Delta- and gamma-tocotrienol isomers are potent in inhibiting inflammation and endothelial
activation in stimulated human endothelial cells
Sammanfattning
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 NF?B 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 (0.3–10 µM), 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 NF?B.
Results: d-TCT is the most potent TCT isomer in the inhibition of IL-6, ICAM-1, VCAM-1, and NF?B, and
it is the second potent in inhibiting e-selectin and eNOS. ?-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
NF?B. For ICAM-1 protein expression, the most potent is d-TCT followed by a-TCT. a- and ß-TCT inhibit
IL-6 at the highest concentration (10 µM) but enhance IL-6 at lower concentrations. ?-TCT markedly
increases eNOS expression by 8-11-fold at higher concentrations (5-10 µM) but exhibits neutral
effects at lower concentrations.
Conclusion: d- and ?-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 NF?B
pathway. Hence, there is a great potential for TCT isomers as anti-atherosclerotic agents.