Delta- and gamma-tocotrienol isomers are potent in inhibiting inflammation and endothelial activation in stimulated human endothelial cells

• Main Authors: Abd Manaf, Ali, Suhaila, Muid, Hapizah, Mohd Nawawi
• Format: Article
• Language: English; English
• Published: 2016
• Subjects: QH301 Biology
• Online Access: http://eprints.unisza.edu.my/7587/1/FH02-FBIM-16-06892.jpg; http://eprints.unisza.edu.my/7587/2/FH02-FBIM-16-06957.jpg; http://eprints.unisza.edu.my/7587/

Background: Tocotrienols (TCTs) are more potent antioxidants than a-tocopherol (TOC). However, the effectiveness and mechanism of the action of TCT isomers as anti-atherosclerotic agents in stimulated human endothelial cells under inflammatory conditions are not well established. Aims: 1) To compare the effects of different TCT isomers on inflammation, endothelial activation, and endothelial nitric oxide synthase (eNOS). 2) To identify the two most potent TCT isomers in stimulated human endothelial cells. 3) To investigate the effects of TCT isomers on NFkB activation, and protein and gene expression levels in stimulated human endothelial cells. Methods: Human umbilical vein endothelial cells were incubated with various concentrations of TCT isomers or a-TOC (0.310 mM), together with lipopolysaccharides for 16 h. Supernatant cells were collected and measured for protein and gene expression of cytokines (interleukin-6, or IL-6; tumor necrosis factor-alpha, or TNF-a), adhesion molecules (intercellular cell adhesion molecule-1, or ICAM-1; vascular cell adhesion molecule-1, or VCAM-1; and e-selectin), eNOS, and NFkB. Results: d-TCT is the most potent TCT isomer in the inhibition of IL-6, ICAM-1, VCAM-1, and NFkB, and it is the second potent in inhibiting e-selectin and eNOS. g-TCT isomer is the most potent isomer in inhibiting e-selectin and eNOS, and it is the second most potent in inhibiting is IL-6, VCAM-1, and NFkB. For ICAM-1 protein expression, the most potent is d-TCT followed by a-TCT. a- and b-TCT inhibit IL-6 at the highest concentration (10 mM) but enhance IL-6 at lower concentrations. g-TCT markedly increases eNOS expression by 811-fold at higher concentrations (510 mM) but exhibits neutral effects at lower concentrations. Conclusion: d- and g-TCT are the two most potent TCT isomers in terms of the inhibition of inflammation and endothelial activation whilst enhancing eNOS, possibly mediated via the NFkB pathway. Hence, there is a great potential for TCT isomers as anti-atherosclerotic agents.