A Citrus Extract Containing Flavanones Represses Plasminogen Activator Inhibitor-1 (PAI-1) Expression and Regulates Multiple Inflammatory, Tissue Repair, and Fibrosis Genes in Human Colon Fibroblasts

Abstract

The consumption of flavonoid-rich Citrus extracts has been associated with multiple beneficial effects including anti-inflammatory properties, but the potential effects on the inflammatory responses in the gut have not been thoroughly investigated. We used microarrays to search for molecular changes induced in human colon fibroblasts in response to the exposure to a flavanone-rich bitter orange extract under physiologically representative conditions. Dietary nontoxic levels of the predigested extract induced moderate but significant changes in the expression of genes associated with tissue repair and inflammation. Among the top regulated genes, plasminogen activator inhibitor 1 (PAI-1) was downregulated, and the matrix metallopeptidase 12 (MMP-12) was upregulated (mRNA and protein levels). Both proteins are involved in extracellular matrix (ECM) remodeling and fibroblast migration. The extract also affected the fibroblast migration and reduced monocyte adhesion, but the response was different in unstimulated cells and in cells pretreated with TNF-alpha. Collectively, these results were indicative of a moderate activation of the colon fibroblast inflammation-related function after exposure to the extract. Further investigations are required to identify the in vivo role of this Citrus derived extract in the maintenance of the normal balance in the intestine and in the pathogenesis of inflammatory diseases.

Inhibition of Quorum Sensing (QS) in Yersinia enterocolitica by an Orange Extract Rich in Glycosylated Flavanones

“…The extract was composed of approximately 42.1% soluble flavanones (% of the powder extract) with one most abundant compound, naringin (24.5 ± 2.6%), followed by neohesperidin (11.4 ± 0.8%), hesperidin (1.7 ± 0.4%), naringenin (0.4 ± 0.1%), hesperetin (0.4 ± 0.1%), and isosakuranetin (0.2 ± 0.1%). 5 The structures of the three main flavanone constituents of the orange extract are shown in Figure 1. The extract (a hygroscopic brown powder, 2.1% humidity) was kept in a tightly closed container within a desiccator at room temperature, and fresh stock solutions were prepared by dissolving 0.1 g of the powder extract in 50 mL of water.…”

“…3 Therefore, these flavanone glycosides can reach the colon in their intact molecular form and may exert some effects on the microorganisms present in the distal part of the intestine. 4,5 Recently, several studies have demonstrated that certain flavonoids can act as inhibitors of the virulence of pathogenic bacteria by interfering with quorum sensing (QS) mechanisms. 6,7 QS is a regulatory mechanism that enables bacteria to make collective decisions with respect to the expression of a specific set of genes.…”

Effects of Fermented Rice Vinegar Kurozu and Its Sediment on Inflammation-Induced Plasminogen Activator Inhibitor 1 (PAI-1) Increase

“…This indicated that orally administered CK or KM can decrease thrombotic tendencies induced by inflammation in mice. We found that PAI-1 production was significantly suppressed in the plasma of mice after consuming CK and KM for four weeks, a time-frame that is appropriate to explore anti-thrombotic effects in mice [11] [25] [26].…”

“…Lin et al reported that green tea polyphenols inhibit PAI-1 expression and secretion in endothelial cells [10]. A citrus extract containing flavones represses PAI-1 expression in human colon fibroblasts [11].…”

In vitro evaluation of the cytotoxicity and modulation of mechanisms associated with inflammation induced by perfluorooctanesulfonate and perfluorooctanoic acid in human colon myofibroblasts CCD-18Co

“…For comparative purposes, the effect of both PFASs in presence or absence of IL-1b, an essential pro-inflammatory cytokine in mediating the inflammatory response (Powell et al, 2011) was investigated. Furthermore, since fetal bovine serum (FBS) can influence mechanisms associated to inflammation in these cells (Giménez-Bastida et al, 2009;González-Sarrías et al, 2010), and proteins of FBS such as albumin can interact with PFOS and PFOA (Chen and Guo, 2009) different concentrations of serum were used in this study. Therefore, the aim of this study was to perform an evaluation of the ability of PFOS and PFOA to induce cytotoxicity and modulate mechanisms associated with inflammation, including (i) colon fibroblasts viability, (ii) colon fibroblasts proliferation, and (iii) IL-6 production.…”