Inflammatory Bowel Diseases (IBD), e.g. Crohn’s Disease, are disorders with constantly increasing incidence and not completely effective pharmacotherapy. Number of active natural compounds with positive effect in therapy of IBD is intensively studied. Therapeutic synergy between them and glucans - natural saccharides with well-documented immunomodulatory effect - was not tested so far. Glucan microparticles can serve as carriers for biologically active compounds to simplify the administration of water insoluble drugs into organism and to open the possibility of significant amplification of anti-inflammatory effect as well. Based on previous in vivo and clinical trials, chemically diverse natural compounds, which may be encapsulated into glucan particles, were chosen as promising for therapy of chronic inflammatory disorders. The aim of project is to prove via in vitro and in vivo studies the suitability of utilization the glucan microparticles as vectors of these anti-inflammatory compounds in the therapy of IBD and to optimize the composition of glucan-active compound composite.

Nespecifické střevní záněty (např. Crohnova choroba) jsou onemocnění se stále narůstající incidencí, jejichž současná farmakoterapie není zcela efektivní. Existuje ovšem celá řada přírodních aktivních látek s pozitivním vlivem při terapii střevních zánětů, které jsou intenzivně zkoumány. Prozatím ale nebyla testována možná terapeutická synergie mezi těmito látkami a glukany, přírodními sacharidy s dobře zdokumentovaným imunomodulačním účinkem. Glukanové částice mohou sloužit jako nosiče biologicky aktivních látek, což zjednoduší aplikaci ve vodě nerozpustných látek do organismu a zároveň skýtá možnost razantního zesílení protizánětlivého účinku. Na základě předchozích in vivo a klinických studií byly vytipovány chemicky různorodé přírodní látky, které jsou slibné pro terapii chronických zánětlivých onemocnění a lze je enkapsulovat do glukanových částic. Cílem projektu je pomocí in vitro a in vivo studií ověřit, zda je vhodné použít glukanové mikročástice jako nosiče těchto protizánětlivých látek k terapii střevních zánětů a optimalizovat složení kompozitu glukan-aktivní látka.

• MeSH
• antiflogistika MeSH
• biologické faktory MeSH
• glukany terapeutické užití   MeSH
• idiopatické střevní záněty farmakoterapie   MeSH
• intravitální mikroskopie MeSH
• lidé MeSH
• mikropartikule MeSH
• nosiče léků MeSH
• techniky in vitro MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• hodnotící studie MeSH

• Konspekt
• Farmacie. Farmakologie
• NLK Obory
• gastroenterologie
• farmacie a farmakologie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu AZV MZ ČR

The goal of this work was to assess the usability of yeast glucan particles (GPs) as carriers for curcumin and determine the beneficial effect of a pharmacological composite of curcumin in GPs on dextran sulfate sodium induced colitis in rats. The assessment of the anti-inflammatory effect of particular substances was evaluated on the basis of the calculated disease activity index and by assessment of cytokines and enzymes from the gut tissue - tumor necrosis factor α (TNF-α), transforming growth factor β1, interleukin (IL)-1β, IL-6, IL-10, IL-17, catalase, superoxide dismutase 2, myeloperoxidase (MPO), and matrix metalloproteinase 9. Composites of GPs with incorporated curcumin showed promising results with the capability to lower symptoms of colitis and significantly decrease the production of pro-inflammatory cytokines TNF-α, IL-1β, IL-6, and the activity of MPO, as well. The anti-inflammatory effect of the composites was greater than those of pure GPs or curcumin.

• MeSH
• antiflogistika aplikace a dávkování   terapeutické užití   MeSH
• cytokiny metabolismus   MeSH
• glukany aplikace a dávkování   terapeutické užití   MeSH
• interleukiny metabolismus   MeSH
• kolitida chemicky indukované   farmakoterapie   MeSH
• krysa rodu rattus MeSH
• kurkumin aplikace a dávkování   terapeutické užití   MeSH
• nosiče léků terapeutické užití   MeSH
• potkani Wistar MeSH
• Saccharomyces cerevisiae metabolismus   MeSH
• síran dextranu MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

In this work, novel amorphous solid dispersions based on yeast glucan particles were produced. Yeast glucan particles are hollow and porous, and they are mainly composed of amorphous polysaccharides. We hypothesized that these particles are suitable candidates for the amorphization of drugs with low water solubility. Model drugs ibuprofen and curcumin were successfully encapsulated in glucan particles by spray drying. Different spray-drying parameters were tested to evaluate the influence of atomizing droplet size and initial solid content on encapsulation efficiency. It was shown that higher solid content and, more significantly, larger droplet sizes lead to higher encapsulation efficiencies. The encapsulation efficiency of ibuprofen (10 wt%) into glucan particles was considerably improved from 41.3 ± 0.5% to 64.3 ± 0.2% by increasing initial solid content and droplet size with the two-fluid nozzle. The spray drying process was further optimized by using the ultrasonic nozzle and it was possible to achieve complete encapsulation of ibuprofen and curcumin without any precipitation of the active compound outside of the glucan particles. Overall, it was possible to produce completely amorphous composites with outstanding wettability and dispersion properties, and with significantly faster dissolution rates when compared to the micronized crude drug.

• MeSH
• aerosoly MeSH
• beta-glukany chemie   izolace a purifikace   MeSH
• ibuprofen chemie   MeSH
• kinetika MeSH
• kurkumin chemie   MeSH
• nosiče léků * MeSH
• příprava léků MeSH
• rozpustnost MeSH
• Saccharomyces cerevisiae chemie   MeSH
• ultrazvuk * MeSH
• uvolňování léčiv MeSH
• velikost částic MeSH
• vysoušení * MeSH
• Publikační typ
• časopisecké články MeSH

Geranylovaný flavanon diplakon je látka izolovaná z Paulownia tomentosa (Thunb.) Steud. (Paulowniaceae) vykazující protizánětlivé a antioxidační vlastnosti a také vysokou lipofilitu a nízkou rozpustnost ve vodě. Jako modelová molekula byl proto použit k inkorporaci do glukanových částic (GP) s cílem zvýšit jeho potenciální biodostupnost. GP jsou v principu duté schránky připravené čištěním kvasinek Saccharomyces cerevisiae pro získání buněčné stěny, obsahující převážně β-(1→3)/β-(1→6) glukan. Cílem práce je porovnat antiflogistické působení kompozitů diplakonu a glukanového nosiče s působením samotné látky, samotných glukanových částic a fyzické směsi čistých glukanových částic s čistým diplakonem. Na buněčné linii odvozené z lidských leukemických monocytů THP1-XBlueTM-MD2-CD14 byla simulována zánětlivá reakce stimulací buněk lipopolysacharidem (LPS) z Escherichia coli. Kompozity GP a diplakonu signifikantně snížily aktivitu prozánětlivých transkripčních faktorů nukleárního faktoru κB (NF-κB) a aktivátorového proteinu 1 (AP-1) v porovnání s čistou látkou.

Geranylated flavanone diplacone is a flavanone isolated from Paulownia tomentosa (Thunb.) Steud. (Paulowniaceae) with anti-inflammatory and antioxidant properties, nevertheless showing high lipophilicity and low solubility in water. Diplacone was therefore used as a model molecule for incorporation into glucan particles (GPs). GPs are prepared by intensive washing of yeast (Saccharomyces cerevisiae) leading to hollow shells consisting of β-(1→3)/β-(1→6) glucan mainly. The aim of this study was to compare anti-inflammatory potential of GPs-diplacone composites with the compound itself, GPs themselves and the physical mixture of GPs and diplacone. The cell line THP1-XBlueTM-MD2-CD14 derived from human leukemic monocytes was stimulated with lipopolysaccharide (LPS) from Escherichia coli to trigger inflammatory reaction. The composites of GPs with diplacone significantly decreased the activity of pro-inflammatory transcription factors nuclear factor κB (NF-κB) and activator protein 1 (AP-1).

• Klíčová slova
• diplakon,
• MeSH
• enkapsulace buněk MeSH
• glukany terapeutické užití   MeSH
• klinická studie jako téma MeSH
• lidé MeSH
• zánět * farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

Natural compounds offer a wide spectrum of potential active substances, but often they have a poor bioavailability. To increase the bioavailability and bioactivity of the natural anti-inflammatory molecules curcumin and diplacone, we used glucan particles (GPs), hollow shells from Saccharomyces cerevisiae composed mainly of β-1,3-d-glucan. Their indigestibility and relative stability in the gut combined with their immunomodulatory effects makes them promising carriers for such compounds. This study aimed to determine how curcumin and diplacone, either alone or incorporated in GPs, affect the immunomodulatory activity of the latter by assessing the respiratory burst response and the secretion of pro-inflammatory cytokines by primary porcine innate immune cells. Incorporating curcumin and diplacone into GPs by controlled evaporation of the organic solvent substantially reduced the respiratory burst response mediated by GPs. Incorporated curcumin in GPs also reduced GPs mediated secretion of IL-1β and TNF-α by innate immune cells. The obtained results indicate a potentially beneficial effect of the incorporation of curcumin or diplacone into GPs against inflammation.

• MeSH
• antiflogistika chemie   farmakologie   MeSH
• beta-glukany chemie   izolace a purifikace   farmakologie   MeSH
• flavanony chemie   farmakologie   MeSH
• imunologické faktory chemie   izolace a purifikace   farmakologie   MeSH
• interleukin-1beta metabolismus   MeSH
• kultivované buňky MeSH
• kurkumin chemie   farmakologie   MeSH
• leukocyty mononukleární účinky léků   imunologie   metabolismus   MeSH
• neutrofily účinky léků   imunologie   metabolismus   MeSH
• nosiče léků * MeSH
• příprava léků MeSH
• respirační vzplanutí účinky léků   MeSH
• rozpouštědla chemie   MeSH
• Saccharomyces cerevisiae chemie   MeSH
• Sus scrofa MeSH
• TNF-alfa metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Glucan particles derived from yeast have been recently proposed as potential drug delivery carriers. Here, we demonstrate the potential of glucan particles for protein delivery in vivo, using the insect Drosophila melanogaster as a model organism. By employing genetic tools, we demonstrate the capacity of yeast glucan particles to spread efficiently through the Drosophila body, to enter macrophages and to deliver an active transcription factor protein successfully. Moreover, the glucan particles were nontoxic and induced only minimal immune response. The injection of glucan particles did not impair the ability of Drosophila to fight and survive infection by pathogenic bacteria. From this study, Drosophila emerges as an excellent model to test and develop drug delivery systems based on glucan particles, specifically aimed to regulate macrophages.

• MeSH
• Drosophila melanogaster imunologie   metabolismus   MeSH
• glukany chemie   metabolismus   MeSH
• kvasinky chemie   MeSH
• lékové transportní systémy * MeSH
• makrofágy cytologie   imunologie   metabolismus   MeSH
• nosiče léků chemie   metabolismus   MeSH
• proteiny Drosophily chemie   metabolismus   MeSH
• transkripční faktory chemie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Glucan particles (GPs) from Saccharomyces cerevisiae are hollow shells that are composed mainly of β-1,3-d-glucan, which has demonstrated immunomodulatory and anti-inflammatory potential both in vitro and in vivo. Curcumin is a natural hydrophobic phenolic compound, which possesses a significant anti-inflammatory effect and is used as supportive therapy in the treatment of many inflammatory diseases. The aim of this study is to evaluate the possible synergic effect and other benefits of the co-application of GPs and curcumin in the form of pharmaceutical composites. GP/curcumin composites were prepared using controlled evaporation of the organic solvent and their anti-oxidative effect and anti-inflammatory potential were tested on THP1‑XBlue™‑MD2‑CD14 human monocytes cell line. The anti-oxidative effect was measured on pyocyanin-stimulated cells in vitro and the NF-κB/AP-1 signaling pathway on lipopolysaccharide pre-treated monocytes was chosen for anti-inflammatory assays. The secretion of pro-inflammatory cytokines TNF-α and IL-1β was evaluated as well. Results mostly showed a pro-oxidative activity of empty GPs, however, pharmaceutical composites demonstrated an anti-oxidative effect. The activity of NF-κB/AP-1 was substantially decreased by the tested GP/curcumin composites, which also caused the attenuation of cytokines secretion. The obtained results indicate a beneficial effect of the incorporation of curcumin into GPs.

• MeSH
• antiflogistika aplikace a dávkování   chemie   MeSH
• glukany aplikace a dávkování   chemie   MeSH
• interleukin-1beta metabolismus   MeSH
• kurkumin aplikace a dávkování   chemie   MeSH
• lidé MeSH
• lipopolysacharidy MeSH
• makrofágy účinky léků   metabolismus   MeSH
• monocyty účinky léků   metabolismus   MeSH
• NF-kappa B metabolismus   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• Saccharomyces cerevisiae MeSH
• THP-1 buňky MeSH
• TNF-alfa metabolismus   MeSH
• transkripční faktor AP-1 metabolismus   MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Nowadays, there is a continuous need to find new types of the safe drugs. This review deals with various possibilities of application of glucan particles (GP), and emphasizes their advantages when used as carrier for oral vaccination. The trend in research is to develop and im- prove methods of oral vaccination, where the antigen can produce the required immunological responses. Currently, only few vaccines are approved for oral administration. Glucan particles can be used for the stimulation of both humoral and cellular immune response. Substances encapsulated into GP are protected against the harsh environment of the gastrointestinal tract. The particles can be used as a carrier of siRNA and also as a carrier of various kinds of substances like resveratrol.

• MeSH
• beta-glukany * MeSH
• nosiče léků MeSH
• příprava léků metody   MeSH
• vakcíny MeSH
• Publikační typ
• práce podpořená grantem MeSH

Morusin is a prenylated flavonoid isolated from the root bark of Morus alba. Many studies have shown the ability of flavonoids to act as anti-inflammatory agents. The aim of this study was to evaluate the effect of morusin on experimentally colitis induced by 2,4,6-trinitrobenzensulfonic acid in Wistar rats and to compare it with sulfasalazine, a drug conventionally used in the treatment of inflammatory bowel disease. Morusin was administered by gavage at doses of 12.5, 25, or 50 mg/kg/day for five days. The colonic tissue was evaluated macroscopically, histologically, and by performing immunodetection and zymographic analysis to determine the levels of antioxidant enzymes [superoxide dismutase (SOD) and catalase (CAT)], interleukin (IL)-1β, and transforming growth factor (TGF)-β1 and the activities of matrix metalloproteinases (MMP) 2 and 9. The tissue damage scores were significantly reduced with increasing dose of morusin, however efficacy was not demonstrated at the highest dose. At the dose of 12.5 mg/kg, morusin exerted therapeutic effectivity similar to that of sulfasalazine (50 mg/kg). This was associated with significant reduction of TGF-β1 levels and MMP2 and MMP9 activities, and slight reduction of IL-1β. Our results suggest that morusin possesses therapeutic potential for the treatment of chronic inflammatory diseases.

• MeSH
• flavonoidy farmakologie   MeSH
• kolitida chemicky indukované   enzymologie   prevence a kontrola   MeSH
• kolon účinky léků   enzymologie   patologie   MeSH
• kyselina trinitrobenzensulfonová MeSH
• matrixová metaloproteinasa 2 metabolismus   MeSH
• potkani Wistar MeSH
• prenylace MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Geranyl flavones have been studied as compounds that potentially can be developed as anti-inflammatory agents. A series of natural geranylated flavanones was isolated from Paulownia tomentosa fruits, and these compounds were studied for their anti-inflammatory activity and possible mechanism of action. Two new compounds were characterized [paulownione C (17) and tomentodiplacone O (20)], and all of the isolated derivatives were assayed for their ability to inhibit cyclooxygenases (COX-1 and COX-2) and 5-lipoxygenase (5-LOX). The compounds tested showed variable degrees of activity, with several of them showing activity comparable to or greater than the standards used in COX-1, COX-2, and 5-LOX assays. However, only the compound tomentodiplacone O (20) showed more selectivity against COX-2 versus COX-1 when compared with ibuprofen. The ability of the test compounds to interact with the above-mentioned enzymes was supported by docking studies, which revealed the possible incorporation of selected test substances into the active sites of these enzymes. Furthermore, one of the COX/LOX dual inhibitors, diplacone (14) (a major geranylated flavanone of P. tomentosa), was studied in vitro to obtain a proteomic overview of its effect on inflammation in LPS-treated THP-1 macrophages, supporting its previously observed anti-inflammatory activity and revealing the mechanism of its anti-inflammatory effect.

• MeSH
• antiflogistika chemie   izolace a purifikace   farmakologie   MeSH
• arachidonát-5-lipoxygenasa metabolismus   MeSH
• cyklooxygenasa 1 metabolismus   MeSH
• cyklooxygenasa 2 metabolismus   MeSH
• flavonoidy chemie   izolace a purifikace   farmakologie   MeSH
• inhibitory cyklooxygenasy 2 chemie   izolace a purifikace   farmakologie   MeSH
• inhibitory lipoxygenas chemie   izolace a purifikace   farmakologie   MeSH
• Magnoliopsida chemie   MeSH
• molekulární struktura MeSH
• ovoce chemie   MeSH
• proteomika * MeSH
• Publikační typ
• časopisecké články MeSH