The antioxidant activity of Scorzonera parviflora Jacq. roots were assessed by measuring their ability to scavenge ABTS and DPPH radicals. Bioactivity-guided fractionation was utilized to identify the compound(s) responsible for this activity. The most active phase, ethyl acetate, was isolated using column chromatography. The resulting fractions were then purified using preparative TLC on reverse phase and semi-preparative HPLC. The structures of the pure compounds were elucidated by spectral analysis (MS and 1H, 13C, 2D-NMR). Three undescribed phenolic acid derivatives, namely parvifloric acid A (1), B (2), and C (3), and one new sesquiterpene lactone, parviflorin (4) together with seven known compounds were isolated and identified as scopolin (5), scopoletin (6), caffeic acid (7), protocatechuic acid (8), 4,5-O-dicaffeoylquinic acid (9) 3,5-O-dicaffeoylquinic acid (10), and 3,5-O-dicaffeoylquinic acid methyl ester (11). Finally, the pure compounds obtained were tested to evaluate their antioxidant capacities, using ABTS and DPPH radical scavenging potencies. The highest activity was observed with 3,5-O-dicaffeoylquinic acid (10), followed by its methyl ester.
- MeSH
- antioxidancia * farmakologie izolace a purifikace chemie MeSH
- fytonutrienty farmakologie izolace a purifikace MeSH
- hydroxybenzoáty * izolace a purifikace farmakologie chemie MeSH
- kořeny rostlin * chemie MeSH
- molekulární struktura MeSH
- Scorzonera * chemie MeSH
- seskviterpeny farmakologie izolace a purifikace chemie MeSH
- Publikační typ
- časopisecké články MeSH
A sesquiterpenic alkaloid dendrobine is the major bioactive compound extracted from Dendrobium nobile Lindl. This compound was structurally very similar to picrotoxinin (neurotoxin) containing bicyclic or tricyclic ring while dendrobine containing tetracyclic rings with up to 7 stereogenic centers showing numerous neuroprotective effects. Several sesquiterpenic alkaloids such as (+)-(1R,5R,6S,8R,9R)- 8,12-dihydroxy-copacamphan-3-en-2-one, dendrobine, denrine B, (+)- (1R,2S,3R,4S,5R,6S,9R)-3,11,12-trihydroxypicrotoxane-2(15)-lactone, dendroxine B, nobilonine, 13-Hydroxy-14-oxodendrobine, 6-Hydroxy-nobilonine and (-)-(1S,2R,3S,4R,5S,6R,9S,12R)- 3,11,13-trihydroxypicrotoxane-2(15)-lactone were isolated from D. nobile This comprehensive review summarizes the necessary information on the morphology, biochemistry and pharmacology of dendrobine. The phytochemical profile had potent in-vivo and in-vitro efficacy in neuroprotection, nerve function, memory enhancement, cognitive disorders, anxiety and depression, anti-oxidant, psychological conditions, increasing serotonin concentration in synapse anxiolytic, tranquilizing, anti-stress, neurodegenerative (Alzheimer's disease and Parkinson), anti-inflammatory and analgesic. The compound dendrobine activates neuro synapses, serotonergic synapse and signaling pathways during neurotransmission playing important role in Alzheimer's disease, Parkinson's disease, anxiety and long-term depression.
- MeSH
- alkaloidy * chemie farmakologie izolace a purifikace MeSH
- lidé MeSH
- neurodegenerativní nemoci farmakoterapie MeSH
- neuroprotektivní látky * farmakologie chemie izolace a purifikace MeSH
- seskviterpeny * chemie farmakologie izolace a purifikace MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
CD8+ T cells are essential for adaptive immunity against infection and tumors. Their ability to proliferate after stimulation is crucial to their functionality. Dendritic cells (DCs) are professional antigen-presenting cells that induce their proliferation. Here, we show that thapsigargin-induced LAD2 mast cell (MC) line-released products can impair the ability of monocyte-derived DCs to induce CD8+ T-cell proliferation and the generation of Th1 cytokine-producing T cells. We found that culture medium conditioned with LAD2 MCs previously stimulated with thapsigargin (thapsLAD2) induces maturation of DCs as determined by the maturation markers CD80, CD83, CD86, and HLA-DR. However, thapsLAD2-matured DCs produced no detectable TNFα or IL-12 during the maturation. In addition, although their surface expression of PD-L1 was comparable with the immature or TLR7/8-agonist (R848)-matured DCs, their TIM-3 expression was significantly higher than in immature DCs and even much higher than in R848-matured DCs. In addition, contrary to R848-matured DCs, the thapsLAD2-matured DCs only tended to induce enhanced proliferation of CD4+ T cells than immature DCs. For CD8+ T cells, this tendency was not even detected because thapsLAD2-matured and immature DCs comparably induced their proliferation, which contrasted with the significantly enhanced proliferation induced by R848-matured DCs. Furthermore, these differences were comparably recapitulated in the ability of the tested DCs to induce IFNγ- and IFNγ/TNFα-producing T cells. These findings show a novel mechanism of MC-mediated regulation of adaptive immune responses.
- MeSH
- aktivace lymfocytů * účinky léků imunologie MeSH
- buněčná diferenciace * účinky léků MeSH
- buněčné linie MeSH
- buněčný receptor 2 viru hepatitidy A metabolismus MeSH
- CD8-pozitivní T-lymfocyty * imunologie účinky léků MeSH
- cytokiny metabolismus MeSH
- dendritické buňky * imunologie účinky léků metabolismus MeSH
- imidazoly farmakologie MeSH
- lidé MeSH
- mastocyty * imunologie účinky léků metabolismus MeSH
- monocyty imunologie účinky léků metabolismus MeSH
- proliferace buněk * účinky léků MeSH
- thapsigargin * farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Deoxynivalenol (DON), a potent mycotoxin, exhibits strong immunotoxicity and poses a significant threat to human and animal health. Cell senescence has been implicated in the immunomodulatory effects of DON; however, the potential of DON to induce cell senescence remains inadequately explored. Emerging evidence suggests that hypoxia-inducible factor-1α (HIF-1α) serves as a crucial target of mycotoxins and is closely involved in cell senescence. To investigate this potential, we employed the RAW264.7 macrophage model and treated the cells with varying concentrations of DON (2-8 μM) for 24 h. Transcriptome analysis revealed that 2365 genes were significantly upregulation while 2405 genes were significantly decreased after exposure to DON. KEGG pathway enrichment analysis demonstrated substantial enrichment in pathways associated with cellular senescence and hypoxia. Remarkably, we observed a rapid and sustained increase in HIF-1α expression following DON treatment. DON induced cell senescence through the activation of the p53/p21WAF1/CIP1 (p21) and p16INK4A (p16) pathways, while also upregulating the expression of nuclear factor-κB, leading to the secretion of senescence-associated secretory phenotype (SASP) factors, including IL-6, IL-8, and CCL2. Crucially, HIF-1α positively regulated the expression of p53, p21, and p16, as well as the secretion of SASP factors. Additionally, DON induced cell cycle arrest at the S phase, enhanced the activity of the senescence biomarker senescence-associated β-galactosidase, and disrupted cell morphology, characterized by mitochondrial damage. Our study elucidates that DON induces cell senescence in RAW264.7 macrophages by modulating the HIF-1α/p53/p21 pathway. These findings provide valuable insights for the accurate prevention of DON-induced immunotoxicity and associated diseases.
- MeSH
- faktor 1 indukovatelný hypoxií - podjednotka alfa * metabolismus genetika MeSH
- inhibitor p21 cyklin-dependentní kinasy * metabolismus genetika MeSH
- makrofágy * účinky léků metabolismus MeSH
- myši MeSH
- nádorový supresorový protein p53 * metabolismus MeSH
- RAW 264.7 buňky MeSH
- signální transdukce * účinky léků MeSH
- stárnutí buněk * účinky léků MeSH
- trichotheceny * toxicita MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
As one of the most common mycotoxins, deoxynivalenol (DON) can contaminate a wide range of crops and foods. Porcine circovirus 2 (PCV2) is a kind of immunosuppressive virus, which can cause porcine circovirus associated disease (PCVD) in pig farms infected with PCV2. Pigs are extremely sensitive to DON, and PCV2-infected pig farms are often contaminated with DON. Our previous studies indicated that Bacillus amyloliquefaciens B10 (B10) has the potential to alleviate the toxicity of mycotoxins. The research was aimed at investigating the effects of Bacillus amyloliquefaciens B10 on the immunosuppressive effects caused by both DON and PCV2 infection. The results indicated that the expression of the PCV2 capsid protein CAP was significantly decreased after pretreatment with Bacillus amyloliquefaciens B10. Then, the effects of the Bacillus amyloliquefaciens B10 pretreatment on the type I interferon, antiviral protein and the antiviral signal pathway cGAS-STING was further investigated. The findings displayed that the expression of the type I interferon and antiviral protein were increased, while the IL-10 were decreased after pretreatment with Bacillus amyloliquefaciens B10. The inhibition of DON on the cGAS-STING signal pathway was relieved. Furthermore, it was found that this intervention effect was produced by inhibiting autophagy. In summary, Bacillus amyloliquefaciens B10 can mitigate the immunosuppressive effects of PCV2 and DON by inhibiting the production of autophagy.
BACKGROUND: Malaria in the first trimester of pregnancy is associated with adverse pregnancy outcomes. Artemisinin-based combination therapies (ACTs) are a highly effective, first-line treatment for uncomplicated Plasmodium falciparum malaria, except in the first trimester of pregnancy, when quinine with clindamycin is recommended due to concerns about the potential embryotoxicity of artemisinins. We compared adverse pregnancy outcomes after artemisinin-based treatment (ABT) versus non-ABTs in the first trimester of pregnancy. METHODS: For this systematic review and individual patient data (IPD) meta-analysis, we searched MEDLINE, Embase, and the Malaria in Pregnancy Library for prospective cohort studies published between Nov 1, 2015, and Dec 21, 2021, containing data on outcomes of pregnancies exposed to ABT and non-ABT in the first trimester. The results of this search were added to those of a previous systematic review that included publications published up until November, 2015. We included pregnancies enrolled before the pregnancy outcome was known. We excluded pregnancies with missing estimated gestational age or exposure information, multiple gestation pregnancies, and if the fetus was confirmed to be unviable before antimalarial treatment. The primary endpoint was adverse pregnancy outcome, defined as a composite of either miscarriage, stillbirth, or major congenital anomalies. A one-stage IPD meta-analysis was done by use of shared-frailty Cox models. This study is registered with PROSPERO, number CRD42015032371. FINDINGS: We identified seven eligible studies that included 12 cohorts. All 12 cohorts contributed IPD, including 34 178 pregnancies, 737 with confirmed first-trimester exposure to ABTs and 1076 with confirmed first-trimester exposure to non-ABTs. Adverse pregnancy outcomes occurred in 42 (5·7%) of 736 ABT-exposed pregnancies compared with 96 (8·9%) of 1074 non-ABT-exposed pregnancies in the first trimester (adjusted hazard ratio [aHR] 0·71, 95% CI 0·49-1·03). Similar results were seen for the individual components of miscarriage (aHR=0·74, 0·47-1·17), stillbirth (aHR=0·71, 0·32-1·57), and major congenital anomalies (aHR=0·60, 0·13-2·87). The risk of adverse pregnancy outcomes was lower with artemether-lumefantrine than with oral quinine in the first trimester of pregnancy (25 [4·8%] of 524 vs 84 [9·2%] of 915; aHR 0·58, 0·36-0·92). INTERPRETATION: We found no evidence of embryotoxicity or teratogenicity based on the risk of miscarriage, stillbirth, or major congenital anomalies associated with ABT during the first trimester of pregnancy. Given that treatment with artemether-lumefantrine was associated with fewer adverse pregnancy outcomes than quinine, and because of the known superior tolerability and antimalarial effectiveness of ACTs, artemether-lumefantrine should be considered the preferred treatment for uncomplicated P falciparum malaria in the first trimester. If artemether-lumefantrine is unavailable, other ACTs (except artesunate-sulfadoxine-pyrimethamine) should be preferred to quinine. Continued active pharmacovigilance is warranted. FUNDING: Medicines for Malaria Venture, WHO, and the Worldwide Antimalarial Resistance Network funded by the Bill & Melinda Gates Foundation.
- MeSH
- antimalarika * škodlivé účinky MeSH
- artemether terapeutické užití MeSH
- chinin škodlivé účinky MeSH
- ethanolaminy terapeutické užití MeSH
- fixní kombinace léků MeSH
- kombinace léků artemether a lumefantrin terapeutické užití MeSH
- lidé MeSH
- malárie * farmakoterapie MeSH
- narození mrtvého plodu epidemiologie MeSH
- prospektivní studie MeSH
- první trimestr těhotenství MeSH
- samovolný potrat * MeSH
- těhotenství MeSH
- tropická malárie * farmakoterapie MeSH
- výsledek těhotenství MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
- systematický přehled MeSH
The type B trichothecenes pollute food crops and have been associated to alimentary toxicosis resulted in emetic reaction in human and animal. This group of mycotoxins consists deoxynivalenol (DON) and four structurally related congeners: 3-acetyl-deoxynivalenol (3-ADON), 15-acetyl deoxynivalenol (15-ADON), nivalenol (NIV) and 4-acetyl-nivalenol (fusarenon X, FX). While emesis induced by intraperitoneally dosed to DON in the mink has been related to plasma up-grading of 5-hydroxytryptamine (5-HT) and neurotransmitters peptide YY (PYY), the impact of oral dosing with DON or its four congeners on secretion of these chemical substances have not been established. The aim of this work was to contraste emetic influence to type B trichothecene mycotoxins by orally dosing and involve these influence to PYY and 5-HT. All five toxins attracted marked emetic reaction that are relevant to elevated PYY and 5-HT. The reduction in vomiting induced by the five toxins and PYY was due to blocking of the neuropeptide Y2 receptor. The inhibition of the induced vomiting response by 5-HT and all five toxins is regulated by the 5-HT3 receptor inhibitor granisetron. In a word, our results indicate that PYY and 5-HT take a key role in the emetic reaction evoked by type B trichothecenes.
- MeSH
- emetika škodlivé účinky MeSH
- lidé MeSH
- mykotoxiny * škodlivé účinky MeSH
- norek MeSH
- peptid YY MeSH
- serotonin MeSH
- trichotheceny typu B * škodlivé účinky MeSH
- trichotheceny * toxicita MeSH
- zvířata MeSH
- zvracení chemicky indukované MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: The aim of this study was to evaluate the rates of parasitaemia clearance and the prevalence of treatment failure in patients with uncomplicated Plasmodium falciparum malaria treated with artemether-lumefantrine (AL), mefloquine (MQ), and atovaquone-proguanil (AP). METHOD: The retrospective descriptive study included adult patients with uncomplicated P. falciparum malaria treated at the University Hospital Bulovka in Prague from 2006 to 2019. Parasitaemia clearance was estimated using a linear regression model. RESULTS: The study included 72 patients with a median age of 33 years (IQR 27-45) and a male to female ratio of 3.2:1. Thirty-six patients (50.0%) were treated with AL, 27 (37.5%) with MQ and 9 (12.5%) with AP. The proportion of VFR and migrants was 22.2% with no significant differences among the three groups. The median time to the parasitaemia clearance was two days (IQR 2-3) in patients treated with AL versus four days in the MQ (IQR 3-4) and AP (IQR 3-4) groups, p < 0.001. The clearance rate constant was 3.3/hour (IQR 2.5-4.0) for AL, 1.6/hour (IQR 1.3-1.9) for MQ, and 1.9/hour (IQR 1.3-2.4) for AP, p < 0.001. Malaria recrudescence occurred in 5/36 (13.9%) patients treated with AL and in no patients treated with MQ or AP. CONCLUSIONS: The findings demonstrate the superior efficacy of AL compared to other oral antimalarials in early malaria treatment. However, we observed a higher rate of late treatment failure in patients treated with AL than previously reported. This issue warrants further investigation of possible dose adjustments, extended regimens, or alternative artemisinin-based combinations.
- MeSH
- antimalarika * škodlivé účinky MeSH
- artemether terapeutické užití MeSH
- dospělí MeSH
- ethanolaminy terapeutické užití MeSH
- fixní kombinace léků MeSH
- kombinace léků artemether a lumefantrin terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- malárie * farmakoterapie MeSH
- meflochin terapeutické užití škodlivé účinky MeSH
- neúspěšná terapie MeSH
- Plasmodium falciparum MeSH
- retrospektivní studie MeSH
- tropická malárie * farmakoterapie epidemiologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
T-2 toxin is a worldwide problem for feed and food safety, leading to livestock and human health risks. The objective of this study was to explore the mechanism of T-2 toxin-induced small intestine injury in broilers by integrating the advanced microbiomic, metabolomic and transcriptomic technologies. Four groups of 1-day-old male broilers (n = 4 cages/group, 6 birds/cage) were fed a control diet and control diet supplemented with T-2 toxin at 1.0, 3.0, and 6.0 mg/kg, respectively, for 2 weeks. Compared with the control, dietary T-2 toxin reduced feed intake, body weight gain, feed conversion ratio, and the apparent metabolic rates and induced histopathological lesions in the small intestine to varying degrees by different doses. Furthermore, the T-2 toxin decreased the activities of glutathione peroxidase, thioredoxin reductase and total antioxidant capacity but increased the concentrations of protein carbonyl and malondialdehyde in the duodenum in a dose-dependent manner. Moreover, the integrated microbiomic, metabolomic and transcriptomic analysis results revealed that the microbes, metabolites, and transcripts were primarily involved in the regulation of nucleotide and glycerophospholipid metabolism, redox homeostasis, inflammation, and apoptosis were related to the T-2 toxin-induced intestinal damage. In summary, the present study systematically elucidated the intestinal toxic mechanisms of T-2 toxin, which provides novel ideas to develop a detoxification strategy for T-2 toxin in animals.
- MeSH
- antioxidancia metabolismus MeSH
- apoptóza MeSH
- dieta MeSH
- homeostáza MeSH
- krmivo pro zvířata analýza MeSH
- kur domácí * metabolismus MeSH
- lidé MeSH
- oxidace-redukce MeSH
- potravní doplňky MeSH
- T-2 toxin * toxicita MeSH
- zánět MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Bylo studováno antikonvulzivní spektrum původního slibného antikonvulziva N-[(2,4-dichlorfenyl) methyl]-2-(2,4-dioxo-1H-chinazolin-3-yl) acetamidu. Sloučenina vykazovala výrazný antikonvulzivní účinek a významně snižovala mortalitu myší na modelech záchvatů vyvolaných pentylenetetrazolem, pikrotoxinem, strychninem a kofeinem. Na modelu záchvatů vyvolaných thiosemikarbazidem testovaná sloučenina mortalitu nesnížila. Získané výsledky naznačily, že mechanismus antikonvulzivního účinku zahrnuje GABA-ergní (účinnost v modelech záchvatů vyvolaných pentylenetetrazolem a pikrotoxinem), glycinergní (účinnost v modelu paroxyzmů vyvolaných strychninem) a adenosynergní (účinnost v modelu záchvatů vyvolaných kofeinem). Molekulární dokování slibného antikonvulziva k antikonvulzivním biologickým cílům bylo v souladu s mechanismy chemoindukovaných záchvatů, konkrétně GABA, glycinu a adenosinových receptorů typu A2A, GABAAT a enzymů BCAT. Byla zjištěna shoda mezi výsledky studií in vivo a in silico.
The anticonvulsant spectrum of the original promising anticonvulsant N-[(2,4-dichlorophenyl) methyl]-2-(2,4-dioxo-1H-quinazolin-3-yl) acetamide was studied. The compound had a pronounced anticonvulsant effect, significantly reducing the mortality of mice in models of seizures induced by pentylenetetrazole, picrotoxin, strychnine, and caffeine. In the thiosemicarbazideinduced seizure model, the test compound did not reduce mortality. The obtained results indicated that the mechanism of anticonvulsant action involved GABA-ergic (effective in models of pentylenetetrazole and picrotoxin-induced seizures), glycinergic (efficiency in the strychnine model of paroxysms), and adenosinergic (effectiveness in the model of caffeine induced seizures). Molecular docking of a promising anticonvulsant to anticonvulsant biotargets follow the mechanisms of chemo-induced seizures, namely GABA, glycine, and adenosine receptors type A2A, GABAAT, and BCAT enzymes. The conformity between in vivo and in silico studies results was revealed.
- MeSH
- acetamidy farmakologie MeSH
- akční spektrum MeSH
- antikonvulziva * farmakologie MeSH
- kofein MeSH
- modely nemocí na zvířatech MeSH
- pentylentetrazol MeSH
- pikrotoxin MeSH
- receptory GABA MeSH
- simulace molekulového dockingu MeSH
- záchvaty chemicky indukované farmakoterapie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
