The Nutraceutical Dehydrozingerone and Its Dimer Counteract Inflammation‐ and Oxidative Stress‐Induced Dysfunction of In Vitro Cultured Human Endothelial Cells: A Novel Perspective for the Prevention and Therapy of Atherosclerosis

Abstract

Atherosclerosis is characterized by endothelial dysfunction, mainly induced by inflammation and oxidative stress. Increased reactive oxygen species (ROS) production together with increased adhesion molecules and thrombogenic tissue factor (TF) expression on endothelial cells has a key role in proatherogenic mechanisms. Therefore downmodulation of these molecules could be useful for reducing the severity of inflammation and atherosclerosis progression. Dehydrozingerone (DHZ) is a nutraceutical compound with anti-inflammatory and antioxidant activities. In this study we evaluated the ability of DHZ and its symmetric dimer to modulate hydrogen peroxide- (H2O2-) induced ROS production in human umbilical vein endothelial cells (HUVEC). We also evaluated intercellular adhesion molecule- (ICAM-) 1, vascular cell adhesion molecule- (VCAM-) 1, and TF expression in HUVEC activated by tumor necrosis factor- (TNF-) α. HUVEC pretreatment with DHZ and DHZ dimer reduced H2O2-induced ROS production and inhibited adhesion molecule expression and secretion. Of note, only DHZ dimer was able to reduce TF expression. DHZ effects were in part mediated by the inhibition of the nuclear factor- (NF-) κB activation. Overall, our findings demonstrate that the DHZ dimer exerts a potent anti-inflammatory, antioxidant, and antithrombotic activity on endothelial cells and suggest potential usefulness of this compound to contrast the pathogenic mechanisms involved in atherosclerosis progression.

Anti-inflammatory property of Parkia speciosa empty pod extract in human umbilical vein endothelial cells

“…increased NF-κB p65 protein expression in HUVECs as similarly reported in other studies (Cao et al, 2009;Profumo et al, 2016). NF-B protein complex is involved in several cellular responses to stimuli, such as free radicals, stress, and cytokines (Donato et al, 2015), associated with activation of adhesion molecules, chemokines, and cytokines (Valen et al, 2001).…”

Synthesis, Anti-inflammatory, and Antioxidant Activity of Mannich Bases of Dehydrozingerone Derivatives

“…Like as curcumin, the compound also exhibits a wide range of biological activities such as anti-inflammatory, antioxidant, antimicrobial, and cytotoxic activity. [1][2][3][4][5][6][7][8] Various chemical modification of DHZ has been performed to exploit for diverse biological activities of DHZ derivatives, such as esterification or alkylation of OH phenolic group, replacement of OH with other substituents, substitution of the methoxy group, reduction of double bond, cyclization of α,β-unsaturated carbonyl, and substitution of hydrogen atom bound to the carbonyl α-carbon. 2,4,[9][10][11] Some Mannich bases of DHZ have been synthesized and reported to have better anti-inflammatory activity compared to DHZ and fairly good anti-inflammatory activity compared to indomethacin.…”

A review of molecular imaging of atherosclerosis and the potential application of dendrimer in imaging of plaque

“…27 The increased endothelial permeability allows lipids to penetrate across the arterial wall, especially oxidized low-density lipoprotein (oxLDL), which can impair endothelial cell (EC) and induce expression of growth factors by the damaged EC, including monocyte chemotactic protein-1 (MCP-1), platelet-derived growth factor (PDGF), transforming growth factor beta (TGF-β), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and P-selectin and E-selectin expressed on the activated endothelial surface. This in turn promotes recruitment of monocytes to the vessel wall where monocytes roll along the activated endothelium and continuously absorb oxLDL through surface receptors, finally forming foam cells.…”