Indicaxanthin from Opuntia ficus indica (L. Mill) Inhibits Oxidized LDL-Mediated Human Endothelial Cell Dysfunction through Inhibition of NF-κB Activation.

Alessandro Attanzio,Mario Allegra,Rosalia Busa’,Luisa Tesoriere,Anna Frazzitta,Maria A Livrea

doi:10.1155/2019/3457846

Alessandro Attanzio, Mario Allegra + Show 4 more

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https://doi.org/10.1155/2019/3457846

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Abstract

Oxidized low-density lipoproteins (oxLDL) play a pivotal role in the etiopathogenesis of atherosclerosis through the activation of inflammatory signaling events eventually leading to endothelial dysfunction and senescence. In the present work, we investigated the effects of indicaxanthin, a bioavailable, redox-modulating phytochemical from Opuntia ficus indica fruits, with anti-inflammatory activity, against oxLDL-induced endothelial dysfunction. Human umbilical vein cord cells (HUVEC) were stimulated with human oxLDL, and the effects of indicaxanthin were evaluated in a range between 5 and 20 μM, consistent with its plasma level after a fruit meal (7 μM). Pretreatment with indicaxanthin significantly and concentration-dependently inhibited oxLDL-induced cytotoxicity; ICAM-1, VCAM-1, and ELAM-1 increase; and ABC-A1 decrease of both protein and mRNA levels. From a mechanistic perspective, we also provided evidence that the protective effects of indicaxanthin were redox-dependent and related to the pigment efficacy to inhibit NF-κB transcriptional activity. In conclusion, here we demonstrate indicaxanthin as a novel, dietary phytochemical, able to exert significant protective vascular effects in vitro, at nutritionally relevant concentrations.

Highlights

Atherosclerosis is a long, multifactorial, inflammatory process characterized by the accumulation of lipids in the wall of large- and medium-sized arteries [1, 2]
We investigated the effects of indicaxanthin, a bioavailable, redox-modulating phytochemical from Opuntia ficus indica fruits, with anti-inflammatory activity, against Oxidized low-density lipoproteins (oxLDL)-induced endothelial dysfunction
The enhanced endothelial permeability favors the influx of LDL into the subendothelial intima where the inflammatory cells generate reactive oxygen and nitrogen species (RONS) inducing a progressive LDL oxidation. oxLDL, interact with endothelial cells (EC), disrupt the antioxidant defences of vascular endothelium, and boost leukocyte chemotaxis, reinforcing the whole inflammatory reaction that leads to a persistent EC dysfunction

Summary

Introduction

Atherosclerosis is a long, multifactorial, inflammatory process characterized by the accumulation of lipids in the wall of large- and medium-sized arteries [1, 2]. In areas at risk of atherosclerosis (e.g., at arterial bifurcations), the turbulent blood flow induces an endothelial activation, characterized by a local inflammatory response that generates an endocellular oxidative and nitrosative stress [3]. The increased levels of reactive oxygen and nitrogen species (RONS) activates selected redox-dependent transcription factors, such as NF-κB, that in turn induce an overexpression of endothelial adhesion molecules such as ICAM-1, VCAM-1, and ELAM-1 [1, 2]. This phenomenon increases the adhesion of leukocytes that eventually transmigrate in the subendothelial space where they are converted in macrophages. A chronic systemic inflammatory response is established and eventually results in the proliferation of macrophagic foam cells and the formation of fatty streaks, the hallmark of the early atherosclerotic lesions [3]

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