title: 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: Department of Food Science and Biotechnology, National Chung-Hsing University, Taichung 40227, Taiwan.
authors: Chi-Hao
authors: CH
authors: Wu
authors: Cheng-Feng
authors: CF
authors: Wu
authors: Hsiao-Wen
authors: HW
authors: Huang
authors: Ya-Chien
authors: YC
authors: Jao
authors: Gow-Chin
authors: GC
authors: Yen
mesh_terms: D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics; D016207:Cytokines / Q000235:genetics*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D006943:Hyperglycemia / Q000276:immunology*; D008239:Lysine / Q000031:analogs & derivatives / Q000096:biosynthesis; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D019255:NADPH Oxidases / Q000096:biosynthesis; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D011493:Protein Kinase C / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016207:Cytokines; D005419:Flavonoids; D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D051996:Transcription Factor RelA; C048496:N(6)-carboxymethyllysine; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D008239:Lysine