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Naturally occurring flavonoids attenuate high glucose‐induced expression of proinflammatory cytokines in human monocytic THP‐1 cells
Author(s) -
Wu ChiHao,
Wu ChengFeng,
Huang HsiaoWen,
Jao YaChien,
Yen GowChin
Publication year - 2009
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.200800495
Subject(s) - proinflammatory cytokine , p38 mitogen activated protein kinases , chemistry , inflammation , nadph oxidase , reactive oxygen species , oxidative stress , glycation , biochemistry , protein kinase a , protein kinase c , kinase , luteolin , pharmacology , biology , quercetin , antioxidant , receptor , immunology
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 N ε ‐(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.