Lycopene inhibits NF-κB activation and adhesion molecule expression through Nrf2-mediated heme oxygenase-1 in endothelial cells

Abstract

The endothelial expression of cell adhesion molecules plays a leading role in atherosclerosis. Lycopene, a carotenoid with 11 conjugated double bonds, has been shown to have anti-inflammatory properties. In the present study, we demonstrate a putative mechanism for the anti-inflammatory effects of lycopene. We demonstrate that lycopene inhibits the adhesion of tumor necrosis factor α (TNFα)-stimulated monocytes to endothelial cells and suppresses the expression of intercellular cell adhesion molecule-1 (ICAM-1) at the transcriptional level. Moreover, lycopene was found to exert its inhibitory effects by blocking the degradation of the inhibitory protein, IκBα, following 6 h of pre-treatment. In TNFα-stimulated endothelial cells, nuclear factor-κB (NF-κB) nuclear translocation and transcriptional activity were abolished by up to 12 h of lycopene pre-treatment. We also found that lycopene increased the intracellular glutathione (GSH) level and glutamate-cysteine ligase expression. Subsequently, lycopene induced nuclear factor-erythroid 2 related factor 2 (Nrf2) activation, leading to the increased expression of downstream of heme oxygenase-1 (HO-1). The use of siRNA targeting HO-1 blocked the inhibitory effects of lycopene on IκB degradation and ICAM-1 expression. The inhibitory effects of lycopene thus appear to be mediated through its induction of Nrf2-mediated HO-1 expression. Therefore, the findings of the present study indicate that lycopene suppresses the activation of TNFα-induced signaling pathways through the upregulation of Nrf2-mediated HO-1 expression.

Anti-Inflammatory Effect of Lycopene on Experimental Spinal Cord Ischemia Injury via Cyclooxygenase-2 Suppression

“…Similarly, Choi et al [34] reported that santamarin decreased LPS-elicited inflammation via the activation of HO-1. It has also been previously described that lycopene upregulated HO-1 to repress inflammation [22, 35], which was in agreement with what we observed in our experiments: lycopene attenuated the SCII-induced reduction of HO-1. Furthermore, AMPK reportedly regulates the expression of HO-1 and/or COX-2 [36].…”

Lycopene ameliorates oxidative stress in the aging chicken ovary via activation of Nrf2/HO-1 pathway

“…The protective effect of lycopene against oxidative stress is via the activation of the Nrf2/HO-1 pathway [ 41 – 43 ]. Yang et al reported that lycopene suppressed the activation of the TNFα-induced signaling pathway through upregulation of the Nrf2-mediated HO-1 expression in endothelial cells [ 51 ]. The Nrf2/HO-1 pathway represents the prime target for chemoprevention of cisplatin-induced nephrotoxicity by lycopene [ 52 ].…”

Lycopene Inhibit IMQ-Induced Psoriasis-Like Inflammation by Inhibiting ICAM-1 Production in Mice

“…Another study showed that increasing lycopene levels in the blood can reduce oxidative stress and improve endothelial cell function [10]. In addition, lycopene also inhibits NF-κB activation and adhesion molecule expression in endothelial cells [11]. In stomatology, lycopene plays a multifunctional role as a nonsurgical support in the treatment of oral diseases, including leukoplakia and oral submucous fibrosis [12].…”