Honey can benefit from non-thermal processing techniques such as high-pressure processing (HPP) to improve its quality and bioactivity. This study investigated the impact of HPP (600 MPa for 5, 10, and 15 min) on honey's quality, including the levels of hydroxymethylfurfural (HMF), antioxidant activity, total phenolic content (TPC), and phenolic profile. HPP treatment did not significantly affect HMF or TPC levels but led to selective changes in the phenolic profile. Despite a reduction in certain phenolic compound content, HPP for 5 and 15 min caused a significant increase in the antioxidant activity (2,2-diphenyl-1-picrylhydrazyl [DPPH]) of honey from the mean value of 41.8% to values of 45.4% and 49.6%, respectively. On the other hand, HPP for 10 min did not change the antioxidant activity of tested honey. A 27.5% reduction in the equatorial diameter of pollen grains was observed after HPP combined with temperature at 75°C, suggesting an improved release of bioactive compounds. The content of specific phenolic compounds, including caffeic acid, p-coumaric acid, sinapic acid, naringin, kaempferol, and the TPC, significantly affected the DPPH activity. The increment in the antioxidant activity of HPP honey may be attributed to selective changes in the content of certain phenolic compounds and improved their extraction from pollen grains.

• Klíčová slova
• antioxidant activity, high‐pressure processing, honey, polyphenols, quality,
• MeSH
• 2-furaldehyd analogy a deriváty   analýza   MeSH
• antioxidancia * chemie   farmakologie   analýza   MeSH
• bifenylové sloučeniny antagonisté a inhibitory   MeSH
• fenoly * analýza   chemie   farmakologie   MeSH
• med * analýza   MeSH
• pikráty antagonisté a inhibitory   MeSH
• pyl * chemie   MeSH
• tlak * MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 1,1-diphenyl-2-picrylhydrazyl MeSH Prohlížeč
• 2-furaldehyd MeSH
• 5-hydroxymethylfurfural MeSH Prohlížeč
• antioxidancia * MeSH
• bifenylové sloučeniny MeSH
• fenoly * MeSH
• pikráty MeSH

Endoplasmic reticulum (ER) and lysosomes are physiologically active, physically and functionally connected intracellular Ca2+ stores. In this study we investigated agonist-triggered Ca2+ release from these two stores in mouse microvascular endothelial bEND.3 cells. Addition of nigericin to discharge lysosomal Ca2+ did not affect endoplasmic reticulum Ca2+ release induced by cyclopiazonic acid (CPA) and vice versa, suggesting lysosomes and ER were separate Ca2+ stores whose Ca2+ content was not readily reduced by depletion of the counterpart. ATP triggered Ca2+ release was partially inhibited by Ned-19 (lysosomal two-pore channel inhibitor) or xestospongin C (inositol 1,4,5-trisphosphate receptor-channel inhibitor), suggesting ATP mobilized Ca2+ from both ER and lysosomes. Whilst ATP-triggered Ca2+ release did not affect subsequent CPA- or nigericin-induced Ca2+ discharge, pretreatment with either CPA or nigericin abolished subsequent ATP-triggered Ca2+ release. Thus, the empty state of ER suppressed lysosomal Ca2+ release elicited by ATP, and vice versa, the empty state of lysosome inhibited ATP triggered Ca2+ release from ER. These data suggest cross-talk of the two organelles on the Ca2+ filling state to regulate agonist-stimulated Ca2+ release of each other.

• MeSH
• adenosintrifosfát metabolismus   farmakologie   MeSH
• buněčné linie MeSH
• endoplazmatické retikulum * metabolismus   účinky léků   MeSH
• endoteliální buňky * metabolismus   účinky léků   MeSH
• indoly farmakologie   MeSH
• lyzozomy * metabolismus   účinky léků   MeSH
• myši MeSH
• nigericin farmakologie   MeSH
• vápník * metabolismus   MeSH
• vápníková signalizace * účinky léků   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adenosintrifosfát MeSH
• cyclopiazonic acid MeSH Prohlížeč
• indoly MeSH
• nigericin MeSH
• vápník * MeSH

The literature documenting the value of drug-like molecules found in natural products is vast. Although many dietary and herbal remedies have been found to be effective for treating intestinal inflammation, the identification of their active components has lagged behind. In this study, we find that a major ginger component, furanodienone (FDN), is a selective pregnane X receptor (PXR) ligand with agonistic transcriptional outcomes. We show that FDN binds within a sub-pocket of the PXR ligand binding domain (LBD), with subsequent alterations in LBD structure. Using male mice, we show that orally provided FDN has potent PXR-dependant anti-inflammatory outcomes that are colon-specific. Increased affinity and target gene activation in the presence of synergistically acting agonists indicates further opportunities for augmenting FDN activity, efficacy and safety. Collectively, these results support the translational potential of FDN as a therapeutic agent for the treatment and prevention of colonic diseases.

• MeSH
• antiflogistika * farmakologie   MeSH
• furany * farmakologie   chemie   MeSH
• kolitida * farmakoterapie   MeSH
• kolon účinky léků   patologie   MeSH
• lidé MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• pregnanový X receptor * metabolismus   genetika   MeSH
• zánět farmakoterapie   MeSH
• zázvor lékařský * chemie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antiflogistika * MeSH
• furany * MeSH
• pregnanový X receptor * MeSH

The RNA binding protein Human Antigen R (HuR) has been identified as a main regulator of the innate immune response and its inhibition can lead to beneficial anti-inflammatory effects. To this aim, we previously synthesized a novel class of small molecules named Tanshinone Mimics (TMs) able to interfere with HuR-RNA binding, and that dampen the LPS-induced immune response. Herein, we present a novel series of TMs, encompassing thiophene 3/TM9 and 4/TM10, furan 5/TM11 and 6/TM12, pyrrole 7b/TM13, and pyrazole 8. The furan-containing 5(TM11) showed the greatest inhibitory effect of the series on HuR-RNA complex formation, as suggested by RNA Electromobility Shift Assay and Time-Resolved FRET. Molecular Dynamics Calculation of HuR - 5/TM11 interaction, quantum mechanics approaches and Surface Plasmon Resonance data, all indicates that, within the novel heteroaryl substituents, the furan ring better recapitulates the chemical features of the RNA bound to HuR. Compound 5/TM11 also showed improved aqueous solubility compared to previously reported TMs. Real-time monitoring of cell growth and flow cytometry analyses showed that 5/TM11 preferentially reduced cell proliferation rather than apoptosis in murine macrophages at immunomodulatory doses. We observed its effects on the innate immune response triggered by lipopolysaccharide (LPS) in macrophages, showing that 5/TM11 significantly reduced the expression of proinflammatory cytokines as Cxcl10 and Il1b.

• Klíčová slova
• Anti-inflammatory agents, ELAVL1, HuR, HuR inhibitors, LPS, Tanshinone mimics,
• MeSH
• antiflogistika farmakologie   chemie   MeSH
• apoptóza účinky léků   MeSH
• chemokin CXCL10 metabolismus   MeSH
• diterpeny abietanové * farmakologie   chemie   MeSH
• furany farmakologie   chemie   MeSH
• HuR protein metabolismus   MeSH
• lidé MeSH
• lipopolysacharidy farmakologie   MeSH
• makrofágy * účinky léků   metabolismus   MeSH
• myši MeSH
• RAW 264.7 buňky MeSH
• rozpustnost MeSH
• simulace molekulární dynamiky MeSH
• zánět farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antiflogistika MeSH
• chemokin CXCL10 MeSH
• diterpeny abietanové * MeSH
• furany MeSH
• HuR protein MeSH
• lipopolysacharidy MeSH
• tanshinone MeSH Prohlížeč

Trilobolide and its analogues belong to the guaianolide type of sesquiterpene lactones, which are characteristic and widely distributed within the families Asteraceae and Apiaceae. Certain guaianolides are receiving continuously increasing attention for their promising sarco-endoplasmic reticulum Ca2+-ATPase (SERCA)-inhibitory activity. However, because of their alkylation capabilities, they are generally toxic. Therefore, the search for compounds with significant immunobiological properties but with decreased cytotoxicities suitable for use in immune-based pharmacotherapy is ongoing. Therefore, we extended our previous investigation of the immunobiological effects of trilobolide to a series of structurally related guaianolides and germacranolides. To evaluate the relationship, we tested a series of selected derivatives containing α-methyl lactone or exomethylene lactone ring. For a wider comparison, we also included some of their glycosidic derivatives. We assessed the in vitro immunobiological effects of the tested compounds on nitric oxide (NO) production, cytokine secretion, and prostaglandin E2 (PGE2) release by mouse peritoneal cells, activated primarily by lipopolysaccharide (LPS), and evaluated their viability. The inhibitory effects of the apparently most active substance, 8-deoxylactucin, seem to be the most promising.

• Klíčová slova
• 8-deoxylactucin, 8-epiisoamberboin, germacranolides, guaianolides, immune-modulatory effects,
• MeSH
• butyráty MeSH
• cytokiny metabolismus   MeSH
• dinoproston metabolismus   biosyntéza   MeSH
• furany MeSH
• laktony * farmakologie   chemie   MeSH
• lipopolysacharidy farmakologie   MeSH
• myši MeSH
• oxid dusnatý * metabolismus   MeSH
• peritoneální makrofágy účinky léků   metabolismus   MeSH
• seskviterpeny germakranové * farmakologie   chemie   MeSH
• seskviterpeny guajanové * farmakologie   chemie   MeSH
• seskviterpeny farmakologie   chemie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• butyráty MeSH
• cytokiny MeSH
• dinoproston MeSH
• furany MeSH
• germacranolide MeSH Prohlížeč
• laktony * MeSH
• lipopolysacharidy MeSH
• oxid dusnatý * MeSH
• seskviterpeny germakranové * MeSH
• seskviterpeny guajanové * MeSH
• seskviterpeny MeSH
• trilobolide MeSH Prohlížeč

Metabolites of the edible and medicinal plant Arctium have been shown to possess beneficial activities. The phytochemical profile of Arctium lappa is well-explored and its fruits are known to contain mainly lignans, fatty acids, and sterols. But the fruits of other Arctium species have not been thoroughly investigated. Therefore, this study compares the metabolic profiles of the fruits of A. lappa, Arctium tomentosum, and Arctium minus. Targeted metabolomics led to the putative identification of 53 metabolites in the fruit extracts, the majority of these being lignans and fatty acids. Quantification of the major lignans showed that the year of collection had a significant effect on the lignan content. Furthermore, A. lappa fruits contained lesser amounts of arctigenin but greater amounts of arctigenin glycoside than A. minus fruits. Regarding the profile of fatty acids, A. minus fruits differed from the others in the presence of linolelaidic acid.

• Klíčová slova
• Arctium, burdock, Fatty acids, LC-MS, Lignans, Metabolomics,
• MeSH
• Arctium * chemie   MeSH
• furany analýza   metabolismus   MeSH
• fytonutrienty analýza   MeSH
• lignany * analýza   MeSH
• mastné kyseliny * analýza   metabolismus   MeSH
• metabolom MeSH
• metabolomika MeSH
• ovoce * chemie   MeSH
• rostlinné extrakty * analýza   chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• arctigenin MeSH Prohlížeč
• furany MeSH
• fytonutrienty MeSH
• lignany * MeSH
• mastné kyseliny * MeSH
• rostlinné extrakty * MeSH

Two silver(I) complexes with biologically relevant heterocyclic ligands, pyrrole and furan-2- carboxylic acid, were synthesized and their composition was confirmed using elemental, spectral, thermal and structural analyses. The {[Ag(Py2c)]}n (AgPy2c, Py2c = pyrrole-2-carboxylate) and {[Ag(Fu2c)]}n (AgFu2c, Fu2c = furan-2-carboxylate) solubility and stability in biological test stock solution were confirmed by 1H NMR spectroscopy. The X-ray analysis has enabled us to determine typical argentophilic interactions and bridging carboxylate coordination mode of both ligands. Potentiometric data analysis by BSTAC program resulted in the determination of the stability constant of only one species, i.e., the ML (M = Ag+, L = Fu2c-), log βML = 0.59 ± 0.04. Antimicrobial and anticancer tests were performed against selected microorganisms and cell lines with new silver(I) complexes and compared with AgSD (silver(I) sulfadiazine) and cisplatin. From their microbial toxicity point of view, selectivity was determined against lactobacilli (AgPy2c is 8× more effective against S. aureus and E. coli and AgFu2c is 8× more effective against E. coli and 4× against S. aureus). AgFu2c significant anticancer activity was determined against Jurkat cell lines (IC50 = 8.00 μM) and was similar to cisPt (IC50 = 6.3 μM) similarly to its selectivity (SI (AgFu2c) = 7.3, SI (cisPt) = 6.4, SI = selectivity index). In addition, cell cycle arrest was observed already in the Sub-G0 phase during a flow cytometry experiment. To evaluate the AgPy2c and AgFu2c bioavailability we also discuss their Lipinski's Rule of Five.

• Klíčová slova
• Anticancer, Antimicrobial, Cell cycle, Crystallography, Lipophilicity, Potentiometry, Selectivity, Silver(I) complexes, Stability,
• MeSH
• antibakteriální látky farmakologie   chemie   MeSH
• antiinfekční látky * farmakologie   chemie   MeSH
• Escherichia coli MeSH
• furany farmakologie   MeSH
• komplexní sloučeniny * farmakologie   chemie   MeSH
• ligandy MeSH
• mikrobiální testy citlivosti MeSH
• Staphylococcus aureus MeSH
• stříbro farmakologie   chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 2-furoic acid MeSH Prohlížeč
• antibakteriální látky MeSH
• antiinfekční látky * MeSH
• furany MeSH
• komplexní sloučeniny * MeSH
• ligandy MeSH
• stříbro MeSH

Quorum Sensing allows bacteria to sense their population density via diffusible N-acyl homoserine lactone (N-HL) signaling molecules. Upon reaching a high enough cell density, bacteria will collectively exhibit a phenotype. Until recently, methods used for detection of N-HLs have not considered the chirality of these molecules and it was assumed that only the L-enantiomer was produced by bacteria. The production and effects of D-N-HLs have rarely been studied. In this work, the temporal production of D-N-HLs by the plant pathogen Pectobacterium atrosepticum and the human pathogen Pseudomonas aeruginosa are reported. Both bacteria produced D-N-HLs in significant amounts and in some cases their concentrations were higher than other low abundance L-N-HLs. Previously unreported D-enantiomers of N-3-oxoacyl and N-3-hydroxyacyl homoserine lactones were detected in P. atrosepticum. Interestingly, L-N-HLs produced in the lowest concentrations had relatively higher amounts of their corresponding D-enantiomers. Potential sources of D-N-HLs and their significance are considered.

• MeSH
• acylbutyrolaktony * farmakologie   MeSH
• Bacteria MeSH
• gama-butyrolakton MeSH
• homoserin farmakologie   MeSH
• laktony MeSH
• lidé MeSH
• Pectobacterium * MeSH
• Pseudomonas aeruginosa MeSH
• quorum sensing genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• acylbutyrolaktony * MeSH
• gama-butyrolakton MeSH
• homoserin MeSH
• laktony MeSH

In the present study, we investigated the effect of acrylamide (ACR) exposure during pregnancy on the ovary of female adult offspring of two subsequent generations. Sixty-day-old Wistar albino female rats were given different doses of ACR (2.5 and 10 mg/kg/day) from day 6 of pregnancy until giving birth. Females from the first generation (AF1) were fed ad libitum, and thereafter, a subgroup was euthanized at 8 weeks of age and ovary samples were obtained. The remaining females were maintained until they reached sexual maturity (50 days old) and then treated in the same way as the previous generation to obtain the second generation of females (AF2). The histopathological examination indicated a high frequency of corpora lutea along with an increased number of antral follicles that reached the selectable stage mainly at a dose of 2.5 mg/kg/day. Interestingly, ACR exposure significantly increased the mRNA levels of CYP19 gene and its corresponding CYP19 protein expression in AF1 females. The TUNEL assay showed a significantly high rate of apoptosis in stromal cells except for dose of 2.5 mg/kg/day. However, in AF2 females, ACR exposure significantly increased the number of degenerating follicles and cysts while the number of growing follicles was reduced. Moreover, in both ACR-treated groups, estradiol-producing enzyme CYP19A gene and its corresponding protein were significantly reduced, and an excessive apoptosis was produced. We concluded that the ovarian condition of AF1 females had considerable similarity to the typical early perimenopausal stage, whereas that of AF2 females was similar to the late perimenopausal stage in women.

• MeSH
• akrylamid toxicita   MeSH
• apoptóza MeSH
• aromatasa * genetika   MeSH
• furylfuramid MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• poměr pohlaví MeSH
• potkani Wistar MeSH
• těhotenství MeSH
• zpožděný efekt prenatální expozice * chemicky indukované   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• akrylamid MeSH
• aromatasa * MeSH
• furylfuramid MeSH

N-acyl homoserine lactones (N-HLs) are signaling molecules used by Gram-negative bacteria in a phenomenon called quorum sensing. Bacteria will detect N-HLs as a way of monitoring their population which, upon reaching a critical level, will express a specific phenotype. An example is the expression of bioluminescence by Vibrio fischeri. Most studies have not considered the chirality of these molecules nor have they used highly sensitive detection methods. Here, the production of d,l-N-HLs are monitored for V. fischeri, Burkholderia cepacia, Pseudomonas fluorescens, and P. putida, using highly sensitive tandem mass spectrometry analysis. Novel N-HLs are reported for both V. fischeri and B. cepacia, including a plethora of previously unknown d-N-HLs, including the first d-N-HLs containing oxo and hydroxy functionalities. Anomalously, N-HLs were not detected in any cultures of P. fluorescens and P. putida, which are species that previously were reported to produce N-HLs. However, it is apparent that differences in the reported occurrence and levels of N-HLs can result from (a) different strains of bacteria, (b) different growth media and environmental conditions, and (c) sometimes false-positive results from detection methodologies. Time studies of V. fischeri suggest the possibility that separate synthetic and elimination pathways exist between d- and l-N-HLs. Possible biological processes that could be the source of d-N-HL production are considered.

• Klíčová slova
• bioluminescence, chemical communication, chirality, homoserine lactones, phenotype expression,
• MeSH
• Aliivibrio fischeri * chemie   metabolismus   MeSH
• Burkholderia cepacia * metabolismus   MeSH
• chromatografie kapalinová MeSH
• gama-butyrolakton metabolismus   MeSH
• plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
• quorum sensing MeSH
• tandemová hmotnostní spektrometrie MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• gama-butyrolakton MeSH