BACKGROUND AND PURPOSE: Radiation-induced intestinal injury (RIII) compromises the clinical utility of pelvic radiotherapy (RT). We aimed to explore the protective effect and underlying mechanism of (-)-epigallocatechin-3-gallate (EGCG) on RIII. MATERIALS AND METHODS: We evaluated the protective effect of EGCG on intestine in RIII mouse model and pelvic cancer patients, while explored the underlying mechanism through (1) 16S rRNA sequencing, (2) metabolomic profiles, (3) fresh sterile fecal filtrate (SFF) transplantation, and (4) transcriptome sequencing. RESULTS: EGCG efficiently prevented RIII in mouse, as reflected by improved survival, alleviated intestinal structure damage, promoted intestinal regeneration, and ameliorated gut microbiota dysbiosis. Prophylactic EGCG intervention reduced the severity of RIII in patients receiving pelvic RT. Mechanistically, the protective effect of EGCG could be transferred to other mice by SFF transplantation. EGCG enriched gut microbiota-derived metabolite D-tagatose, and oral administration of D-tagatose reproduced the radio-protective effect of EGCG via activating AMPK. CONCLUSION: Oral EGCG may be a promising strategy for preventing RIII clinically, and warrant further investigation in prospective randomized phase III trials.
- MeSH
- katechin * analogy a deriváty farmakologie MeSH
- lidé MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nádory pánve * radioterapie MeSH
- proteinkinasy aktivované AMP metabolismus MeSH
- radiační poranění * prevence a kontrola MeSH
- radioprotektivní látky farmakologie terapeutické užití MeSH
- střeva účinky záření účinky léků mikrobiologie MeSH
- střevní mikroflóra * účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Maintenance of NAD pools is critical for neuronal survival. The capacity to maintain NAD pools declines in neurodegenerative disease. We identify that low NMNAT2, the critical neuronal NAD producing enzyme, drives retinal susceptibility to neurodegenerative insults. As proof of concept, gene therapy over-expressing full length human NMNAT2 is neuroprotective. To pharmacologically target NMNAT2, we identify that epigallocatechin gallate (EGCG) can drive NAD production in neurons through an NMNAT2 and NMN dependent mechanism. We confirm this by pharmacological and genetic inhibition of the NAD-salvage pathway. EGCG is neuroprotective in rodent (mixed sex) and human models of retinal neurodegeneration. As EGCG has poor drug-like qualities, we use it as a tool compound to generate novel small molecules which drive neuronal NAD production and provide neuroprotection. This class of NMNAT2 targeted small molecules could have an important therapeutic impact for neurodegenerative disease following further drug development.
- MeSH
- genetická terapie metody MeSH
- katechin * analogy a deriváty farmakologie MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- NAD * metabolismus MeSH
- neurodegenerativní nemoci farmakoterapie metabolismus genetika MeSH
- neurony * metabolismus účinky léků MeSH
- neuroprotektivní látky * farmakologie MeSH
- nikotinamidnukleotidadenylyltransferasa * metabolismus genetika MeSH
- retina metabolismus účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví 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
Clostridium perfringens forms biofilms and spores that are a source of food contamination. In this study, the antibacterial activities of Lactobacillus plantarum culture supernatants (LP-S), LP-S fractions, and the plant-derived compound epigallocatechin gallate (EG) were evaluated. Specifically, their effects on the viability and biofilm-forming ability of C. perfringens were assessed. Moreover, the expression of quorum sensing-regulated genes associated with the pathogenesis of this microorganism and that of genes involved in biofilm formation was also investigated. The results showed that both EG and the LP-S exerted bactericidal activity against all C. perfringens strains tested. The minimal bactericidal concentration (MBC) of EG was 75 µg/mL for all strains but ranged from 61 to 121 µg of total protein per mL for LP-S. EG exerted only minor effects on biofilm formation, whereas LP-S, particularly its 10 and 30 K fractions, significantly reduced the biofilm-forming ability of all the strains. The antibiofilm activity of LP-S was lost following preincubation with proteases, suggesting that it was mediated by a proteinaceous molecule. The treatment of C. perfringens with either EG or LP-S did not change the transcript levels of two CpAL (C. perfringens quorum-sensing Agr-like system)-related genes, agrB and agrD, which are known to be involved in the regulation of biofilms, suggesting that LP-S exerted its biofilm inhibitory activity downstream of CpAL signaling. In summary, we demonstrated the bactericidal activity of EG and LP-S against C. perfringens and antibiofilm activity of LP-S at a subinhibitory dose. Our results suggested that these compounds can be further explored for food safety applications to control agents such as C. perfringens.
The aim of present study was to evaluate the action of green tea and its constituents on rabbit ovarian functions and some non-reproductive indexes. In in vitro experiments, rabbit ovarian fragments were cultured with green tea constituents - epigallocatechin-3-gallate (EGCG), green tea polyphenols (GTPP) and resveratrol (RSV) (at 0, 1, 10 or 100 μg/mL medium). The accumulation of an apoptosis marker - caspase 3 and the release of progesterone (P4) and testosterone (T) were measured. In in vivo experiments, does were fed a standard diet or a diet enriched with green tea powder. The weight gain, mortality, ovarian length and weight, conception and kindling rate, number of liveborn, stillborn, and weaned pups, diameter of ovarian follicles and some blood haematological and biochemical parameters were analysed. Culture of ovarian fragments with EGCG increased accumulation of caspase 3, whilst both GTTP and RSV decreased it. EGCG inhibited both P4 and T output, GTPP stimulated P4 and inhibited T, whilst RSV promoted release of both P4 and T. Feeding with green tea increased ovarian length and diameter of ovarian non-ovulated peri-ovulatory haemorrhagic but not of primary and secondary growing follicles. Furthermore, green tea reduced conception and kindling rate, the number of liveborn and weaned pups, increased female mortality but not their weight gain. It reduced platelet distribution width, but it did not affect other haematological and biochemical indexes. These observations suggest that dietary green tea can reduce rabbit doe's viability, ovarian functions and fecundity, perhaps due to changes in ovarian cell apoptosis, steroid hormones release and blockade of the ovulation of large ovarian follicles. The anti-reproductive action of green tea could be due to its constituent - EGCG with pro-apoptotic and anti-steroid hormone properties.
- MeSH
- apoptóza MeSH
- čaj chemie MeSH
- fertilita účinky léků MeSH
- kaspasa 3 metabolismus MeSH
- katechin analogy a deriváty izolace a purifikace farmakologie MeSH
- králíci * MeSH
- ovarium účinky léků metabolismus MeSH
- polyfenoly izolace a purifikace farmakologie MeSH
- resveratrol izolace a purifikace farmakologie MeSH
- zvířata MeSH
- Check Tag
- králíci * MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Polyphenols are known for their antimicrobial activity, whilst both polyphenols and the globular protein β-lactoglobulin (bLG) are suggested to have antioxidant properties and promote cell proliferation. These are potentially useful properties for a tissue-engineered construct, though it is unknown if they are retained when both compounds are used in combination. In this study, a range of different microbes and an osteoblast-like cell line (human fetal osteoblast, hFOB) were used to assess the combined effect of: (1) green tea extract (GTE), rich in the polyphenol epigallocatechin gallate (EGCG), and (2) whey protein isolate (WPI), rich in bLG. It was shown that approximately 20-48% of the EGCG in GTE reacted with WPI. GTE inhibited the growth of Gram-positive bacteria, an effect which was potentiated by the addition of WPI. GTE alone also significantly inhibited the growth of hFOB cells after 1, 4, and 7 days of culture. Alternatively, WPI significantly promoted hFOB cell growth in the absence of GTE and attenuated the effect of GTE at low concentrations (64 µg/mL) after 4 and 7 days. Low concentrations of WPI (50 µg/mL) also promoted the expression of the early osteogenic marker alkaline phosphatase (ALP) by hFOB cells, whereas GTE inhibited ALP activity. Therefore, the antioxidant effects of GTE can be boosted by WPI, but GTE is not suitable to be used as part of a tissue-engineered construct due to its cytotoxic effects which negate any positive effect WPI has on cell proliferation.
- MeSH
- antibakteriální látky chemie farmakologie MeSH
- antioxidancia chemie farmakologie MeSH
- Bacteria účinky léků MeSH
- buněčná diferenciace účinky léků MeSH
- buněčné linie MeSH
- čaj chemie MeSH
- dospělí MeSH
- fibroblasty cytologie účinky léků MeSH
- katechin analogy a deriváty chemie farmakologie MeSH
- kultivované buňky MeSH
- lidé MeSH
- mladý dospělý MeSH
- osteoblasty cytologie účinky léků MeSH
- osteogeneze účinky léků MeSH
- polyfenoly chemie farmakologie MeSH
- proliferace buněk účinky léků MeSH
- syrovátkové proteiny chemie farmakologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Spinal cord injury (SCI) is a debilitating condition which is characterized by an extended secondary injury due to the presence of inflammatory local milieu. Epigallocatechin gallate (EGCG) appears to possess strong neuroprotective properties. Here, we evaluated the beneficial effect of EGCG on recovery from SCI. Male Wistar rats were given either EGCG or saline directly to the injured spinal cord and thereafter a daily IP injection. Behavior recovery was monitored by BBB, plantar, rotarod and flat-beam tests. The levels of inflammatory cytokines were determined on days 1, 3, 7, 10 and 14 after SCI. Additionally, NF-κB pathway activity was evaluated. The results demonstrated that EGCG-treated rats displayed a superior behavioral performance in a flat beam test, higher axonal sprouting and positive remodelation of glial scar. Cytokine analysis revealed a reduction in IL-6, IL2, MIP1α and RANTES levels on days 1 and 3, and an upregulation of IL-4, IL-12p70 and TNFα 1 day following SCI in EGCG-treated rats. Treatment with EGCG was effective in decreasing the nuclear translocation of subunit p65 (RelA) of the NF-κB dimer, and therefore canonical NF-κB pathway attenuation. A significant increase in the gene expression of growth factors (FGF2 and VEGF), was noted in the spinal cord of EGCG-treated rats. Further, EGCG influenced expression of M1 and M2 macrophage markers. Our results have demonstrated a therapeutic value of EGCG in SCI, as observed by better behavioral performance measured by flat beam test, modulation of inflammatory cytokines and induction of higher axonal sprouting.
- MeSH
- axony účinky léků MeSH
- čaj chemie MeSH
- chování zvířat účinky léků MeSH
- cytokiny metabolismus MeSH
- katechin aplikace a dávkování analogy a deriváty MeSH
- mediátory zánětu metabolismus MeSH
- myelitida komplikace metabolismus MeSH
- neuroprotektivní látky aplikace a dávkování MeSH
- NF-kappa B metabolismus MeSH
- poranění míchy komplikace metabolismus patologie prevence a kontrola MeSH
- potkani Wistar MeSH
- regenerace nervu účinky léků MeSH
- signální transdukce účinky léků MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Polyphenols form one of the largest groups of natural compounds and possess a wide range of biological properties. These activities can be influenced by the galloyl moiety within their structures. A multitude of galloylated polyphenolic compounds occurs in nature, but galloylated phenols are also produced synthetically to influence their biological properties. This review provides a comprehensive summary of current knowledge about natural (galloylated catechins, theaflavins and proanthocyanidins, penta-O-galloyl-β-d-glucose, gallotannins, ellagitannins, ellagic acid and flavonols) and semisynthetic gallates with a focus on their biological activity and toxicity issues. The effects of tea catechins (epicatechin, epigallocatechin, epicatechin gallate, and epigallocatechin gallate) and semisynthetic galloyl esters of the flavonolignans silybin and 2,3-dehydrosilybin from the milk thistle (Silybum marianum) on angiogenesis were used as examples of the structure-activity relationship (SAR) study.
- MeSH
- katechin analogy a deriváty chemie farmakologie MeSH
- lidé MeSH
- polyfenoly chemie farmakologie MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Epigallocatechin gallate (EGCG) is a green tea antioxidant with adverse effects on rat liver mitochondria and hepatocytes at high doses. Here, we assessed whether low doses of EGCG would protect these systems from damage induced by tert-butyl hydroperoxide (tBHP). Rat liver mitochondria or permeabilized rat hepatocytes were pretreated with EGCG and then exposed to tBHP. Oxygen consumption, mitochondrial membrane potential (MMP), and mitochondrial retention capacity for calcium were measured. First, 50 μM EGCG or 0.25 mM tBHP alone increased State 4 Complex I-driven respiration, thus demonstrating uncoupling effects; tBHP also inhibited State 3 ADP-stimulated respiration. Then, the coexposure to 0.25 mM tBHP and 50 μM EGCG induced a trend of further decline in the respiratory control ratio beyond that observed upon tBHP exposure alone. EGCG had no effect on MMP and no effect, in concentrations up to 50 μM, on mitochondrial calcium retention capacity. tBHP led to a decline in both MMP and mitochondrial retention capacity for calcium; these effects were not changed by pretreatment with EGCG. In addition, EGCG dose-dependently enhanced hydrogen peroxide formation in a cell- and mitochondria-free medium. Conclusion. Moderate nontoxic doses of EGCG were not able to protect rat liver mitochondria and hepatocytes from tBHP-induced mitochondrial dysfunction.
- MeSH
- hepatocyty cytologie účinky léků metabolismus MeSH
- jaterní mitochondrie účinky léků metabolismus MeSH
- katechin analogy a deriváty farmakologie MeSH
- krysa rodu rattus MeSH
- kultivované buňky MeSH
- membránový potenciál mitochondrií účinky léků MeSH
- peroxid vodíku metabolismus MeSH
- potkani Wistar MeSH
- spotřeba kyslíku účinky léků MeSH
- terc-butylhydroperoxid toxicita MeSH
- vápník metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The knowledge of processes in intestinal cells is essential, as most xenobiotics come into contact with the small intestine first. Caco-2 cells are human colorectal adenocarcinoma that once differentiated, exhibit enterocyte-like characteristics. Our study compares activities and expressions of important conjugation enzymes and their modulation by green tea extract (GTE) and epigallocatechin gallate (EGCG) using both proliferating (P) and differentiated (D) caco-2 cells. The mRNA levels of the main conjugation enzymes were significantly elevated after the differentiation of Caco-2 cells. However, no increase in conjugation enzymes' activities in differentiated cells was detected in comparison to proliferating ones. GTE/EGCG treatment did not affect the mRNA levels of any of the conjugation enzymes tested in either type of cells. Concerning conjugation enzymes activities, GTE/EGCG treatment elevated glutathione S-transferase (GST) activity by approx. 30% and inhibited catechol-O-methyltransferase (COMT) activity by approx. 20% in differentiated cells. On the other hand, GTE as well as EGCG treatment did not significantly affect the activities of conjugation enzymes in proliferating cells. Administration of GTE/EGCG mediated only mild changes of GST and COMT activities in enterocyte-like cells, indicating a low risk of GTE/EGCG interactions with concomitantly administered drugs. However, a considerable chemo-protective effect of GTE via the pronounced induction of detoxifying enzymes cannot be expected as well.
- MeSH
- buněčná diferenciace účinky léků MeSH
- Caco-2 buňky MeSH
- čaj chemie MeSH
- glutathiontransferasa biosyntéza MeSH
- katechin analogy a deriváty chemie farmakologie MeSH
- katechol-O-methyltransferasa biosyntéza MeSH
- lidé MeSH
- messenger RNA biosyntéza MeSH
- proliferace buněk účinky léků MeSH
- regulace genové exprese enzymů účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
