Chemical structure of flavonols in relation to modulation of angiogenesis and immune-endothelial cell adhesion

• Published in: The Journal of nutritional biochemistry 2006-03, Vol.17 (3), p.165-176
• Main Authors: Kim, Jong-Deog, Liu, Liping, Guo, Weimin, Meydani, Mohsen
• Format: Article
• Language: English
• Subjects: Angiogenesis; angiogenesis growth factor; anticarcinogenic activity; Antioxidant; antioxidant activity; antioxidants; Antioxidants - pharmacology; Biological and medical sciences; Blood vessels and receptors; cardioprotective effect; Cell adhesion; Cell Adhesion - drug effects; Cell Adhesion Molecules - genetics; cell culture; Cell Death - drug effects; Cell Division - drug effects; Cell Line; Cells, Cultured; chemical composition; Cytotoxicity; endothelial cells; Endothelial Cells - physiology; flavanoids; Flavonoids - pharmacology; Flavonols; Flavonols - chemistry; Flavonols - pharmacology; Flavonols - toxicity; free radicals; fruits (food); Fundamental and applied biological sciences. Psychology; galangin; Gene Expression - drug effects; health benefits; health promotion; Humans; Hydroxyl moiety; immune-endothelial cell adhesion; immunostimulants; kaempferol; Kaempferols - pharmacology; Monocytes - physiology; myricetin; Neovascularization, Physiologic - drug effects; quantitative structure-activity relationships; quercetin; Quercetin - pharmacology; Structure-Activity Relationship; Tetradecanoylphorbol Acetate - pharmacology; Umbilical Veins; Vascular Endothelial Growth Factor A - pharmacology; vascular endothelial growth factors; vegetables; Vertebrates: cardiovascular system
• ISSN: 0955-2863; 1873-4847
• DOI: 10.1016/j.jnutbio.2005.06.006

The antioxidant activity of flavonoids has been suggested to contribute to several health benefits associated with the consumption of fruits and vegetables. Four flavonols — myricetin (M), quercetin (Q), kaempferol (K) and galangin (G), all with different numbers of hydroxyl moieties (–OH) — were examined for their antioxidant activity and cytotoxicity on human umbilical vein endothelial cells (HUVECs) and for their potential antiangiogenic and cell adhesion effects. The relative antioxidant capacity of these flavonols in cell culture medium (cell-free system) and their intracellular antioxidant activity were M=Q>K=G, which correlated respectively with the presence of 3, 2, 1 and 0 moieties of –OH on their B-ring. The higher the numbers of –OH moieties on the B-ring the less toxic the flavonol was to HUVEC, and the LD50 was determined as: M (100 μM)>Q (50 μM)>K (20 μM)>G (10 μM). These flavonols at ≈0.5 LD50 doses suppressed the vascular endothelial growth factor (VEGF)-stimulated HUVEC tubular structure formation by: M (47%)>Q (37%)>K (15%)>G (14%), which was not linearly associated with their numbers of –OH moieties. However, the magnitude of flavonols' suppression of activated U937 monocytic cells adhesion to HUVEC was associated with the number of –OH moieties on the B-ring. This was prominent when U937 cells were pretreated with these flavonols. In contrast, the numbers of –OH moiety had no apparent influence on the adhesion or expression of adhesion molecules when activated HUVECs were pretreated with these flavonols. The presence of different numbers of –OH moieties on the B-ring of the flavonols may contribute to their antioxidant activity as well as their toxicity and may play an important role in their potency for biological action such as angiogenesis and immune-endothelial cell adhesion, which, respectively, are important processes in the development of cancer and atherosclerosis.