Dietary polyphenols have been associated with many beneficial cardiovascular effects. However, these effects are rather attributed to small phenolic metabolites formed by the gut microbiota, which reach sufficient concentrations in systemic circulation. 4-Methylcatechol (4-MC) is one such metabolite. As it is shown to possess considerable vasorelaxant effects, this study aimed to unravel its mechanism of action. To this end, experimental in vitro and in silico approaches were employed. In the first step, isometric tension recordings were performed on rat aortic rings. 4-MC potentiated the effect of cyclic nucleotides, but the effect was not mediated by either soluble guanylyl cyclase (sGC), modification of cyclic adenosine monophosphate levels, or protein kinase G. Hence, downstream targets such as calcium or potassium channels were considered. Inhibition of voltage-gated K+ channels (KV) markedly decreased the effect of 4-MC, and vasodilation was partly decreased by inhibition of the KV7 isoform. Contrarily, other types of K+ channels or L-type Ca2+ channels were not involved. In silico reverse docking confirmed that 4-MC binds to KV7.4 through hydrogen bonding and hydrophobic interactions. In particular, it interacts with two crucial residues for KV7.4 activation: Trp242 and Phe246. In summary, our findings suggested that 4-MC exerts vasorelaxation by opening KV channels with the involvement of KV7.4.
- MeSH
- aorta účinky léků metabolismus MeSH
- draslíkové kanály řízené napětím * metabolismus MeSH
- katecholy * farmakologie MeSH
- krysa rodu Rattus MeSH
- potkani Wistar MeSH
- quercetin * farmakologie MeSH
- simulace molekulového dockingu MeSH
- vazodilatace * účinky léků MeSH
- vazodilatancia farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- 4-methylcatechol MeSH Prohlížeč
- draslíkové kanály řízené napětím * MeSH
- katecholy * MeSH
- quercetin * MeSH
- vazodilatancia MeSH
Glucan particles (GPs) from Saccharomyces cerevisiae consist mainly of β-1,3-d-glucan. Curcumin is a phenolic compound of plant origin. A 24 h incubation with a mixture of GPs and curcumin increased the expression of the Nrf2 protein and increased the activation of the Nrf2-ARE system significantly.
- MeSH
- antioxidancia * chemie metabolismus farmakologie MeSH
- buňky Hep G2 MeSH
- faktor 2 související s NF-E2 metabolismus MeSH
- glukany chemie MeSH
- kurkumin * chemie farmakologie MeSH
- lidé MeSH
- oxidační stres účinky léků MeSH
- příprava léků MeSH
- Saccharomyces cerevisiae chemie MeSH
- THP-1 buňky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antioxidancia * MeSH
- faktor 2 související s NF-E2 MeSH
- glukany MeSH
- kurkumin * MeSH
- NFE2L2 protein, human MeSH Prohlížeč
The aim of the study was to broadly determine the biological activities of purple potato ethanolic extract of the Blue Congo variety (BCE). The antioxidant activity of BCE was determined in relation to liposome membranes, and peroxidation was induced by UVB and AAPH. To clarify the antioxidant activity of BCE, we investigated its interactions with hydrophilic and hydrophobic regions of a membrane using fluorimetric and FTIR methods. Next, we investigated the cytotoxicity and pro-apoptotic activities of BCE in two human colon cancer cell lines (HT-29 and Caco-2) and in normal cells (IPEC-J2). In addition, the ability to inhibit enzymes that are involved in pro-inflammatory reactions was examined. Furthermore, BCE interactions with serum albumin and plasmid DNA were investigated using steady state fluorescence spectroscopy and a single molecule fluorescence technique (TCSPC-FCS). We proved that BCE effectively protects lipid membranes against the process of peroxidation and successfully inhibits the cyclooxygenase and lipoxygenase enzymes. Furthermore, it interacts with the hydrophilic and hydrophobic parts of lipid membranes as well as with albumin and plasmid DNA. It was observed that BCE is more cytotoxic against colon cancer cell lines than normal IPEC-J2 cells; it also induces apoptosis in cancer cell lines, but does not induce cell death in normal cells.
- MeSH
- albuminy MeSH
- antioxidancia chemie farmakologie MeSH
- antitumorózní látky fytogenní chemie farmakologie MeSH
- inhibitory cyklooxygenasy chemie farmakologie MeSH
- inhibitory lipoxygenas chemie farmakologie MeSH
- lidé MeSH
- lipidy chemie MeSH
- liposomy MeSH
- nádorové buněčné linie MeSH
- plazmidy MeSH
- reaktivní formy kyslíku MeSH
- rostlinné extrakty chemie farmakologie MeSH
- sérový albumin chemie metabolismus MeSH
- Solanum tuberosum chemie MeSH
- vazba proteinů MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- albuminy MeSH
- antioxidancia MeSH
- antitumorózní látky fytogenní MeSH
- inhibitory cyklooxygenasy MeSH
- inhibitory lipoxygenas MeSH
- lipidy MeSH
- liposomy MeSH
- reaktivní formy kyslíku MeSH
- rostlinné extrakty MeSH
- sérový albumin MeSH
n-3 polyunsaturated fatty acids (PUFA) can exert beneficial effects on glucose homeostasis, especially in obese rodents. Gut incretin hormones regulate glucose and lipid homeostasis, but their involvement in the above effects is not entirely clear. This study aims to assess the effects of chronic n-3 PUFA administration on the insulin and incretin responses in C57BL/6N obese male mice subjected to oral glucose tolerance test (oGTT) after 8 weeks of feeding a corn-oil-based high-fat diet (cHF). The weight gain and adiposity were partially reduced in mice fed cHF in which some of the corn oil was replaced with n-3 PUFA concentrate containing ∼60% DHA and EPA in a 3 : 1 ratio. In addition, these mice had improved glucose tolerance, which was consistent with an increased insulin response to oral glucose and plasma glucagon-like peptide-1 (GLP-1) levels. While the stimulatory effects of n-3 PUFA on GLP-1 levels could not be attributed to changes in intestinal or plasma dipeptidyl peptidase-4 activity, their beneficial effects on glucose tolerance were abolished when mice were pretreated with the GLP-1 receptor antagonist exendin 9-39. Moreover, chronic n-3 PUFA intake prevented the detrimental effects of cHF feeding on glucose-stimulated insulin secretion in the pancreatic islets. Collectively, our data suggest that n-3 PUFA may modulate postprandial glucose metabolism in obese mice through a GLP-1-based mechanism. The significance of these findings in terms of the effective DHA and EPA ratio of the n-3 PUFA concentrate as well as the effect of n-3 PUFA in humans requires further research.
- MeSH
- aplikace orální MeSH
- dieta s vysokým obsahem tuků MeSH
- glukagonu podobný peptid 1 metabolismus MeSH
- glukózový toleranční test MeSH
- homeostáza MeSH
- inzulin metabolismus MeSH
- krevní glukóza metabolismus MeSH
- kyseliny mastné omega-3 aplikace a dávkování MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- přijímání potravy MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- glukagonu podobný peptid 1 MeSH
- inzulin MeSH
- krevní glukóza MeSH
- kyseliny mastné omega-3 MeSH
Essential oils (EOs) of culinary herbs and spices are consumed on a daily basis. They are multicomponent mixtures of compounds with already demonstrated biological activities. Taking into account regular dietary intake and the chemical composition of EOs, they may be considered as candidates for endocrine-disrupting entities. Therefore, we examined the effects of 31 EOs of culinary herbs and spices on transcriptional activities of glucocorticoid receptor (GR), androgen receptor (AR) and vitamin D receptor (VDR). Using reporter gene assays in stably transfected cell lines, weak anti-androgen and anti-glucocorticoid activity was observed for EO of vanilla and nutmeg, respectively. Moderate augmentation of calcitriol-dependent VDR activity was caused by EOs of ginger, thyme, coriander and lemongrass. Mixed anti-glucocorticoid and VDR-stimulatory activities were displayed by EOs of turmeric, oregano, dill, caraway, verveine and spearmint. The remaining 19 EOs were inactive against all receptors under investigation. Analyses of GR, AR and VDR target genes by means of RT-PCR confirmed the VDR-stimulatory effects, but could not confirm the anti-glucocorticoid and anti-androgen effects of EOs. In conclusion, although we observed minor effects of several EOs on transcriptional activities of GR, AR and VDR, the toxicological significance of these effects is very low. Hence, 31 EOs of culinary herbs and spices may be considered safe, in terms of endocrine disruption involving receptors GR, AR and VDR.
- MeSH
- aktivace transkripce účinky léků MeSH
- androgenní receptory chemie metabolismus MeSH
- androgeny škodlivé účinky MeSH
- antagonisté androgenů škodlivé účinky MeSH
- endokrinní disruptory škodlivé účinky MeSH
- jedlé rostliny chemie MeSH
- koření * MeSH
- léčivé rostliny chemie MeSH
- lidé MeSH
- ligandy MeSH
- nádorové buněčné linie MeSH
- oleje prchavé škodlivé účinky MeSH
- receptory glukokortikoidů agonisté antagonisté a inhibitory genetika metabolismus MeSH
- receptory kalcitriolu agonisté antagonisté a inhibitory genetika metabolismus MeSH
- regulace genové exprese účinky léků MeSH
- rekombinantní proteiny chemie metabolismus MeSH
- reportérové geny účinky léků MeSH
- reprodukovatelnost výsledků MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Geografické názvy
- Česká republika MeSH
- Názvy látek
- androgenní receptory MeSH
- androgeny MeSH
- antagonisté androgenů MeSH
- AR protein, human MeSH Prohlížeč
- endokrinní disruptory MeSH
- ligandy MeSH
- oleje prchavé MeSH
- receptory glukokortikoidů MeSH
- receptory kalcitriolu MeSH
- rekombinantní proteiny MeSH
- VDR protein, human MeSH Prohlížeč
Adhesion to the intestinal epithelium is considered an important feature of probiotic bacteria, which may increase their persistence in the intestine, allowing them to exert their beneficial health effect or promote the colonisation process. However, this feature might be largely dependent on the host specificity or diet. In the present study, we investigated the effect of selected milks and milk protein fractions on the ability of selected lactobacilli to adhere to the cells of an intestinal model based on co-culture Caco-2/HT29-MTX cell lines. Most milk digesta did not significantly affect bacterial adhesion except for UHT-treated milk and sheep milk. The presence of UHT-treated milk digesta reduced the adhesion of Lactobacillus gasseri R by 61% but not that of Lactobacillus casei FMP. However, sheep milk significantly increased the adherence of L. casei FMP (P < 0.05) but not of L. gasseri R. Among the protein fractions, rennet casein (RCN) and bovine serum albumin (BSA) showed reproducible patterns and strain-specific effects on bacterial adherence. While RCN reduced the adherence of L. gasseri R to <50% compared to the control, it did not have a significant effect on L. casei FMP. In contrast, BSA reduced L. casei FMP adherence to a higher extent than that of L. gasseri R. Whey protein (WH) tended to increase the adherence of both strains by 130%-180%. Recently, interactions between the host diet and its microbiota have attracted considerable interest. Our results may explain one of the aspects of the role of milk in the development of microbiota or support of probiotic supplements. Based on our data, we conclude that the persistence of probiotic strains supplemented as part of dairy food or constitutional microbiota in the gut might be affected negatively or positively by the food matrix through complex strain or concentration dependent effects.
- MeSH
- bakteriální adheze účinky léků MeSH
- buňky HT-29 MeSH
- Caco-2 buňky MeSH
- epitel účinky léků metabolismus MeSH
- epitelové buňky účinky léků metabolismus MeSH
- hostitelská specificita účinky léků MeSH
- kokultivační techniky MeSH
- Lactobacillus casei účinky léků MeSH
- Lactobacillus gasseri účinky léků MeSH
- lidé MeSH
- mléčné bílkoviny farmakologie MeSH
- mléko chemie mikrobiologie MeSH
- ovce MeSH
- střeva cytologie účinky léků MeSH
- střevní sliznice metabolismus MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- mléčné bílkoviny MeSH
Besides its classical function as an orchestrator of calcium and phosphorus homeostasis, vitamin D also affects insulin secretion and tissue efficiency. A number of studies have consistently reported the inverse relationship between vitamin D deficiency and type 2 diabetes. Activation of certain metabolic pathways and down-stream transcription factors may protect from glucolipotoxicity and their targeted activation -e.g. by vitamin D - might explain the detrimental role of vitamin D deficiency in diabetes. The aim of the study was to quantify gene and protein expression of selected enzymes involved in the protection from glucolipotoxicity, specifically glyoxalase 1 (GLO1), and other enzymes with antioxidant activity - hemoxygenase (HMOX), thiamin pyrophosphokinase (TPK1) and transketolase (TKT), under normo- and hyperglycemic conditions and upon addition of vitamin D in peripheral blood mononuclear cells (PBMCs) and human umbilical vein endothelial cells (HUVEC). The results of our study indicate that the active form of vitamin D regulates gene expression of enzymes opposing the harmful effect of glucolipotoxicity whose activities appear to be suppressed by hyperglycemia. However, we were unable to confirm this effect on protein expression. While we cannot speculate on the effect of vitamin D on diabetes itself our results support its role in the protection against existing glucolipotoxicity therefore possibly translating into the prevention of development of diabetic complications.
- MeSH
- endoteliální buňky pupečníkové žíly (lidské) účinky léků enzymologie MeSH
- homeostáza účinky léků MeSH
- inzulin metabolismus MeSH
- kultivované buňky MeSH
- laktoylglutathionlyasa genetika metabolismus MeSH
- leukocyty mononukleární účinky léků enzymologie MeSH
- lidé MeSH
- regulace genové exprese MeSH
- sekrece inzulinu MeSH
- thiaminpyrofosfokinasa genetika metabolismus MeSH
- transketolasa genetika metabolismus MeSH
- vitamin D farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- GLO1 protein, human MeSH Prohlížeč
- inzulin MeSH
- laktoylglutathionlyasa MeSH
- thiaminpyrofosfokinasa MeSH
- transketolasa MeSH
- vitamin D MeSH
Anthocyans are biologically active constituents of various berry fruits and they are also contained in nutritional supplements derived from extracts or dry matter from berry fruits. In this study we evaluated the effects of anthocyans on the expression of selected drug-metabolizing phase II genes in primary cultures of human hepatocytes by qRT-PCR. Most of the tested anthocyanidins (6) and anthocyanins (21) did not induce the expression of mRNA of UGT1A/2B members in human hepatocytes. The same can be stated for expression of selected GST genes on the mRNA level. However, some of them e.g. cyanidin-3-O-rutinoside consistently decreased the level of GSTP1 mRNA in all tested cultures. In conclusion, most of the anthocyans did not affect the expression of selected phase II metabolizing enzymes in vitro.
- MeSH
- anthokyaniny farmakologie MeSH
- glukuronosyltransferasa genetika metabolismus MeSH
- hepatocyty účinky léků enzymologie metabolismus MeSH
- II. fáze biotransformace * MeSH
- kultivované buňky MeSH
- lidé MeSH
- xenobiotika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- anthokyaniny MeSH
- glukuronosyltransferasa MeSH
- xenobiotika MeSH
Spirulina platensis, a water blue-green alga, has been associated with potent biological effects, which might have important relevance in atheroprotection. We investigated whether S. platensis or phycocyanobilin (PCB), its tetrapyrrolic chromophore, can activate atheroprotective heme oxygenase-1 (Hmox1), a key enzyme in the heme catabolic pathway responsible for generation of a potent antioxidant bilirubin, in endothelial cells and in a mouse model of atherosclerosis. In vitro experiments were performed on EA.hy926 endothelial cells exposed to extracts of S. platensis or PCB. In vivo studies were performed on ApoE-deficient mice fed a cholesterol diet and S. platensis. The effect of these treatments on Hmox1, as well as other markers of oxidative stress and endothelial dysfunction, was then investigated. Both S. platensis and PCB markedly upregulated Hmox1 in vitro, and a substantial overexpression of Hmox1 was found in aortic atherosclerotic lesions of ApoE-deficient mice fed S. platensis. In addition, S. platensis treatment led to a significant increase in Hmox1 promoter activity in the spleens of Hmox-luc transgenic mice. Furthermore, both S. platensis and PCB were able to modulate important markers of oxidative stress and endothelial dysfunction, such as eNOS, p22 NADPH oxidase subunit, and/or VCAM-1. Both S. platensis and PCB activate atheroprotective HMOX1 in endothelial cells and S. platensis increased the expression of Hmox1 in aortic atherosclerotic lesions in ApoE-deficient mice, and also in Hmox-luc transgenic mice beyond the lipid lowering effect. Therefore, activation of HMOX1 and the heme catabolic pathway may represent an important mechanism of this food supplement for the reduction of atherosclerotic disease.
- MeSH
- aorta účinky léků enzymologie MeSH
- ateroskleróza farmakoterapie enzymologie prevence a kontrola MeSH
- cévní buněčněadhezivní molekula-1 genetika metabolismus MeSH
- fykobiliny aplikace a dávkování MeSH
- fykokyanin aplikace a dávkování MeSH
- hemoxygenasa-1 genetika metabolismus MeSH
- lidé MeSH
- myši inbrední C57BL MeSH
- myši transgenní MeSH
- myši MeSH
- NADPH-oxidasy genetika metabolismus MeSH
- oxidační stres účinky léků MeSH
- Spirulina chemie MeSH
- upregulace účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- cévní buněčněadhezivní molekula-1 MeSH
- fykobiliny MeSH
- fykokyanin MeSH
- hemoxygenasa-1 MeSH
- NADPH-oxidasy MeSH
- phycocyanobilin MeSH Prohlížeč
