Dual mechanisms of NF-kappaB inhibition in carnosol-treated endothelial cells

Toxicology and Applied Pharmacology
Kai-Cheng LianYung-Wei Sun

Abstract

The increased adhesion of monocytes to injured endothelial layers is a critical early event in atherogenesis. Under inflammatory conditions, there is increased expression of specific cell adhesion molecules on activated vascular endothelial cells, which increases monocyte adhesion. In our current study, we demonstrate a putative mechanism for the anti-inflammatory effects of carnosol, a diterpene derived from the herb rosemary. Our results show that both carnosol and rosemary essential oils inhibit the adhesion of TNFalpha-induced monocytes to endothelial cells and suppress the expression of ICAM-1 at the transcriptional level. Moreover, carnosol was found to exert its inhibitory effects by blocking the degradation of the inhibitory protein IkappaBalpha in short term pretreatments but not in 12 h pretreatments. Our data show that carnosol reduces IKK-beta phosphorylation in pretreatments of less than 3 h. In TNFalpha-treated ECs, NF-kappaB nuclear translocation and transcriptional activity was abolished by up to 12 h of carnosol pretreatment and this was blocked by Nrf-2 siRNA. The long-term inhibitory effects of carnosol thus appear to be mediated through its induction of Nrf-2-related genes. The inhibition of ICAM-1 expressio...Continue Reading

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Citations

Nov 23, 2013·Free Radical Biology & Medicine·Takumi SatohStuart A Lipton
Mar 5, 2016·Evidence-based Complementary and Alternative Medicine : ECAM·Solomon Habtemariam
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Apr 16, 2011·Journal of Agricultural and Food Chemistry·Che-Yi ChaoHaw-Wen Chen

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