Objectives: In our previous research the antihypertensive properties of lycopene-containing tomato oleoresin have been revealed. The present study was aimed to assess if oleoresin interferes in the inflammatory signalling in endothelial cells, imitating reduction of inflammatory processes in the vessel wall and in this way to propose the mechanism for the reduction of blood pressure by oleoresin.
Methods and results: A wide number of functional and inflammatory markers were investigated in two cultured endothelial cell models [EA.hy926 and human umbilical vein endothelial cell (HUVEC)], exposed to oleoresin and carotenoids lycopene and lutein. All the carotenoids significantly improved basic endothelial function as measured by increased nitric oxide and decreased endothelin (ET-1) release. They were effective in attenuation of inflammatory nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signalling: decrease of tumour necrosis factor-alpha (TNF-α)-induced leukocytes adhesion, expression of adhesion molecules inter-cellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), and nuclear translocation of NF-κB components as well as some revert of inhibitor of kappa B (IκB) ubiquitination. In addition, the carotenoids were able to inhibit NF-κB activation in transfected endothelial cells. When combined with lutein, oleoresin exerted synergistic effect on preclusion of leukocytes adhesion.
Conclusions: Prevention of over-expression of adhesion molecules through inhibition of NF-κB signalling may be one of the main mechanisms driving carotenoids to attenuate inflammatory leukocyte adhesion to endothelium. This is the first profound study on the mechanisms involved in the positive action of natural tomato products in endothelial cells.
Soroka University Hospital, Faculty of Health Sciences, Ben-Gurion University, Beer Sheva, Israel
*Defined for equal contribution to the manuscript creation.
Correspondence to Esther Paran, Hypertension Unit, Soroka University Hospital, Beer Sheva 84101, Israel. Tel: +972 8647 9866; fax: +972 640 3102; e-mail: email@example.com
Abbreviations: eNOS, endothelial nitric oxide synthase; ET-1, endothelin; HUVEC, human umbilical vein endothelial cells; ICAM-1, inter-cellular adhesion molecule 1; IκB, inhibitor of kappa B; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; TNF-α, tumour necrosis factor-alpha; VCAM-1, vascular cell adhesion molecule 1
Received 14 March, 2012
Revised 14 August, 2012
Accepted 31 October, 2012