Diabetes is closely connected with skeletal muscle dysfunction. Ellagic acid (EA) possesses a variety of bio-effects and is applied to the improvement of diabetes. The purpose of this study was to explore the potential improvement effect and mechanisms of EA in streptozotocin (STZ)-induced diabetic muscle atrophy. The model of diabetic mice was established by intra-peritoneal STZ to evaluate treatment effect of EA (100 mg/kg/d for 8 weeks) on muscle atrophy. Our data exhibited that EA enhanced fiber size and weight of gastrocnemius, and promoted grip strength to relieve STZ-induced muscle lesions. In serum, the levels of Creatine kinase (CK), lactate dehydrogenase (LDH), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL) were inhibited, while high-density lipoprotein cholesterol (HDL) level was enhanced by EA treatment in diabetic mice. In gastrocnemius, EA decreased Atrogin-1 and MuRF-1 expressions to relieve STZ-induced muscle atrophy. Moreover, EA increased NRF-1 and PGC-1alpha expressions to alleviate mitochondrial disorder. Meanwhile, EA suppressed CHOP and GRP-87 levels to relieve ER stress. Lastly, EA inhibited BAX expressions and enhanced Bcl-2 expressions to mitigate apoptosis. In conclusion, EA is preventing the event of STZ-induced gastrocnemia by amelioration of mitochondrial dysfunction, ER stress and apoptosis, and could be used in the protection and therapeutic of muscle atrophy in diabetes.
- MeSH
- cholesterol metabolismus MeSH
- experimentální diabetes mellitus * chemicky indukované komplikace farmakoterapie MeSH
- kosterní svaly metabolismus MeSH
- kyselina ellagová * farmakologie terapeutické užití metabolismus MeSH
- myši MeSH
- streptozocin metabolismus farmakologie MeSH
- svalová atrofie farmakoterapie prevence a kontrola metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Yeast glucan particles (GPs) are promising agents for the delivery of biologically active compounds as drugs. GPs possess their own biological activities and can act synergistically with their cargo. This study aimed to determine how incorporating artemisinin, ellagic acid, (-)-epigallocatechin gallate, morusin, or trans-resveratrol into GPs affects their anti-inflammatory and antioxidant potential in vitro. Two different methods - slurry evaporation and spray drying - were used to prepare composites (GPs + bioactive compound) and the anti-inflammatory and antioxidative properties of the resultant products were compared. Several of the natural compounds showed the beneficial effects of being combined with GPs. The materials prepared by spray drying showed greater activity than those made using a rotary evaporator. Natural compounds incorporated into yeast GPs showed greater anti-inflammatory potential in vitro than simple suspensions of these compounds as demonstrated by their inhibition of the activity of transcription factors NF-κB/AP-1 and the secretion of the pro-inflammatory cytokine TNF-α.
- MeSH
- antiflogistika farmakologie MeSH
- antioxidancia farmakologie MeSH
- artemisininy farmakologie MeSH
- cytokiny MeSH
- flavonoidy chemie farmakologie MeSH
- glukany chemie farmakologie MeSH
- katechin analogy a deriváty chemie farmakologie MeSH
- kyselina ellagová chemie farmakologie MeSH
- monocyty účinky léků MeSH
- NF-kappa B MeSH
- resveratrol chemie farmakologie MeSH
- Saccharomyces cerevisiae - proteiny MeSH
- Saccharomyces cerevisiae MeSH
- Publikační typ
- časopisecké články MeSH
The aim of this publication is to compile a summary of the findings regarding punicalagin in various tissues described thus far in the literature, with an emphasis on the effect of this substance on immune reactions. Punicalagin (PUN) is an ellagitannin found in the peel of pomegranate (Punica granatum). It is a polyphenol with proven antioxidant, hepatoprotective, anti-atherosclerotic and chemopreventive activities, antiproliferative activity against tumor cells; it inhibits inflammatory pathways and the action of toxic substances, and is highly tolerated. This work describes the source, metabolism, functions and effects of punicalagin, its derivatives and metabolites. Furthermore, its anti-inflammatory and antioxidant effects are described.
- MeSH
- antiflogistika farmakologie MeSH
- biologická dostupnost MeSH
- hydrolyzovatelné taniny imunologie metabolismus MeSH
- imunosupresiva farmakologie MeSH
- kyselina ellagová analýza MeSH
- lidé MeSH
- metabolom MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Ellagic acid, a natural substance found in various fruits and nuts, was previously shown to exhibit beneficial effects towards metabolic syndrome. In this study, using a genetic rat model of metabolic syndrome, we aimed to further specify metabolic and transcriptomic responses to ellagic acid treatment. Adult male rats of the SHR-Zbtb16Lx/k.o. strain were fed a high-fat diet accompanied by daily intragastric gavage of ellagic acid (50 mg/kg body weight; high-fat diet-ellagic acid (HFD-EA) rats) or vehicle only (high-fat diet-control (HFD-CTL) rats). Morphometric and metabolic parameters, along with transcriptomic profile of liver and brown and epididymal adipose tissues, were assessed. HFD-EA rats showed higher relative weight of brown adipose tissue (BAT) and decreased weight of epididymal adipose tissue, although no change in total body weight was observed. Glucose area under the curve, serum insulin, and cholesterol levels, as well as the level of oxidative stress, were significantly lower in HFD-EA rats. The most differentially expressed transcripts reflecting the shift induced by ellagic acid were detected in BAT, showing downregulation of BAT activation markers Dio2 and Nr4a1 and upregulation of insulin-sensitizing gene Pla2g2a. Ellagic acid may provide a useful nutritional supplement to ameliorate features of metabolic syndrome, possibly by suppressing oxidative stress and its effects on brown adipose tissue.
- MeSH
- biologické markery analýza MeSH
- dieta s vysokým obsahem tuků MeSH
- epididymis MeSH
- hnědá tuková tkáň chemie MeSH
- játra chemie MeSH
- krevní glukóza analýza MeSH
- krysa rodu rattus MeSH
- kyselina ellagová aplikace a dávkování MeSH
- messenger RNA analýza MeSH
- metabolický syndrom genetika metabolismus prevence a kontrola MeSH
- oxidační stres účinky léků MeSH
- potkani inbrední SHR MeSH
- RNA analýza MeSH
- transkriptom účinky léků MeSH
- tuková tkáň chemie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
In Italy a particularly valuable chestnut is "Marrone di Roccadaspide", a protected geographical indication (PGI) product, deriving from a Castanea sativa cultivar, typical of Salerno province in Campania region. As chestnut industrial processes yield a large amount of shell by-products, in this study the possibility to retrain this waste food as potential source of bioactives was investigated. The ability of "Marrone di Roccadaspide" shell MeOH extract to modulate the pro-inflammatory transcriptional factor NF-κB after LPS stimulation, along with the antioxidant activity by a cell-based in vitro test, were evaluated. To correlate the NF-κB inhibition (67.67% at 5 μg/mL) and the strong antioxidant activity to the chemical composition, an analytical approach based on LC-ESI/LTQOrbitrap/MS/MSn along with NMR characterization of isolated compounds was developed. The identification of hydrolysable and condensed tannins, along with flavonoids, phenol glucosides, ellagic acid derivatives, and triterpenoids was accomplished. The most representative compounds were quantitatively analyzed by LC-ESI/QTrap/MS/MS, showing bartogenic acid as the compound occurring in the highest amount (103.08 mg/100 g shells). With the aim to explore the possibility to employ chestnut shells as suitable source of bioactives for the preparation of functional ingredients, the chemical composition and the antioxidant activity of "eco-friendly" extracts (EtOH and EtOH:H2O 7:3) was finally evaluated, showing a high superimposability of the EtOH:H2O (7:3) extract to the MeOH extract.
- MeSH
- antioxidancia analýza MeSH
- Fagaceae chemie MeSH
- fenoly analýza MeSH
- flavonoidy analýza MeSH
- glukosidy analýza MeSH
- hodnotící studie jako téma MeSH
- hydrolyzovatelné taniny analýza MeSH
- kalibrace MeSH
- kyselina ellagová analýza MeSH
- lidé MeSH
- NF-kappa B metabolismus MeSH
- ořechy chemie MeSH
- proantokyanidiny analýza MeSH
- proliferace buněk MeSH
- racionalizace * MeSH
- reaktivní formy kyslíku MeSH
- rostlinné extrakty analýza MeSH
- tandemová hmotnostní spektrometrie MeSH
- taniny analýza MeSH
- triterpeny analýza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Itálie MeSH
CARM1 interacts with numerous transcription factors to mediate cellular processes, especially gene expression. This is important for the maintenance of ESC pluripotency or intervention to tumorigenesis. Here, we studied epigenomic effects of two potential CARM1 modulators: an activator (EML159) and an inhibitor (ellagic acid dihydrate, EA). We examined nuclear morphology in human and mouse embryonic stem cells (hESCs, mESCs), as well as in iPS cells. The CARM1 modulators did not function similarly in all cell types. EA decreased the levels of the pluripotency markers, OCT4 and NANOG, particularly in iPSCs, whereas the levels of these proteins increased after EML159 treatment. EML159 treatment of mouse ESCs led to decreased levels of OCT4 and NANOG, which was accompanied by an increased level of Endo-A. The same trend was observed for NANOG and Endo-A in hESCs affected by EML159. Interestingly, EA mainly changed epigenetic features of nucleoli because a high level of arginine asymmetric di-methylation in the nucleoli of hESCs was reduced after EA treatment. ChIP-PCR of ribosomal genes confirmed significantly reduced levels of H3R17me2a, in both the promoter region of ribosomal genes and rDNA encoding 28S rRNA, after EA addition. Moreover, EA treatment changed the nuclear pattern of AgNORs (silver-stained nucleolus organizer regions) in all cell types studied. In EA-treated ESCs, AgNOR pattern was similar to the pattern of AgNORs after inhibition of RNA pol I by actinomycin D. Together, inhibitory effect of EA on arginine methylation and effect on related morphological parameters was especially observed in compartment of nucleoli.
- MeSH
- buněčné jadérko účinky léků fyziologie ultrastruktura MeSH
- buněčné linie MeSH
- embryonální kmenové buňky účinky léků fyziologie ultrastruktura MeSH
- epigeneze genetická účinky léků fyziologie MeSH
- kyselina ellagová farmakologie MeSH
- lidé MeSH
- myši MeSH
- proteinarginin-N-methyltransferasy antagonisté a inhibitory fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
We studied the effect of ellagic acid (EA) on the morphology of nucleoli and on the pattern of major proteins of the nucleolus. After EA treatment of HeLa cells, we observed condensation of nucleoli as documented by the pattern of argyrophilic nucleolar organizer regions (AgNORs). EA also induced condensation of RPA194-positive nucleolar regions, but no morphological changes were observed in nucleolar compartments positive for UBF1/2 proteins or fibrillarin. Studied morphological changes induced by EA were compared with the morphology of control, non-treated cells and with pronounced condensation of all nucleolar domains caused by actinomycin D (ACT-D) treatment. Similarly as ACT-D, but in a lesser extent, EA induced an increased number of 53BP1-positive DNA lesions. However, the main marker of DNA lesions, γH2AX, was not accumulated in body-like nuclear structures. An increased level of γH2AX was found by immunofluorescence and Western blots only after EA treatment. Intriguingly, the levels of fibrillarin, UBF1/2 and γH2AX were increased at the promoters of ribosomal genes, while 53BP1 and CARM1 levels were decreased by EA treatment at these genomic regions. In the entire genome, EA reduced H3R17 dimethylation. Taken together, ellagic acid is capable of significantly changing the nucleolar morphology and protein levels inside the nucleolus.
- MeSH
- buněčné dělení účinky léků MeSH
- buněčné jadérko chemie účinky léků ultrastruktura MeSH
- chromozomální proteiny, nehistonové analýza MeSH
- daktinomycin farmakologie MeSH
- epigeneze genetická účinky léků MeSH
- G2 fáze účinky léků MeSH
- guanylátcyklasa analýza antagonisté a inhibitory MeSH
- HeLa buňky chemie účinky léků MeSH
- histony analýza metabolismus MeSH
- intracelulární signální peptidy a proteiny analýza MeSH
- kyselina ellagová farmakologie MeSH
- lidé MeSH
- metylace MeSH
- nádorové proteiny analýza MeSH
- organizátor jadérka chemie účinky léků ultrastruktura MeSH
- poškození DNA MeSH
- posttranslační úpravy proteinů účinky léků MeSH
- promotorové oblasti (genetika) MeSH
- ribozomální DNA účinky léků genetika MeSH
- RNA-polymerasa I analýza MeSH
- signální adaptorové proteiny CARD analýza antagonisté a inhibitory MeSH
- transkripční iniciační komplex Pol1 - proteiny analýza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Rod Bergenia z čeledi Saxifragaceae patří mezi zajímavý zdroj léčivých látek. Na celém světě je známo kolem 30 druhů bergenií. Vědecké zkoumání je v současnosti zaměřeno na pět druhů rostoucích v horských oblastech střední a východní Asie: Bergenia ciliata (Haw.) Sternb., Bergenia stracheyi Engl., Bergenia crassifolia (L.) Fritsch, Bergenia ligulata (Wall.) Engl. a Bergenia himalaica Boriss. Tyto taxony patří mezi nejvíce využívané rostliny v tradiční čínské, nepálské a indické medicíně, kde se používají na léčbu kašle a plicních onemocnění, k zástavě krvácení, při oslabení imunity a k rozpouštění ledvinových nebo močových kamenů. Bergenia obsahuje mnoho aktivních složek zahrnujících bergenin, jeho derivát norbergenin, katechin, kyselinu gallovou, arbutin a další třísloviny. U nás je tato rostlina běžně pěstována, ale není prozatím využívána k terapeutickým účelům. Extrakty z různých částí rostliny vykazují zajímavou biologickou aktivitu, především antibakteriální, antivirovou, cytoprotektivní a antioxidační.
Bergenia, a genus included in the family Saxifragaceae, is a valuable source of healing matters. About 30 Bergenia species are known all over the world. Scientific research is focused on five species mainly distributed in the mountains of Central and East Asia: Bergenia ciliata (Haw.) Sternb., Bergenia stracheyi Engl., Bergenia crassifolia (L.) Fritsch, Bergenia ligulata (Wall.) Engl. and Bergenia himalaica Boriss. These taxons belong to the widely used medicinal herbs in the traditional Chinese, Nepalese and Indian medicine, for therapy of cough and pulmonary diseases, to stop bleeding, to increase immunity and to dissolve kidney or bladder stones. Bergenia consists of many different active compounds including bergenin, norbergenin, catechin, gallic acid, arbutin and other polyphenols. In the Czech Republic this species is commonly grown but it is not used for medical therapy. Individual parts of this plant demonstrate an interesting biological activity, and antibacterial, antiviral, cytoprotective and antioxidant effects.
- MeSH
- antibakteriální látky MeSH
- antioxidancia MeSH
- antivirové látky MeSH
- arbutin * analogy a deriváty chemie terapeutické užití MeSH
- chemické techniky analytické * metody využití MeSH
- imunologické faktory MeSH
- katechin chemie terapeutické užití MeSH
- kyselina ellagová chemie terapeutické užití MeSH
- lidé MeSH
- Saxifragaceae MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
Pomocí Amesova testu a in vivo mikronukleus testu jsme sledovali antigenotoxický efekt kyseliny elagové (EA) na genotoxicitu tří mutagenů: amino-methylimidazo-chinolinu (IQ), aflatoxinu B1 (AFB1) a N-nitroso-N-methylurey (MNU). Kyselina elagová je fenolová sloučenina, přirozeně se vyskytující v různých druzích ovoce a zeleniny. Její efekt na imunosupresivní aktivitu mutagenů jsme rovněž sledovali in vivo chemiluminescenčním testem. V Amesově testu kyselina elagová v koncentracích 300 a 30 μg na misku prokazatelně inhibovala mutagenní aktivitu dvou nepřímých mutagenů IQ a AFB1. Koncentrace 300 μg na misku měla nejsilnější efekt na mutagenitu všech koncentrací IQ v testech na kmeni TA98 Salmonella typhimurium, zatímco na kmeni TA100 byla koncentrace 30 mg na misku efektivnější než koncentrace 300 μg na misku. Také v kombinaci s různými koncentracemi AFB1 se kyselina elagová chovala jako silný antimutagen. V tomto případě však nižší ze dvou účinných koncentrací – 30 μg na misku měla mnohem větší antimutagenní efekt než koncentrace 300 μg na misku na obou kmenech. V kombinaci s přímým mutagenem MNU nevykazovala kyselina elagová významný antimutagenní efekt ve většině koncentrací testovaných na kmeni TA100. Jenom nejvyšší koncentrace kyseliny elagové redukovala mutagenitu MNU slabě, a to pouze v kombinaci se dvěma nižšími koncentracemi MNU. V mikronukleus testu, třídenní p.o. aplikace kyseliny elagové předcházející aplikaci AFB1, IQ nebo MNU významně redukovala počty mikrojader indukované samotnými mutageny v polychromatofilních erytrocytech myší. Chemiluminescenční test na myších granulocytech prokázal, že kyselina elagová nejen zabraňuje inhibičnímu účinku mutagenů na tvorbu volných kyslíkových radikálů a peroxidu vodíku, ale jejich tvorbu v kombinaci s mutageny stimuluje dokonce ve vyšším rozsahu, než je stimulace samotnou kyselinou elagovou. Z těchto výsledků vyvozujeme, že kyselina elagová silně reparuje imunosupresivní efekt testovaných mutagenů.
Using the Ames bacterial mutagenicity test and an in vivo micronucleus test, we investigated the antigenotoxic effect of ellagic acid on the genotoxicity of three mutagens: amino-methylimidazo-quinoline (IQ), aflatoxin B1 (AFB1), and N-nitroso-N-methylurea (MNU). Ellagic acid is a naturally occurring phenolic compound which is found in a variety of soft fruits and vegetables. The effect of this compound on the immunosuppressive activity of mutagens was followed in vivo by the chemiluminescence test. In the Ames assay, ellagic acid at concentrations of 300 and 30 μg/plate demonstrably inhibits the mutagenic activity of two indirect mutagens: IQ and AFB1. The concentration of 300 μg/plate had the strongest effect on mutagenicity of all concentrations of IQ in strain TA98 of Salmonella typhimurium, whereas in strain TA100 concentration of 30 μg per dish of ellagic acid was more effective than 300 μg per plate. Also in combination with different concentrations of AFB1, ellagic acid proved to be a strong antimutagen. In this case the lower of the two effective concentrations – 30 μg/plate – had a much greater antimutagenic effect on both strains tested than 300 μg/plate. In combination with the direct mutagen MNU, ellagic acid did not show any marked antimutagenic effect at most of the concentrations tested in strain TA100. Only the highest concentrations of ellagic acid reduced the mutagenic effect of MNU weakly and only in combination with two lower concentrations of MNU. In the micronucleus test, three-day oral application of ellagic acid prior to the applicaton of AFB1, IQ, or MNU, respectively, markedly reduced the numbers of micronuclei induced by these three mutagens in polychromatophilic erythrocytes of mice. Chemiluminescence test with mouse granulocytes proved that ellagic acid not only prevents the inhibitory effects of mutagens on free oxygen radicals and hydrogen peroxide production, but that this production is stimulated by ellagic acid in combination with mutagens even to a greater extent than by ellagic acid alone. From these results we can deduce that ellagic acid repairs strong immunosuppressive effects of all mutagens applied.
- MeSH
- aflatoxin B1 analogy a deriváty MeSH
- antimutagenní látky * analýza MeSH
- erytrocyty imunologie MeSH
- imunosupresivní léčba MeSH
- kyselina ellagová * MeSH
- lidé MeSH
- luminiscence MeSH
- methylnitrosomočovina * MeSH
- mikrojaderné testy MeSH
- mutageny * MeSH
- myši inbrední BALB C MeSH
- Salmonella typhimurium MeSH
- statistika jako téma MeSH
- testy genotoxicity MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
