pinostilbene Dotaz Zobrazit nápovědu
Stilbenoids are dietary phenolics with notable biological effects on humans. Epidemiological, clinical, and nutritional studies from recent years have confirmed the significant biological effects of stilbenoids, such as oxidative stress protection and the prevention of degenerative diseases, including cancer, cardiovascular diseases, and neurodegenerative diseases. Stilbenoids are intensively metabolically transformed by colon microbiota, and their corresponding metabolites might show different or stronger biological activity than their parent molecules. The aim of the present study was to determine the metabolism of six stilbenoids (resveratrol, oxyresveratrol, piceatannol, thunalbene, batatasin III, and pinostilbene), mediated by colon microbiota. Stilbenoids were fermented in an in vitro faecal fermentation system using fresh faeces from five different donors as an inoculum. The samples of metabolized stilbenoids were collected at 0, 2, 4, 8, 24, and 48 h. Significant differences in the microbial transformation among stilbene derivatives were observed by liquid chromatography mass spectrometry (LC/MS). Four stilbenoids (resveratrol, oxyresveratrol, piceatannol and thunalbene) were metabolically transformed by double bond reduction, dihydroxylation, and demethylation, while batatasin III and pinostilbene were stable under conditions simulating the colon environment. Strong inter-individual differences in speed, intensity, and pathways of metabolism were observed among the faecal samples obtained from the donors.
- MeSH
- chromatografie kapalinová MeSH
- feces mikrobiologie MeSH
- fenoly chemie metabolismus MeSH
- fermentace MeSH
- hmotnostní spektrometrie MeSH
- kolon metabolismus mikrobiologie MeSH
- lidé MeSH
- mikrobiota * MeSH
- resveratrol chemie metabolismus MeSH
- stilbeny chemie metabolismus MeSH
- tandemová hmotnostní spektrometrie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Staphylococcus aureus is a major human pathogen that is responsible for both hospital- and community-acquired infections. Stilbenes are polyphenol compounds of plant origin known to possess a variety of pharmacological properties, such as antibacterial, antiviral, and antifungal effects. This study reports the in vitro growth-inhibitory potential of eight naturally occurring stilbenes against six standard strains and two clinical isolates of S. aureus, using a broth microdilution method, and expressing the results as minimum inhibitory concentrations (MICs). Pterostilbene (MICs = 32-128 μg/ml), piceatannol (MICs = 64-256 μg/ml), and pinostilbene (MICs = 128 μg/ml) are among the active compounds that possess the strongest activity against all microorganisms tested, followed by 3'-hydroxypterostilbene, isorhapontigenin, oxyresveratrol, and rhapontigenin with MICs 128-256 μg/ml. Resveratrol (MIC = 256 μg/ml) exhibited only weak inhibitory effect. Furthermore, structure-activity relationships were studied. Hydroxyl groups at ortho-position (B-3' and -4') played crucial roles for the inhibitory effect of hydroxystilbene piceatannol. Compounds with methoxy groups at ring A (3'-hydroxypterostilbene, pinostilbene, and pterostilbene) produced stronger effect against S. aureus than their analogues (isorhapontigenin and rhapontigenin) with methoxy groups at ring B. These findings provide arguments for further investigation of stilbenes as prospective leading structures for development of novel antistaphylococcal agents for topical treatment of skin infections.
- MeSH
- antibakteriální látky chemie farmakologie MeSH
- fytonutrienty chemie farmakologie MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- stafylokokové infekce mikrobiologie MeSH
- Staphylococcus aureus účinky léků izolace a purifikace MeSH
- stilbeny chemie farmakologie MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Natural polyphenol resveratrol (trihydroxystilbene) is a partial agonist of human aryl hydrocarbon receptor AhR, thereby, displaying a plethora of biological effects. Biological activities of metoxylated and hydroxylated stilbenes were studied in the past. The aim of the current study was to describe the effects of 13 different hydroxy- and methoxystilbenes, including their cis/trans isomers on the transcriptional activity of AhR and the expression of CYP1A genes in hepatic cancer cells HepG2 and in primary human hepatocytes. Techniques of gene reporter assays, qRT-PCR, Simple Western blotting by Sally Sue™ and electrophoretic mobility shift assay EMSA were employed. All compounds activated AhR, but their efficacies, potencies and dose-response profiles differed substantially. The strongest activators of AhR and inducers of CYP1A1 in HepG2 cells were DMU-212 ((E)-3,4,5,4´-tetramethoxystilbene), trans-piceatannol, cis-piceatannol, trans-trismethoxyresveratrol and trans-pinostilbene. While DMU-212 and trans-trismethoxyresveratrol also induced CYP1A1 and CYP1A2 in primary human hepatocytes, the effects of trans-piceatannol, cis-piceatannol and trans-pinostilbene weaned off. On the other hand, trans-4-methoxystilbene was strong CYP1A inducer in hepatocytes but not in HepG2 cells. Differences between effects of stilbenes in HepG2 cells and human hepatocytes are probably due to the extensive phase I and phase II xenobiotic metabolism in human hepatocytes. The data obtained may be of toxicological relevance.
- MeSH
- buňky Hep G2 účinky léků MeSH
- cytochrom P-450 CYP1A1 genetika MeSH
- cytochrom P-450 CYP1A2 genetika MeSH
- dospělí MeSH
- hepatocyty účinky léků MeSH
- induktory cytochromu P450 CYP1A2 chemie farmakologie MeSH
- isomerie MeSH
- kultivované buňky MeSH
- lidé středního věku MeSH
- lidé MeSH
- receptory aromatických uhlovodíků genetika metabolismus MeSH
- regulace genové exprese účinky léků MeSH
- senioři MeSH
- stilbeny chemie farmakologie MeSH
- transkripční faktory bHLH genetika metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
Resveratrol (RSV) is a stilbene phytochemical common in food and red wine. RSV inhibits cytochrome P450 CYP3A4 activity and interacts with the pregnane X receptor (PXR), the central regulator of drug/xenobiotic metabolizing enzyme expression. In this work, we comprehensively examined the effects of 13 stilbenes (trans- and cis-resveratrol, trans- and cis-piceatannol, oxyresveratrol, pterostilbene, pinostilbene, a,b-dihydroresveratrol, trans- and cis-trismethoxyresveratrol, trans-3,4,5,4'-tetramethoxystilbene, trans-2,4,3',5'-tetramethoxystilbene, trans-4-methoxystilbene), on CYP3A4 and CYP2B6 mRNA induction, and on CYP3A4/5, CYP2C8/9/19, CYP2D6, CYP2A6, CYP2E1, CYP1A2 and CYP2B6 cytochrome P450 enzyme activities. Expression experiments in five different primary human hepatocyte preparations, reporter gene assays, and ligand binding assays with pregnane X (PXR) and constitutive androstane (CAR) receptors were performed. Inhibition of cytochrome P450 enzymes was examined in human microsomes. We found that only polymethoxylated stilbenes are prone to significantly induce CYP2B6 or CYP3A4 in primary human hepatocytes via pregnane X receptor (PXR) interaction. Natural resveratrol derivatives such as trans- and cis-RSV, oxyresveratrol, pinostilbene and pterostilbene significantly inhibit CYP3A4/5 enzymatic activities; however, only trans-RSV significantly inhibits CYP3A4/5 activity (both testosterone 6β-hydroxylation and midazolam 1´-hydroxylation) in micromolar concentrations by a non-competitive mechanism, suggesting a potential risk of food-drug interactions with CYP3A4/5 substrates.
- MeSH
- hepatocyty účinky léků MeSH
- inhibitory cytochromu P450 metabolismus MeSH
- interakce mezi potravou a léky * MeSH
- kultivované buňky MeSH
- lidé MeSH
- resveratrol MeSH
- steroidní receptory metabolismus MeSH
- stilbeny metabolismus farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Dietary phenolics or polyphenols are mostly metabolized by the human gut microbiota. These metabolites appear to confer the beneficial health effects attributed to phenolics. Microbial composition affects the type of metabolites produced. Reciprocally, phenolics modulate microbial composition. Understanding this relationship could be used to positively impact health by phenolic supplementation and thus create favorable colonic conditions. This study explored the effect of six stilbenoids (batatasin III, oxyresveratrol, piceatannol, pinostilbene, resveratrol, thunalbene) on the gut microbiota composition. Stilbenoids were anaerobically fermented with fecal bacteria from four donors, samples were collected at 0 and 24 h, and effects on the microbiota were assessed by 16S rRNA gene sequencing. Statistical tests identified affected microbes at three taxonomic levels. Observed microbial composition modulation by stilbenoids included a decrease in the Firmicutes to Bacteroidetes ratio, a decrease in the relative abundance of strains from the genus Clostridium, and effects on the family Lachnospiraceae. A frequently observed effect was a further decrease of the relative abundance when compared to the control. An opposite effect to the control was observed for Faecalibacterium prausnitzii, whose relative abundance increased. Observed effects were more frequently attributed to resveratrol and piceatannol, followed by thunalbene and batatasin III.
The stilbenoids, a group of naturally occurring phenolic compounds, are found in a variety of plants, including some berries that are used as food or for medicinal purposes. They are known to be beneficial for human health as anti-inflammatory, chemopreventive, and antioxidative agents. We have investigated a group of 19 stilbenoid substances in vitro using a cellular model of THP-1 macrophage-like cells and pyocyanin-induced oxidative stress to evaluate their antioxidant or pro-oxidant properties. Then we have determined any effects that they might have on the expression of the enzymes catalase, glutathione peroxidase, and heme oxygenase-1, and their effects on the activation of Nrf2. The experimental results showed that these stilbenoids could affect the formation of reactive oxygen species in a cellular model, producing either an antioxidative or pro-oxidative effect, depending on the structure pinostilbene (2) worked as a pro-oxidant and also decreased expression of catalase in the cell culture. Piceatannol (4) had shown reactive oxygen species (ROS) scavenging activity, whereas isorhapontigenin (18) had a mild direct antioxidant effect and activated Nrf2-antioxidant response element (ARE) system and elevated expression of Nrf2 and catalase. Their effects shown on cells in vitro warrant their further study in vivo.
- MeSH
- antioxidační responzivní elementy účinky léků MeSH
- antioxidancia chemie farmakologie MeSH
- buňky Hep G2 MeSH
- faktor 2 související s NF-E2 genetika MeSH
- lidé MeSH
- peroxidace lipidů účinky léků MeSH
- pyokyanin chemie MeSH
- stilbeny chemie farmakologie MeSH
- thiobarbituráty chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
