In this work, we report the application of Buchwald-Hartwig amination for the preparation of new derivatives of quercetin and luteolin. Our investigation delves into the impact of aniline moiety on antioxidant, and anti-inflammatory activity, cytotoxicity, and the ability of flavonoids to modulate drug-resistance mechanisms in bacteria. The anti-inflammatory activity disappeared after the introduction of aniline into the flavonoids and the cytotoxicity remained low. Although the ability of quercetin and luteolin to modulate bacterial resistance to antibiotics has already been published, this is the first report on the molecular mechanism of this process. Both flavonoids attenuate erythromycin resistance by suppressing the ribosomal methyltransferase encoded by the ermA gene in Staphylococcus aureus. Notably, 4-(trifluoromethyl)anilino quercetin emerged as a potent ErmA inhibitor, likely by interacting with the RNA-binding pocket of ErmA. Additionally, both 4-fluoroanilino derivatives effectively impended the staphylococcal efflux system. All the prepared derivatives exhibited superior activity in modulating gentamicin resistance in S. aureus compared to the parent compounds. Overall, the incorporation of substituted anilines into the flavonoid core significantly enhanced its ability to combat multidrug resistance in bacteria.

• Publication type
• Journal Article MeSH

Lilial (also called lysmeral) is a fragrance ingredient presented in many everyday cosmetics and household products. The concentrations of lilial in the final products is rather low. Its maximum concentration in cosmetics was limited and recently, its use in cosmetics products was prohibited in the EU due to the classification as reproductive toxicant. Additionally, according to the European Chemicals Agency, it was under assessment as one of the potential endocrine disruptors, i.e. a substance that may alter the function of the endocrine system and, as a result, cause health problems. Its ability to act as an androgen receptor agonist and the estrogenic and androgenic activity of its metabolites, to the best of our knowledge, have not yet been tested. The aim of this work was to determine the intestinal absorption, cytotoxicity, nephrotoxicity, mutagenicity, activation of cellular stress-related signal pathways and, most importantly, to test the ability to disrupt the endocrine system of lilial and its Phase I metabolites. This was tested using set of in vitro assays including resazurin assay, the CHO/HPRT mutation assay, γH2AX biomarker-based genotoxicity assay, qPCR and in vitro reporter assays based on luminescence of luciferase for estrogen, androgen, NF-κB and NRF2 signalling pathway. It was determined that neither lilial nor its metabolites have a negative effect on cell viability in the concentration range from 1 nM to 100 µM. Using human cell lines HeLa9903 and MDA-kb2, it was verified that this substance did not have agonistic activity towards estrogen or androgen receptor, respectively. Lilial metabolites, generated by incubation with the rat liver S9 fraction, did not show the ability to bind to estrogen or androgen receptors. Neither lilial nor its metabolites showed a nephrotoxic effect on human renal tubular cells (RPTEC/TERT1 line) and at the same time they were unable to activate the NF-κB and NRF2 signalling pathway at a concentration of 50 µM (HEK 293/pGL4.32 or pGL4.37). Neither lilial nor its metabolites showed mutagenic activity in the HPRT gene mutation test in CHO-K1 cells, nor were they able to cause double-strand breaks in DNA (γH2AX biomarker) in CHO-K1 and HeLa cells. In our study, no negative effects of lilial or its in vitro metabolites were observed up to 100 µM using different in vitro tests.

• MeSH
• Androgens MeSH
• Biomarkers MeSH
• Estrogens toxicity   metabolism   MeSH
• NF-E2-Related Factor 2 MeSH
• HEK293 Cells MeSH
• HeLa Cells MeSH
• Hypoxanthine Phosphoribosyltransferase * MeSH
• Rats MeSH
• Humans MeSH
• NF-kappa B * MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Androgens MeSH
• Biomarkers MeSH
• Estrogens MeSH
• NF-E2-Related Factor 2 MeSH
• Hypoxanthine Phosphoribosyltransferase * MeSH
• lilial MeSH Browser
• NF-kappa B * MeSH

A library of previously unknown halogenated derivatives of flavonolignans (silybins A and B, 2,3-dehydrosilybin, silychristin A, and 2,3-dehydrosilychristin A) was prepared. The effect of halogenation on the biological activity of flavonolignans was investigated. Halogenated derivatives had a significant effect on bacteria. All prepared derivatives inhibited the AI-2 type of bacterial communication (quorum sensing) at concentrations below 10 µM. All prepared compounds also inhibited the adhesion of bacteria (Staphyloccocus aureus and Pseudomonas aeruginosa) to the surface, preventing biofilm formation. These two effects indicate that the halogenated derivatives are promising antibacterial agents. Moreover, these derivatives acted synergistically with antibiotics and reduced the viability of antibiotic-resistant S. aureus. Some flavonolignans were able to reverse the resistant phenotype to a sensitive one, implying that they modulate antibiotic resistance.

• Keywords
• bacteria, biological activity, flavonoids, flavonolignans, halogenation, multidrug resistance,
• MeSH
• Anti-Bacterial Agents pharmacology   MeSH
• Bacteria MeSH
• Biofilms MeSH
• Methicillin-Resistant Staphylococcus aureus * MeSH
• Pseudomonas aeruginosa MeSH
• Quorum Sensing MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anti-Bacterial Agents MeSH

In the food industry, the increasing antimicrobial resistance of food-borne pathogens to conventional sanitizers poses the risk of food contamination and a decrease in product quality and safety. Therefore, we explored alternative antimicrobials N-Acetyl-l-cysteine (NAC), rhamnolipids (RLs), and usnic acid (UA) as a novel approach to prevent biofilm formation and reduce existing biofilms formed by important food-borne pathogens (three strains of Salmonella enterica and two strains of Escherichia coli, Listeria monocytogenes, Staphylococcus aureus). Their effectiveness was evaluated by determining minimum inhibitory concentrations needed for inhibition of bacterial growth, biofilm formation, metabolic activity, and biofilm reduction. Transmission electron microscopy and confocal scanning laser microscopy followed by image analysis were used to visualize and quantify the impact of tested substances on both planktonic and biofilm-associated cells. The in vitro cytotoxicity of the substances was determined as a half-maximal inhibitory concentration in five different cell lines. The results indicate relatively low cytotoxic effects of NAC in comparison to RLs and UA. In addition, NAC inhibited bacterial growth for all strains, while RLs showed overall lower inhibition and UA inhibited only the growth of Gram-positive bacteria. Even though tested substances did not remove the biofilms, NAC represents a promising tool in biofilm prevention.

• Keywords
• N-Acetyl-l-cysteine, acute cytotoxicity, antimicrobial efficacy, bacterial growth, biofilm, food-borne pathogens, minimum inhibitory concentrations, rhamnolipids, usnic acid,
• MeSH
• Acetylcysteine pharmacology   MeSH
• Anti-Bacterial Agents pharmacology   MeSH
• Anti-Infective Agents pharmacology   MeSH
• Benzofurans pharmacology   MeSH
• Biofilms drug effects   MeSH
• Cell Line MeSH
• Escherichia coli drug effects   MeSH
• Glycolipids pharmacology   MeSH
• Food Contamination prevention & control   MeSH
• Humans MeSH
• Listeria monocytogenes drug effects   MeSH
• Microbial Sensitivity Tests MeSH
• Foodborne Diseases drug therapy   microbiology   MeSH
• Food Microbiology methods   MeSH
• Salmonella enterica drug effects   MeSH
• Staphylococcus aureus drug effects   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Acetylcysteine MeSH
• Anti-Bacterial Agents MeSH
• Anti-Infective Agents MeSH
• Benzofurans MeSH
• Glycolipids MeSH
• rhamnolipid MeSH Browser
• usnic acid MeSH Browser

Although some metallic nanoparticles (NPs) are commonly used in the food processing plants as nanomaterials for food packaging, or as coatings on the food handling equipment, little is known about antimicrobial properties of palladium (PdNPs) and platinum (PtNPs) nanoparticles and their potential use in the food industry. In this study, common food-borne pathogens Salmonella enterica Infantis, Escherichia coli, Listeria monocytogenes and Staphylococcus aureus were tested. Both NPs reduced viable cells with the log10 CFU reduction of 0.3-2.4 (PdNPs) and 0.8-2.0 (PtNPs), average inhibitory rates of 55.2-99% for PdNPs and of 83.8-99% for PtNPs. However, both NPs seemed to be less effective for biofilm formation and its reduction. The most effective concentrations were evaluated to be 22.25-44.5 mg/L for PdNPs and 50.5-101 mg/L for PtNPs. Furthermore, the interactions of tested NPs with bacterial cell were visualized by transmission electron microscopy (TEM). TEM visualization confirmed that NPs entered bacteria and caused direct damage of the cell walls, which resulted in bacterial disruption. The in vitro cytotoxicity of individual NPs was determined in primary human renal tubular epithelial cells (HRTECs), human keratinocytes (HaCat), human dermal fibroblasts (HDFs), human epithelial kidney cells (HEK 293), and primary human coronary artery endothelial cells (HCAECs). Due to their antimicrobial properties on bacterial cells and no acute cytotoxicity, both types of NPs could potentially fight food-borne pathogens.

• Keywords
• acute cytotoxicity, antimicrobial properties, food-borne pathogens, minimum inhibitory concentrations, palladium nanoparticles, platinum nanoparticles,
• MeSH
• Anti-Bacterial Agents chemistry   pharmacology   MeSH
• Bacteria classification   drug effects   growth & development   MeSH
• Fibroblasts cytology   drug effects   MeSH
• Metal Nanoparticles administration & dosage   chemistry   MeSH
• Cells, Cultured MeSH
• Kidney cytology   drug effects   MeSH
• Humans MeSH
• Foodborne Diseases prevention & control   MeSH
• Palladium chemistry   MeSH
• Platinum chemistry   MeSH
• Food Microbiology MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anti-Bacterial Agents MeSH
• Palladium MeSH
• Platinum MeSH

Mycotoxins are secondary metabolites produced by several species of fungi, including the Fusarium, Aspergillus, and Penicillium species. Currently, more than 300 structurally diverse mycotoxins are known, including a group called minor mycotoxins, namely enniatins, beauvericin, and fusaproliferin. Beauvericin and enniatins possess a variety of biological activities. Their antimicrobial, antibiotic, or ionoforic activities have been proven and according to various bioassays, they are believed to be toxic. They are mainly found in cereal grains and their products, but they have also been detected in forage feedstuff. Mycotoxins in feedstuffs of livestock animals are of dual concern. First one relates to the safety of animal-derived food. Based on the available data, the carry-over of minor mycotoxins from feed to edible animal tissues is possible. The second concern relates to detrimental effects of mycotoxins on animal health and performance. This review aims to summarize current knowledge on the relation of minor mycotoxins to livestock animals.

• Keywords
• beauvericin, carry-over, enniatins, feed, metabolism, minor mycotoxins,
• MeSH
• Depsipeptides toxicity   MeSH
• Livestock MeSH
• Edible Grain toxicity   MeSH
• Food Contamination analysis   MeSH
• Animal Feed toxicity   MeSH
• Mycotoxins * MeSH
• Terpenes MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• beauvericin MeSH Browser
• Depsipeptides MeSH
• enniatins MeSH Browser
• fusaproliferin MeSH Browser
• Mycotoxins * MeSH
• Terpenes MeSH

Selaginella P. Beauv. is a group of vascular plants in the family Selaginellaceae Willk., found worldwide and numbering more than 700 species, with some used as foods and medicines. The aim of this paper was to compare methanolic (MeOH) and dichloromethane (DCM) extracts of eight Selaginella species on the basis of their composition and biological activities. Six of these Selaginella species are underinvestigated. Using ultra-high performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) analysis, we identified a total of 193 compounds among the tested Selaginella species, with flavonoids predominating. MeOH extracts recovered more constituents that were detected, including selaginellins, the occurrence of which is only typical for this plant genus. Of all the tested species, Selaginella apoda contained the highest number of identified selaginellins. The majority of the compounds were identified in S. apoda, the fewest compounds in Selaginella cupressina. All the tested species demonstrated antioxidant activity using oxygen radical absorption capacity (ORAC) assay, which showed that MeOH extracts had higher antioxidant capacity, with the half maximal effective concentration (EC50) ranging from 12 ± 1 (Selaginella myosuroides) to 124 ± 2 (Selaginella cupressina) mg/L. The antioxidant capacity was presumed to be correlated with the content of flavonoids, (neo)lignans, and selaginellins. Inhibition of acetylcholinesterase (AChE) was mostly discerned in DCM extracts and was only exhibited in S. myosuroides, S. cupressina, Selaginella biformis, and S. apoda extracts with the half maximal inhibitory concentration (IC50) in the range of 19 ± 3 to 62 ± 1 mg/L. Substantial cytotoxicity against cancer cell lines was demonstrated by the MeOH extract of S. apoda, where the ratio of the IC50 HEK (human embryonic kidney) to IC50 HepG2 (hepatocellular carcinoma) was 7.9 ± 0.2. MeOH extracts inhibited the production of nitrate oxide and cytokines in a dose-dependent manner. Notably, S. biformis halved the production of NO, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 at the following concentrations: 105 ± 9, 11 ± 1, and 10 ± 1 mg/L, respectively. Our data confirmed that extracts from Selaginella species exhibited cytotoxicity against cancer cell lines and AChE inhibition. The activity observed in S. apoda was the most promising and is worth further exploration.

• Keywords
• AChE inhibition, Selaginella, anti-inflammatory, cytotoxicity, flavonoids, selaginellins,
• Publication type
• Journal Article MeSH

The determination of mycotoxins content in food is not sufficient for the prediction of their potential in vivo cytotoxicity because it does not reflect their bioavailability and mutual interactions within complex matrices, which may significantly alter the toxic effects. Moreover, many mycotoxins undergo biotransformation and metabolization during the intestinal absorption process. Biotransformation is predominantly the conversion of mycotoxins meditated by cytochrome P450 and other enzymes. This should transform the toxins to nontoxic metabolites but it may possibly result in unexpectedly high toxicity. Therefore, the verification of biotransformation and bioavailability provides valuable information to correctly interpret occurrence data and biomonitoring results. Among all of the methods available, the in vitro models using monolayer formed by epithelial cells from the human colon (Caco-2 cell) have been extensively used for evaluating the permeability, bioavailability, intestinal transport, and metabolism of toxic and biologically active compounds. Here, the strengths and limitations of both in vivo and in vitro techniques used to determine bioavailability are reviewed, along with current detailed data about biotransformation of mycotoxins. Furthermore, the molecular mechanism of mycotoxin effects is also discussed regarding the disorder of intestinal barrier integrity induced by mycotoxins.

• Keywords
• bioavailability, biotransformation, cytochrome, intestinal transport, metabolism, mycotoxins, permeability,
• MeSH
• Biological Availability MeSH
• Caco-2 Cells MeSH
• Epithelial Cells enzymology   MeSH
• Risk Assessment MeSH
• Intestinal Absorption * MeSH
• Humans MeSH
• Activation, Metabolic MeSH
• Inactivation, Metabolic MeSH
• Mycotoxins metabolism   toxicity   MeSH
• Permeability MeSH
• Intestinal Mucosa enzymology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Mycotoxins MeSH

The inhibition and eradication of oral biofilms is increasingly focused on the use of plant extracts as mouthwashes and toothpastes adjuvants. Here, we report on the chemical composition and the antibiofilm activity of 15 methanolic extracts of Iris species against both mono-(Pseudomonas aeruginosa, Staphylococcus aureus) and multi-species oral biofilms (Streptococcus gordonii, Veillonella parvula, Fusobacterium nucleatum subsp. nucleatum, and Actinomyces naeslundii). The phytochemical profiles of Iris pallida s.l., Iris versicolor L., Iris lactea Pall., Iris carthaliniae Fomin, and Iris germanica were determined by ultra-high performance liquid chromatography-high-resolution tandem mass spectroscopy (UHPLC-HRMS/MS) analysis, and a total of 180 compounds were identified among Iris species with (iso)flavonoid dominancy. I. pallida, I. versicolor, and I. germanica inhibited both the quorum sensing and adhesion during biofilm formation in a concentration-dependent manner. However, the extracts were less active against maturated biofilms. Of the five tested species, Iris pallida s.l. was the most effective at both inhibiting biofilm formation and disrupting existing biofilms, and the leaf extract exhibited the strongest inhibitory effect compared to the root and rhizome extracts. The cytotoxicity of the extracts was excluded in human fibroblasts. The inhibition of bacterial adhesion significantly correlated with myristic acid content, and quorum sensing inhibition correlated with the 7-β-hydroxystigmast-4-en-3-one content. These findings could be useful for establishing an effective tool for the control of oral biofilms and thus dental diseases.

• Keywords
• biofilm, dental plaque, microbial resistance, quorum sensing,
• Publication type
• Journal Article MeSH

Knotweed is a flowering plant that is native to temperate and subtropical regions in the northern hemisphere. We evaluated Japanese (Reynoutria japonica Houtt.) and Bohemian (Fallopia x bohemica) knotweed rhizome and flower ethanol extracts and compared them in terms of their biological activities. The specific polyphenols were identified and quantified using HPLC/DAD, and the antioxidant activity was determined using 2,2-diphenly-1-picrylhydrazyl (DPPH) and cellular antioxidant capacity assays. The anticancer activity was evaluated as the difference between the cytotoxicity to cancer cells compared with control cells. The antimicrobial activity was determined using bacteria and yeast. The antidiabetic activity was tested as the ability of the extracts to inhibit α-amylase. Both rhizome extracts were sources of polyphenols, particularly polydatin and (-)-epicatechin; however, the cellular assay showed the highest antioxidant capacity in the flower extract of F. bohemica. The PaTu cell line was the least sensitive toward all knotweed extracts. The flower extracts of both species were less toxic than the rhizomes. However, the activity of the tested extracts was not specific for cancer cells, indicating a rather toxic mode of action. Furthermore, all used extracts decreased the α-amylase activity, and the rhizome extracts were more effective than the flower extracts. None of the extracts inhibited bacterial growth; however, they inhibited yeast growth. The results confirmed that rhizomes of Reynoutria japonica Houtt. could become a new source of bioactive compounds, which could be used for the co-treatment of diabetes and as antifungal agents.

• Keywords
• anticancer activity, antidiabetic activity, antimicrobial activity, antioxidant activity, cellular antioxidant activity, herbal medicine, polyphenols,
• Publication type
• Journal Article MeSH