QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Stangl, V. Articles by Stangl, K. Search for Related Content PubMed PubMed Citation Articles by Stangl, V. Articles by Stangl, K.

---

Biochemical and Molecular Actions of Nutrients

The Flavonoid Phloretin Suppresses Stimulated Expression of Endothelial Adhesion Molecules and Reduces Activation of Human Platelets

Verena Stangl^*,1, Mario Lorenz^*, Antje Ludwig^*, Nicole Grimbo^*, Carola Guether^*, Wasiem Sanad^*, Sabine Ziemer, Peter Martus^**, Gert Baumann^* and Karl Stangl^*

^* Medizinische Klinik und Poliklinik, Schwerpunkt Kardiologie, Angiologie, Pneumologie; Institut für Laboratoriumsmedizin und Pathobiochemie; and ^** Institut für Medizinische Informatik, Biometrie und Epidemiologie, Charité der Humboldt-Universität, Campus Mitte, Berlin, Germany

¹To whom correspondence should be addressed. E-mail: verena.stangl{at}charite.de.

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--stimulated upregulation of VCAM-1, ICAM-1, and E-selectin expression in a concentration-dependent manner. To the same extent as for TNF-, phloretin also inhibited IL-1ß-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--stimulated adhesion of monocytic THP-1 cells to HUVECs and human aortic endothelial cells. Phloretin did not affect TNF--stimulated activation of nuclear factor B (NF-B) 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.

KEY WORDS: • phloretin • adhesion molecules • platelets • cytokines • atherosclerosis

This article has been cited by other articles:

				Y.-P. Lei, H.-W. Chen, L.-Y. Sheen, and C.-K. Lii Diallyl Disulfide and Diallyl Trisulfide Suppress Oxidized LDL-Induced Vascular Cell Adhesion Molecule and E-Selectin Expression through Protein Kinase A- and B-Dependent Signaling Pathways J. Nutr., June 1, 2008; 138(6): 996 - 1003. [Abstract] [Full Text] [PDF]

				M. Lorenz, B. Hewing, J. Hui, A. Zepp, G. Baumann, A. Bindereif, V. Stangl, and K. Stangl Alternative splicing in intron 13 of the human eNOS gene: a potential mechanism for regulating eNOS activity FASEB J, May 1, 2007; 21(7): 1556 - 1564. [Abstract] [Full Text] [PDF]