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

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.

Indicaxanthin from Opuntia ficus-indica Fruit Ameliorates Glucose Dysmetabolism and Counteracts Insulin Resistance in High-Fat-Diet-Fed Mice

“…Their inhibition could be, therefore, crucial to explain the beneficial effects exerted by the pigment against the HFD-induced macrophage infiltration, activation and IR development. The ability of indicaxanthin to inhibit NF-κB signalling in this HFD model is consistent with our previous observations in other inflammatory-related models, where the yellow betalain was shown to counteract inflammation and tumour progression via NF-κB inhibition, both in vivo and in vitro [ 26 , 27 , 28 , 29 , 54 , 55 ].…”

“…In terms of biochemical mechanisms, disruption of glucose homeostasis can be envisaged as the result of a self-feeding cycle between systemic, chronic inflammation and oxidative stress, initiated by excess nutrient consumption. Along these lines, one potential explanation for the beneficial effects of indicaxanthin supplementation on insulin sensitivity may lie in its anti-inflammatory properties [ 25 , 26 , 28 , 54 , 55 ].…”

“…Along these lines, significant reducing, anti-oxidative, anti-inflammatory, anti-proliferative, anti-tumoral, spasmolytic and neuromodulatory and neuroprotective [ 24 ] effects of indicaxanthin have been reported both in vitro and in vivo [ 21 ]. Interestingly, NF-κB has been proposed as one of the crucial molecular targets that indicaxanthin can interact with, to exert its anti-inflammatory effects [ 25 , 26 , 27 , 28 , 29 ].…”

Downregulation of LncRNA NORAD promotes Ox-LDL-induced vascular endothelial cell injury and atherosclerosis

“…Monocytes migrate to the subendothelial space and become the activated macrophages, which uptake ox-LDL to become foam cells, and the atherosclerotic plaque is thus formed [38]. The expression of the endothelial adhesion molecules ICAM and VCAM is controlled by NF-κB [39]. Considering that the NF-κB pathway is activated by silencing NORAD, we further examined the changes of ICAM and VCAM levels.…”

Redox and autonomic responses to acute exercise-post recovery following Opuntia ficus-indica juice intake in physically active women

“…We observed that the plasma hydroperoxides significantly increased after testing, however the increase was smaller in the group supplemented with OFI than placebo group, thus suggesting that OFI juice was able to limit the formation of ROS and increase antioxidant capacity. Our previous study [ 16 ] and the known activity of indicaxanthin as an antioxidant and modulator of the redox balance of cells under a number of pathophysiological conditions [ 34 , 35 ] suggest a role for this phytochemical in the observed effect. With respect to OFI supplementation, Khouloud et al 18 following an intermittent yo-yo maximal aerobic effort test, not only described a decrease of oxidative stress following OFI supplementation, but also a reduction in the total and LDL cholesterol.…”