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.

Differential hepatoprotective mechanisms of rutin and quercetin in CCl4-intoxicated BALB/cN mice

“…NF-κB is also involved in the regulation of COX-2 and iNOS gene expression by binding to their promoter regions [28] . COX-2 and iNOS exert a prominent role under inflammatory conditions by producing prostaglandins and NO · , respectively [29,30] . Thus, the antiinflammatory effect of quercetin and rutin in CCl 4 -injured liver could be attributed to the inhibition of the NF-κB pathway, which is in agreement with previous findings [31] .…”

Plant-Derived Agents with Anti-Glycation Activity

“…In addition, EGCG inhibited the phosphorylating activity of IKKβ kinase in an in vitro assay and also the AGE-mediated activation and DNA binding activity of NF-κB by suppressing the degradation of its inhibitory protein IκBα in the cytoplasm [142]. EGCG has also been shown to prevent intracellular AGEs formation and the production of proinflammatory cytokines in monocytes under hyperglycemic conditions [143]. EGCG is capable of trapping reactive dicarbonyl species, such as methylglyoxal and glyoxal, as demonstrated by Ho and coworkers in 2007 [144].…”

The Mechanisms of Inhibition of Advanced Glycation End Products Formation through Polyphenols in Hyperglycemic Condition

“…3) [19]. It should be noted that AGEs stimulate the differentiation of monocytes to macrophages (a kind of vascular cell) as well [20]. In an experiment AGEs altered the cholesterol transport system by decreasing special proteins for cholesterol efflux known as ABCA-1 and ABCG-1, which resulted in impaired cholesterol emission through bile and feces and caused cholesterol accumulation in the body [21].…”

“…However flavones (luteolin) showed the utmost inhibitory activity on ex-pression of inflammatory genes such as TNF-α, interleukin-1b, and cyclooxygenase-2 in hyperglycemia condition. The plausible explanation for their antiglycation abilities is a downregulation of RAGE-mRNA expression, which is an integral part of RAGE formation [20]. PPAR gamma, a member of the nuclear receptor proteins, has a pivotal role in carbohydrates and lipids metabolisms, via downregulation of RAGE expression or upregulation of paraoxonase-1 expression, a HDL-associated lipolactonase with antioxidative properties [104].…”