Metabolic conversion of dietary flavonoids alters their anti-inflammatory and antioxidant properties

Lotito, S.B., Zhang, W.-J., Yang, C.S., Crozier, A. and Frei, B. (2011) Metabolic conversion of dietary flavonoids alters their anti-inflammatory and antioxidant properties. Free Radical Biology and Medicine, 51(2), pp. 454-463. (doi: 10.1016/j.freeradbiomed.2011.04.032)

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 a (TNF alpha)-induced protein expression of cellular adhesion molecules in human aortic endothelial cells (HAEC). HAEC were incubated with 1-30 mu M quercetin, 3'- or 4'-O-methyl-quercetin, quercetin-3-O-glucuronide, and quercetin-3'-O-sulfate or 20-100 mu M EGCG, 4 ''-O-methyl-EGCG, and 4',4 ''-di-O-methyl-EGCG, prior to coincubation with 100 U/ml of TNF alpha. 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 IC50 values (concentration required for 50% inhibition) of 8.0, 5.0, and 4.4 mu M, 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 mu M), quercetin-3'-O-sulfate (10-30 mu M), and phenolic acid metabolites of quercetin (20-100 mu M) did not inhibit adhesion molecule expression. 4',4 ''-Di-O-methyl-EGCG selectively inhibited ICAM-1 expression with an IC50 value of 94 mu M, whereas EGCG (20-60 mu M) and 4 ''-O-methyl-EGCG (20-100 mu M) 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-kappa B 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. (C) 2011 Elsevier Inc. All rights reserved

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Crozier, Professor Alan
• Authors: Lotito, S.B., Zhang, W.-J., Yang, C.S., Crozier, A., and Frei, B.
• College/School: College of Medical Veterinary and Life Sciences
• Journal Name: Free Radical Biology and Medicine
• ISSN: 0891-5849