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.

Highlights

  • Chronic subacute inflammation and oxidative stress leading to endothelial dysfunction underlie the early pathogenesis of atherosclerosis [1, 2]

  • We have investigated whether HIPER, Evidence-Based Complementary and Alternative Medicine a combination of these ingredients, could protect human coronary artery endothelial cells (HCAECs) from cytokineinduced inflammatory and oxidative stress responses

  • TNF-α treatment increased NADPH oxidase 4 (NOX4) expression by 15%, a result that was abrogated in HCAECs pretreated with 25 or 50 μL/mL

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Summary

Introduction

Chronic subacute inflammation and oxidative stress leading to endothelial dysfunction underlie the early pathogenesis of atherosclerosis [1, 2]. The interaction of monocytes with endothelial cells is mediated by cell adhesion molecules, the most important of which are vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1) expressed by the endothelial cells [4]. The expression of both VCAM-1 and ICAM-1 is regulated by nuclear factor-kappa B (NF-κB), a transcription factor that is activated by oxidative stress. Inflammation and oxidative stress are considered key targets to improving or reversing endothelial dysfunction associated with early atherosclerotic plaque formation [1, 2]. This antiinflammatory effect is most likely due to the effect of HIPER on lowering intracellular ROS levels

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