title: The flavonoid phloretin suppresses stimulated expression of endothelial adhesion molecules and reduces activation of human platelets.
abstract: 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.
authors.affiliation: Medizinische Klinik und Poliklinik, Schwerpunkt Kardiologie, Angiologie, Pneumologie, Charité der Humboldt-Universität, Campus Mitte, Berlin, Germany. verena.stangl@charite.de
authors.forename: Verena
authors.initials: V
authors.lastname: Stangl
authors.forename: Mario
authors.initials: M
authors.lastname: Lorenz
authors.forename: Antje
authors.initials: A
authors.lastname: Ludwig
authors.forename: Nicole
authors.initials: N
authors.lastname: Grimbo
authors.forename: Carola
authors.initials: C
authors.lastname: Guether
authors.forename: Wasiem
authors.initials: W
authors.lastname: Sanad
authors.forename: Sabine
authors.initials: S
authors.lastname: Ziemer
authors.forename: Peter
authors.initials: P
authors.lastname: Martus
authors.forename: Gert
authors.initials: G
authors.lastname: Baumann
authors.forename: Karl
authors.initials: K
authors.lastname: Stangl
mesh_terms: D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000235:genetics*; D019040:E-Selectin / Q000235:genetics; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D007375:Interleukin-1 / Q000494:pharmacology; D007700:Kinetics; D010693:Phloretin / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1 / Q000187:drug effects
chemical_list: D015815:Cell Adhesion Molecules; D019040:E-Selectin; D005419:Flavonoids; D007375:Interleukin-1; D014157:Transcription Factors; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D010693:Phloretin