indole Dotaz Zobrazit nápovědu
- MeSH
- indoly analýza metabolismus MeSH
- lidé MeSH
- melaniny chemie metabolismus MeSH
- melanom moč MeSH
- referenční hodnoty MeSH
- vysokoúčinná kapalinová chromatografie metody normy přístrojové vybavení MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- srovnávací studie MeSH
Indol-3-karbinol je fytochemická látka získaná z kapustovitých rastlín. Po jeho konzumácii v kyslom prostredí žalúdka vznikajú viaceré oligomerické zložky s rôznou biologickou účinnosťou, medzi nimi aj 3,3 ́-diindolylmetán. Vyznačujú sa antiestrogénovou a antiproliferačnou aktivitou. Štúdie priniesli pozitívne výsledky pri skúmaní efektu indol-3-karbinolu a jeho metabolitu 3,3 ́-diindolylmetánu v súvislosti s rôznymi onkologickými ochoreniami, pri dysplastických léziach cervixu, vulvárnej intraepiteliálnej neoplázii, či bunkách karcinómu prsníka. Priaznivým ovplyvnením metabolizmu estrogénov, metabolizmu glukózy a znížením inzulínovej rezistencie sa zdá byť nádejnou doplnkovou liečbou pri syndróme polycystických ovárií, či iných hormonálnych poruchách. Užívanie indol-3-karbinolu sa považuje za bezpečné, bez výskytu závažných nežiadúcich účinkov. Cieľom článku bolo zhrnúť aktuálne poznatky účinku indol-3-karbinolu a jeho metabolitov.
Indole-3-carbinol is a phytochemical derived from cruciferous vegetables. After its consumption, in acidic enviroment of stomach, several oligomeric components with different biological activity are formed, inclu-ding 3,3 ́-diindolylmethane. They are characterized by antiestrogen and antiproliferative activity. Studies have shown positive results in investigating the effect of indole-3-carbinol and its metabolite 3,3 ́-diindolylmetha-ne in connection with various oncological diseases, in dysplastic lesions of the cervix, vulvar intraepithelial neoplasia, or breast cancer cells. By favorably influencing estrogen metabolism, glucose metabolism and re-ducing insulin resistance, it appears to be a promising complementary treatment for polycystic ovarian syn-drome or other hormonal disorders. The use of indole-3-carbinol is considered safe, without the occurrence of serious side effects. The aim of the article was to summarize the current knowledge of the effect of indo-le-3-carbinol and its metabolites.
- Klíčová slova
- Indol-3-karbinol, 3,3-diindolmetan,
- MeSH
- indoly * terapeutické užití MeSH
- lidé MeSH
- nádory prsu terapie MeSH
- nádory vulvy terapie MeSH
- prekancerózy terapie MeSH
- syndrom polycystických ovarií terapie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
Glycosides of benzodioxole-indole alkaloid 6-hydroxy-galanthindole (7-(6'-(hydroxymethyl)benzo[d][1',3']dioxol-5'-yl)-1-methyl-1H-indol-6-ol) having axial chirality were isolated from Narcissus cultivar 'Dutch Master'. The structure, including absolute configuration, was determined by means of extensive spectroscopic data such as UV, IR, CD, MS, 1D and 2D NMR spectra, and computational chiroptical methods. The aglycone has a structure containing two aromatic moieties with substituents hindering rotation about the biaryl axis and is connected to a saccharide moiety linked at C-6 and made up of one, two, or three sugars (glucose, alpha-L-rhamnopyranosyl-(1-->6)-beta-D-glucopyranose, and trisaccharide ([beta-D-xylopyranosyl(1-->2)]-[alpha-L-rhamnopyranosyl-(1-->6)]-beta-D-glucopyranose).
- MeSH
- alkaloidy amarylkovitých chemie MeSH
- benzodioxoly chemie izolace a purifikace MeSH
- glykosidy chemie izolace a purifikace MeSH
- indolové alkaloidy chemie izolace a purifikace MeSH
- molekulární struktura MeSH
- Narcissus chemie MeSH
- rostlinné extrakty chemie MeSH
- sacharidy MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Glyoxyl analogs of indole phytoalexins brassinin, 1-methoxybrassinin, brassitin, 1-methoxybrassitin and 1-methoxybrassenin B were prepared, using (1H-indol-3-yl)-, (1-methoxyindol-3-yl)- and [1-(2,3,4,6-tetra-O-acetyl-ß-D-glucopyranosyl)indol-3-yl]glyoxyl chlorides as starting compounds. Synthesized products were examined for their antiproliferative activity against human cancer cell lines Jurkat (T-cell acute lymphoblastic leukemia), MCF-7 (breast adenocarcinoma, estrogen receptor-positive), MDA-MB-231 (breast adenocarcinoma, estrogen receptor-negative), HeLa (cervical adenocarcinoma), CCRF-CEM cell line (T-cell acute lymphoblastic leukemia) and A-549 cell line (lung adenocarcinoma), and their activity compared with natural phytoalexins and corresponding (1H-indol-3-yl)acetic acid derivatives. The highest potency with IC50 3.3–66.1 µmol l–1 was found for glyoxyl analogs of 1-methoxybrassenin B.
Gastrointestinal microbes respond to biochemical metabolites that coordinate their behaviors. Here, we demonstrate that bacterial indole functions as a multifactorial mitigator of Klebsiella grimontii and Klebsiella oxytoca pathogenicity. These closely related microbes produce the enterotoxins tilimycin and tilivalline; cytotoxin-producing strains are the causative agent of antibiotic-associated hemorrhagic colitis and have been associated with necrotizing enterocolitis of premature infants. We demonstrate that carbohydrates induce cytotoxin synthesis while concurrently repressing indole biosynthesis. Conversely, indole represses cytotoxin production. In both cases, the alterations stemmed from differential transcription of npsA and npsB, key genes involved in tilimycin biosynthesis. Indole also enhances conversion of tilimycin to tilivalline, an indole analog with reduced cytotoxicity. In this context, we established that tilivalline, but not tilimycin, is a strong agonist of pregnane X receptor (PXR), a master regulator of xenobiotic detoxification and intestinal inflammation. Tilivalline binding upregulated PXR-responsive detoxifying genes and inhibited tubulin-directed toxicity. Bacterial indole, therefore, acts in a multifunctional manner to mitigate cytotoxicity by Klebsiella spp.: suppression of toxin production, enhanced conversion of tilimycin to tilivalline, and activation of PXR. IMPORTANCE The human gut harbors a complex community of microbes, including several species and strains that could be commensals or pathogens depending on context. The specific environmental conditions under which a resident microbe changes its relationship with a host and adopts pathogenic behaviors, in many cases, remain poorly understood. Here, we describe a novel communication network involving the regulation of K. grimontii and K. oxytoca enterotoxicity. Bacterial indole was identified as a central modulator of these colitogenic microbes by suppressing bacterial toxin (tilimycin) synthesis and converting tilimycin to tilivalline while simultaneously activating a host receptor, PXR, as a means of mitigating tissue cytotoxicity. On the other hand, fermentable carbohydrates were found to inhibit indole biosynthesis and enhance toxin production. This integrated network involving microbial, host, and metabolic factors provides a contextual framework to better understand K. oxytoca complex pathogenicity.
- MeSH
- cytotoxiny metabolismus MeSH
- enterotoxiny metabolismus MeSH
- indoly metabolismus MeSH
- infekce bakteriemi rodu Klebsiella * mikrobiologie MeSH
- Klebsiella oxytoca genetika metabolismus MeSH
- lidé MeSH
- novorozenec MeSH
- pseudomembranózní enterokolitida * mikrobiologie MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
The aryl hydrocarbon receptor (AhR), deemed initially as a xenobiotic sensor, plays multiple physiological roles and is involved in various pathophysiological processes and many diseases' etiology. Therefore, the therapeutic and chemopreventive targeting of AhR is a fundamental issue. To date, thousands of structurally diverse ligands of AhR have been identified. The bottleneck in targeting the AhR is that it is a Janus-faced player with beneficial vs. harmful effects in the ligand-specific context. A distinct structural class of the AhR ligands is those with indole-based scaffolds. The present review summarizes the knowledge on the existing indole-derived AhR ligands, comprising natural and dietary compounds, synthetic compounds including clinically used drugs, endogenous intermediary metabolites, and catabolites produced by human microbiota. The examples of novel, indole ring containing, rational design based AhR ligands are presented. The molecular, in vitro, and in vivo effects are described.
