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

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-alpha, interleukin-1beta (IL-1beta), and cyclooxygenase (COX)-2, at a concentration of 20 microM. Flavonoids also prevented oxidative stress in activated monocytes, as demonstrated by their inhibitory effects on intracellular reactive oxygen species (ROS) and N(epsilon)-(carboxymethyl)lysine formation caused by HG. These inhibitory effects may involve inhibition of nuclear factor-kappaB 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.

• Authors: Chi-Hao Wu, Cheng-Feng Wu, Hsiao-Wen Huang, Ya-Chien Jao, Gow-Chin Yen
• Journal: Molecular nutrition & food research (Mol Nutr Food Res) Vol. 53 Issue 8 Pg. 984-95 (Aug 2009) ISSN: 1613-4133 [Electronic] Germany
• PMID: 19557821 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Flavonoids
• RNA, Messenger
• Receptor for Advanced Glycation End Products
• Receptors, Immunologic
• Transcription Factor RelA
• N(6)-carboxymethyllysine
• Cyclooxygenase 2
• PTGS2 protein, human
• NADPH Oxidases
• neutrophil cytosolic factor 1
• Protein Kinase C
• Extracellular Signal-Regulated MAP Kinases
• p38 Mitogen-Activated Protein Kinases
• Lysine

Topics

• Cells, Cultured
• Cyclooxygenase 2 (genetics)
• Cytokines (genetics)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Flavonoids (pharmacology)
• Humans
• Hyperglycemia (immunology)
• Lysine (analogs & derivatives, biosynthesis)
• Monocytes (drug effects, immunology)
• NADPH Oxidases (biosynthesis)
• Oxidative Stress (drug effects)
• Phosphorylation
• Protein Kinase C (biosynthesis)
• RNA, Messenger (analysis)
• Receptor for Advanced Glycation End Products
• Receptors, Immunologic (metabolism)
• Transcription Factor RelA (metabolism)
• p38 Mitogen-Activated Protein Kinases (metabolism)