Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Stangl, V. et al.

Stangl, Lorenz, Ludwig, Grimbo, Guether, Sanad, Ziemer, Martus, Baumann, Stangl,

The flavonoid phloretin suppresses stimulated expression of endothelial adhesion molecules and reduces activation of human platelets.

Atherosclerosis is a chronic inflammatory disease accompanied by the expression of endothelial adhesion molecules. Phloretin is a plant-derived phytochemical that is mainly present in apples. Because phloretin is reported to promote antioxidative activities, we investigated the effects of phloretin on cytokine-induced expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule-1 (E-selectin) in human umbilical vein endothelial cells (HUVECs). Phloretin prevented TNF-alpha- stimulated upregulation of VCAM-1, ICAM-1, and E-selectin expression in a concentration-dependent manner. To the same extent as for TNF-alpha, phloretin also inhibited IL-1beta-induced upregulation in expression of all 3 adhesion molecules. Inhibition of cytokine-induced adhesion molecule expression for VCAM-1, ICAM-1, and E-selectin was detected already at the level of mRNA. Preincubation with phloretin dose-dependently attenuated TNF-alpha-stimulated adhesion of monocytic THP-1 cells to HUVECs and human aortic endothelial cells. Phloretin did not affect TNF-alpha- stimulated activation of nuclear factor kappaB (NF-kappaB) but inhibited activation of interferon regulatory factor 1, a transcription factor involved in the regulation of endothelial cell adhesion molecule expression. In human platelets, phloretin diminished adenosine diphosphate (ADP) and thrombin receptor- activating peptide- stimulated expression of the activated form of the GPIIb/IIIa complex and reduced platelet aggregation stimulated by ADP. Thus phloretin may have beneficial effects in the onset and progression of cardiovascular diseases.[1]

References

The flavonoid phloretin suppresses stimulated expression of endothelial adhesion molecules and reduces activation of human platelets. Stangl, V., Lorenz, M., Ludwig, A., Grimbo, N., Guether, C., Sanad, W., Ziemer, S., Martus, P., Baumann, G., Stangl, K. J. Nutr. (2005) [Pubmed]

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