Gingerenone A Attenuates Monocyte‐Endothelial Adhesion via Suppression of I Kappa B Kinase Phosphorylation

Abstract

During the early stages of atherosclerosis, monocytes bind and migrate into the endothelial layer, promoting inflammation within the aorta. In order to prevent the development of atherosclerosis, it is critical to inhibit such inflammation. The therapeutic effects of ginger have been investigated in several models of cardiovascular disease. However, although a number of previous studies have focused on specific compounds, the mechanisms of action responsible remain unclear. Here, we investigated five major compounds present in ginger, and observed that gingerenone A exhibited the strongest inhibitory effects against tumor necrosis factor (TNF)-α and lipopolysaccharide (LPS) induced monocyte-endothelial adhesion. Furthermore, gingerenone A significantly suppressed the expression of TNF-α and LPS-induced vascular cell adhesion molecule-1 (VCAM-1) and chemokine (C-C motif) ligand 2 (CCL2), key mediators of the interaction between monocytes, and endothelial cells. Transactivation of nuclear factor-κB (NF-κB), which is a key transcription factor of VCAM-1 and CCL2, was induced by TNF-α and LPS, and inhibited by treatment of gingerenone A. Gingerenone A also inhibited the phosphorylation of NF-κB inhibitor (IκB) α and IκB Kinase. Taken together, these results demonstrate that gingerenone A attenuates TNF-α and LPS-induced monocyte adhesion and the expression of adhesion factors in endothelial cells via the suppression of NF-κB signaling. J. Cell. Biochem. 119: 260-268, 2018. © 2017 Wiley Periodicals, Inc.

Benefits of Ginger as Medicine for COVID-19: Literature Study

“…In addition to chemokines, cell adhesion molecules play a major role in leukocyte migration to infl amed organs. Zerumbone and gingerenone inhibit the expression of ICAM-1 and VCAM-1 [97,98].…”

Molecular mechanisms and genetic regulation in atherosclerosis

“…On the other hand, SIRT-3 and SIRT6 overexpression reduced atherogenesis in mice. The deletion of TNF-α/β [ 26 ] and MCP-1 genes [ 27 ] prevented vascular inflammation, adhesion molecules expression, collagen (I, III), ECM protein deposition and AS plaque formation by inhibiting aforesaid pathways in mice [ [28] , [29] , [30] , [31] ]. Interestingly, overexpression of P2Y2 nucleotide receptor (P2Y2R), which regulates vascular inflammation and AS plaque formation, correlate with increased production of vascular adhesion molecule and inflammation by activating TNF-β/Akt/NF-κB pathway in the AS susceptible region in the aorta.…”

6‐Dihydroparadol, a Ginger Constituent, Enhances Cholesterol Efflux from THP‐1‐Derived Macrophages

“…Several studies also suggested that consumption of ginger and its major bioactive constituents are associated with decreased risk of cardiovascular diseases (CVD), such as hypertension and atherosclerosis. [5,6] Ginger was reported to be used for the prevention of hypertension, which is supported by studies showing the inhibition of angiotensin-1-converting enzyme by ginger[7] as well as the inhibition of angiotensin II type 1 receptor (AT 1 ) activation by 6-gingerol. [8] Ginger and its major bioactive constituents also led to a significant reduction in platelet aggregation, which plays a central role in hemostasis and thrombosis.…”