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Naturally occurring flavonoids attenuate high glucose‐induced expression of proinflammatory cytokines in human monocytic THP‐1 cells

Naturally occurring flavonoids attenuate high glucose‐induced expression of proinflammatory... Activation of circulating monocytes by hyperglycemia is bound to play a role in inflammatory and atherosclerosis. In this study, we examined whether flavonoids (catechin, EGCG, luteolin, quercetin, rutin) – phytochemicals that may possible belong to a new class of advanced glycation end products (AGEs) inhibitors – can attenuate high glucose (15 mmol/L, HG)‐induced inflammation in human monocytes. Our results show that all flavonoids significantly inhibited HG‐induced expression of proinflammatory genes and proteins, including TNF‐α, interleukin‐1β (IL‐1β), and cyclooxygenase (COX)‐2, at a concentration of 20 μM. Flavonoids also prevented oxidative stress in activated monocytes, as demonstrated by their inhibitory effects on intracellular reactive oxygen species (ROS) and Nε‐(carboxymethyl)lysine formation caused by HG. These inhibitory effects may involve inhibition of nuclear factor‐κB activation and may be supported by downregulation of the following: i) PKC‐dependent NADPH oxidase pathway; ii) phosphorylation of p38 mitogen‐activated protein kinase and extracellular signal‐regulated protein kinase, and iii) mRNA expression of receptor of AGEs. In addition, we found for the first time that lower levels of Bcl‐2 protein under HG conditions could be countered by the action of flavonoids. Our data suggest that, along with their antioxidant activities, flavonoids possess anti‐inflammatory properties and might therefore have additional protective effects against glycotoxin‐related inflammation. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Molecular Nutrition & Food Research Wiley

Naturally occurring flavonoids attenuate high glucose‐induced expression of proinflammatory cytokines in human monocytic THP‐1 cells

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References (39)

Publisher
Wiley
Copyright
Copyright © 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim
ISSN
1613-4125
eISSN
1613-4133
DOI
10.1002/mnfr.200800495
pmid
19557821
Publisher site
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Abstract

Activation of circulating monocytes by hyperglycemia is bound to play a role in inflammatory and atherosclerosis. In this study, we examined whether flavonoids (catechin, EGCG, luteolin, quercetin, rutin) – phytochemicals that may possible belong to a new class of advanced glycation end products (AGEs) inhibitors – can attenuate high glucose (15 mmol/L, HG)‐induced inflammation in human monocytes. Our results show that all flavonoids significantly inhibited HG‐induced expression of proinflammatory genes and proteins, including TNF‐α, interleukin‐1β (IL‐1β), and cyclooxygenase (COX)‐2, at a concentration of 20 μM. Flavonoids also prevented oxidative stress in activated monocytes, as demonstrated by their inhibitory effects on intracellular reactive oxygen species (ROS) and Nε‐(carboxymethyl)lysine formation caused by HG. These inhibitory effects may involve inhibition of nuclear factor‐κB activation and may be supported by downregulation of the following: i) PKC‐dependent NADPH oxidase pathway; ii) phosphorylation of p38 mitogen‐activated protein kinase and extracellular signal‐regulated protein kinase, and iii) mRNA expression of receptor of AGEs. In addition, we found for the first time that lower levels of Bcl‐2 protein under HG conditions could be countered by the action of flavonoids. Our data suggest that, along with their antioxidant activities, flavonoids possess anti‐inflammatory properties and might therefore have additional protective effects against glycotoxin‐related inflammation.

Journal

Molecular Nutrition & Food Research – Wiley

Published: Aug 1, 2009

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