Luteolin inhibits the nuclear factor-kappa B transcriptional activity in Rat-1 fibroblasts.
ABSTRACT Flavonoids are natural polyphenolic compounds that have anti-inflammatory, cytoprotective and anticarcinogenic effects. In this study, we investigated the effects of several flavonoids on nuclear factor-kappa B (NF-kappa B) activation by using luciferase reporter gene assay. Among the flavonoids examined, luteolin showed the most potent inhibition on lipopolysaccharide (LPS)-stimulated NF-kappa B transcriptional activity in Rat-1 fibroblasts. Luteolin did not inhibit either I kappa B alpha degradation or NF-kappa B nuclear translocation, DNA binding or phosphorylation by LPS. However, luteolin prevented LPS-stimulated interaction between the p65 subunit of NF-kappa B and the transcriptional coactivator CBP. In addition, a specific PKA inhibitor that blocked the phosphorylation of CREB and c-Jun by luteolin partially reversed the inhibitory effect of luteolin on NF-kappa B.CBP complex formation and NF-kappa B transcriptional activity by LPS. These data imply that inhibition of NF-kappa B transcriptional activity by luteolin may occur through competition with transcription factors for coactivator that is available in limited amounts. Taken together, this study provides a molecular basis for the understanding of the anti-inflammatory effects of luteolin.
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ABSTRACT: The flavonoid luteolin has various pharmacological activities. However, only few studies exist on the in vivo mechanism underlying the actions of luteolin in hepatic steatosis and obesity. The aim of the current study was to elucidate the action of luteolin on obesity and its comorbidity by analyzing its transcriptional and metabolic responses, in particular the luteolin-mediated cross-talk between liver and adipose tissue in diet-induced obese mice. C57BL/6J mice were fed a normal, high-fat, and high-fat + 0.005% (w/w) luteolin diet for 16 weeks. In high-fat-fed mice, luteolin improved hepatic steatosis by suppressing hepatic lipogenesis and lipid absorption. In adipose tissue, luteolin increased PPARγ protein expression to attenuate hepatic lipotoxicity, which may be linked to the improvement circulating fatty acid levels by enhancing fatty acid uptake genes and lipogenic genes and proteins in adipose tissue. Interestingly, luteolin also up-regulated the expression of genes controlling lipolysis and the tricarboxylic acid (TCA) cycle prior to LD formation, thereby reducing adiposity. Moreover, luteolin improved hepatic insulin sensitivity by suppressing SREBP1 expression that modulates Irs2 expression through its negative feedback and gluconeogenesis. Luteolin ameliorates the deleterious effects of diet-induced obesity and its comorbidity via the interplay between liver and adipose tissue. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.Diabetes 12/2014; DOI:10.2337/db14-0631 · 7.90 Impact Factor
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ABSTRACT: Microglial activation is one of the causative factors for neuroinflammation, which is associated with the pathophysiology of neurodegenerative diseases. Our previous study showed that the flavonoid luteolin inhibited several pro-inflammatory enzymes and pro-inflammatory cytokines that are induced by activated microglia; however, its effect on signaling pathways is currently unknown. The present study examined the effects of luteolin on signaling pathways stimulated by lipopolysaccharide (LPS), including Toll-like receptor-4 (TLR-4), nuclear transcription factor-κB (NF-κB), mitogen-activated protein kinase (MAPK) family and protein kinase B (Akt) pathways in murine microglial BV2 cells. In addition, BV2 microglia and SH-SY5Y neuroblastoma cells were cocultured to observe the indirect neuroprotective effects of luteolin. Luteolin inhibited the LPS-stimulated expression of TLR-4. In addition, luteolin blocked LPS-induced NF-κB, p38, JNK and Akt activation, but had no effect on ERK. When SH-SY5Y cells were cocultured with LPS-stimulated BV2 microglia, pretreatment with luteolin increased neuronal viability and reduced the number of apoptotic cells. These data suggest that luteolin has a beneficial effect on neuroinflammatory events in neurodegenerative diseases via suppression of the NF-κB, MAPK and Akt pathways in activated microglial cells.Experimental and therapeutic medicine 05/2014; 7(5):1065-1070. DOI:10.3892/etm.2014.1564 · 0.94 Impact FactorThis article is viewable in ResearchGate's enriched formatRG Format enables you to read in context with side-by-side figures, citations, and feedback from experts in your field.
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ABSTRACT: Several hydrophilic and hydrophobic 1-alkyl-3-methylimidazole ionic liquids (ILs) were screened for their dissolution ability of luteolin to determine the IL suitable for extraction of luteolin from peanut shells. The experimental data indicated that hydrophilic 1-butyl-3-methyl-imidazolium nitrate ([C4mim]NO3) shows considerably higher dissolution ability of luteolin than commonly used organic solvents and other ILs investigated, which can be used as an efficient substitute of organic solvent for extraction of luteolin. The extraction of luteolin from peanut shells was performed using [C4mim]NO3 aqueous solution as solvent, and extraction conditions were analyzed and optimized by response surface methodology (RSM) with central composite design (CCD). Extraction temperature has significant effect on the yield of luteolin, followed by [C4mim]NO3 concentration. Under the optimal conditions namely liquid–solid ratio of 7.6 mL g−1, temperature of 100 °C and [C4mim]NO3 aqueous solution of 49%, determined by RSM, the yield of luteolin was 79.8 ± 1.48%, which was close to the 78.4% predicted by RSM.Separation and Purification Technology 10/2014; 135:223–228. DOI:10.1016/j.seppur.2014.08.022 · 3.07 Impact Factor