Metabolic conversion of dietary flavonoids alters their anti-inflammatory and antioxidant properties |
| |
Authors: | Lotito Silvina B Zhang Wei-Jian Yang Chung S Crozier Alan Frei Balz |
| |
Institution: | a Linus Pauling Institute, Oregon State University, Corvallis, OR, USAb The State University of New Jersey, NJ, USAc School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK |
| |
Abstract: | The notion that dietary flavonoids exert beneficial health effects in humans is often based on in vitro studies using the glycoside or aglycone forms of these flavonoids. However, flavonoids are extensively metabolized in humans, resulting in the formation of glucuronide, methyl, and sulfate derivatives, which may have different properties than their parent compounds. The goal of this study was to investigate whether different chemical modifications of the same flavonoid molecule affect its biological and antioxidant activities. Hence, we studied the anti-inflammatory effects of several major human metabolites of quercetin and (-)-epigallocatechin-3-O-gallate (EGCG) by assessing their inhibitory effects on tumor necrosis factor α (TNFα)-induced protein expression of cellular adhesion molecules in human aortic endothelial cells (HAEC). HAEC were incubated with 1-30 μM quercetin, 3'- or 4'-O-methyl-quercetin, quercetin-3-O-glucuronide, and quercetin-3'-O-sulfate or 20-100 μM EGCG, 4'-O-methyl-EGCG, and 4',4'-di-O-methyl-EGCG, prior to coincubation with 100 U/ml of TNFα. 3'-O-Methyl-quercetin, 4'-O-methyl-quercetin, and their parent aglycone compound, quercetin, all effectively inhibited expression of intercellular adhesion molecule-1 (ICAM-1) with IC(50) values (concentration required for 50% inhibition) of 8.0, 5.0, and 4.4 μM, respectively; E-selectin expression was suppressed to a somewhat lesser but still significant degree by all three compounds, whereas vascular cell adhesion molecule-1 (VCAM-1) was not affected. In contrast, quercetin-3-O-glucuronide (20-100 μM), quercetin-3'-O-sulfate (10-30 μM), and phenolic acid metabolites of quercetin (20-100 μM) did not inhibit adhesion molecule expression. 4',4'-Di-O-methyl-EGCG selectively inhibited ICAM-1 expression with an IC(50) value of 94 μM, whereas EGCG (20-60 μM) and 4'-O-methyl-EGCG (20-100 μM) had no effect. The inhibitory effects of 3'-O-methyl-quercetin and 4',4'-di-O-methyl-EGCG on adhesion molecule expression were not related either to inhibition of NF-κB activation or to their antioxidant reducing capacity. Our data indicate that flavonoid metabolites have different biological and antioxidant properties than their parent compounds, and suggest that data from in vitro studies using nonmetabolites of flavonoids are of limited relevance in vivo. |
| |
Keywords: | COMT catechol-O-methyl transferase EGCG (&minus )-epigallocatechin-3-O-gallate ELISA enzyme-linked immunosorbent assay FBS fetal bovine serum FRAP ferric reducing antioxidant parameter HAEC human aortic endothelial cells HUVEC human umbilical vein endothelial cells ICAM-1 intercellular adhesion molecule-1 IC50 concentration required for 50% inhibition NF-κB nuclear factor-kappa B MCP-1 monocyte chemotactic protein-1 TNFα tumor necrosis factor α VCAM-1 vascular cell adhesion molecule-1 |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|