure 5(b) shows that the effect of HIPER on suppressing NF-κB activation was associated with a decrease in phosphorylated IκBα, the inhibitor protein of NF-κB. Phosphorylation of IκBα is driven by MAP kinase activation. Figures 5(c) and 5(d) show that HIPER suppressed p38 and MEK1/2 MAP kinases activation almost to the same basal level as the p38 inhibitor SB203580 or the MEK1/2 inhibitor, UO126. Together, this data suggests that HIPER suppresses the HCAECs inflammatory response, at least in part, via suppression of MAP kinase and NF-κB activation.

Bottom Line: Treatment for 24 hours with HIPER reduced TNF-α-induced reactive oxygen species (ROS) generation that was associated with decreased NADPH oxidase 4 and increased superoxide dismutase-1 expression.HIPER inhibited TNF-α induced monocyte adhesion to HCAECs that was in keeping with decreased expression of vascular cell adhesion molecule-1 and intercellular cell adhesion molecule-1 and decreased nuclear factor-kappa B (NF-κB) activation.Further investigation of mechanism showed HIPER reduced TNF-α induced IκBα and p38 and MEK1/2 MAP kinases phosphorylation.

View Article: PubMed Central - PubMed

Affiliation: Molecular Biosciences Team, School of Life Sciences, University of Technology Sydney, Broadway, NSW, Australia.

ABSTRACT
Oxidative stress and inflammation, leading to endothelial dysfunction, contribute to the pathogenesis of atherosclerosis. The popularity of natural product supplements has increased in recent years, especially those with purported anti-inflammatory and/or antioxidant effects. The efficacy and mechanism of many of these products are not yet well understood. In this study, we tested the antioxidant and anti-inflammatory effects of a supplement, HIPER Health Supplement (HIPER), on cytokine-induced inflammation and oxidative stress in human coronary artery endothelial cells (HCAECs). HIPER is a mixture of French maritime pine bark extract (PBE), honey, aloe vera, and papaya extract. Treatment for 24 hours with HIPER reduced TNF-α-induced reactive oxygen species (ROS) generation that was associated with decreased NADPH oxidase 4 and increased superoxide dismutase-1 expression. HIPER inhibited TNF-α induced monocyte adhesion to HCAECs that was in keeping with decreased expression of vascular cell adhesion molecule-1 and intercellular cell adhesion molecule-1 and decreased nuclear factor-kappa B (NF-κB) activation. Further investigation of mechanism showed HIPER reduced TNF-α induced IκBα and p38 and MEK1/2 MAP kinases phosphorylation. Our findings show that HIPER has potent inhibitory effects on HCAECs inflammatory and oxidative stress responses that may protect against endothelial dysfunction that underlies early atherosclerotic lesion formation.

No MeSH data available.


Related in: MedlinePlus