Antioxidants in nutrition are a widely discussed topic. In this study, a synergistic effect was observed for 13 selected substances - antioxidants and potential synergists, whereby two substances were mixed in the same concentration ratio of 1:1. The antioxidant capacity (AC) of the mixtures was determined using the FRAP method. The AC measured was compared with a theoretical AC value (as only additive effect) to calculate the synergistic or antagonistic effect. Out of 78 possible combinations, a synergistic effect (SE) was detected in 72. For the 10 combinations, the SE was more than twice that of the pure substances. The largest synergistic effect was exhibited by vanillin and 4-hydroxybenzoic acid with increases even above 200% compared to the pure substances. Some of the phenolic substances that were subject to measurement can be used for the fortification of fruit juices.

• Klíčová slova
• Antioxidants, Carboxylic acids, FRAP (ferric reducing antioxidant power), Methoxyphenols, Polyphenols, Synergistic effect,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Quercetin is a natural flavonoid, which widely exists in nature, such as tea, coffee, apples, and onions. Numerous studies have showed that quercetin has multiple biological activities such as anti-oxidation, anti-inflammatory, and anti-aging. Hence, quercetin has a significant therapeutic effect on cancers, obesity, diabetes, and other diseases. In the past decades, a large number of studies have shown that quercetin combined with other agents can significantly improve the overall therapeutic effect, compared to single use. PURPOSE: This work reviews the pharmacological activities of quercetin and its derivatives. In addition, this work also summarizes both in vivo and in vitro experimental evidence for the synergistic effect of quercetin against cancers and metabolic diseases. METHODS: An extensive systematic search for pharmacological activities and synergistic effect of quercetin was performed considering all the relevant literatures published until August 2021 through the databases including NCBI PubMed, Scopus, Web of Science, and Google Scholar. The relevant literatures were extracted from the databases with following keyword combinations: "pharmacological activities" OR "biological activities" OR "synergistic effect" OR "combined" OR "combination" AND "quercetin" as well as free-text words. RESULTS: Quercetin and its derivatives possess multiple pharmacological activities including anti-cancer, anti-oxidant, anti-inflammatory, anti-cardiovascular, anti-aging, and neuroprotective activities. In addition, the synergistic effect of quercetin with small molecule agents against cancers and metabolic diseases has also been confirmed. CONCLUSION: Quercetin cooperates with agents to improve the therapeutic effect by regulating signal molecules and blocking cell cycle. Synergistic therapy can reduce the dose of agents and avoid the possible toxic and side effects in the treatment process. Although quercetin treatment has some potential side effects, it is safe under the expected use conditions. Hence, quercetin has application value and potential strength as a clinical drug. Furthermore, quercetin, as the main effective therapeutic ingredient in traditional Chinese medicine, may effectively treat and prevent coronavirus disease 2019 (COVID-19).

• Klíčová slova
• Combination therapy, Pharmacological activities, Quercetin, Synergistic effect,
• MeSH
• antioxidancia farmakologie   MeSH
• COVID-19 * MeSH
• lidé MeSH
• quercetin * farmakologie   MeSH
• rostlinné extrakty MeSH
• SARS-CoV-2 MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antioxidancia MeSH
• quercetin * MeSH
• rostlinné extrakty MeSH

Antimicrobial materials are widely used for inhibition of microorganisms in the environment. It has been established that bacterial growth can be restrained by silver nanoparticles. Combining these with other antimicrobial agents, such as ZnO, may increase the antimicrobial activity and the use of carrier substrate makes the material easier to handle. In the paper, we present an antimicrobial nanocomposite based on silver nanoparticles nucleated in general silicate nanostructure ZnO·mSiO2. First, we prepared the silicate fine net nanostructure ZnO·mSiO2 with zinc content up to 30 wt% by precipitation of sodium water glass in zinc acetate solution. Silver nanoparticles were then formed within the material by photoreduction of AgNO3 on photoactive ZnO. This resulted into an Ag-ZnO·mSiO2 composite with silica gel-like morphology and the specific surface area of 250 m2/g. The composite, alongside with pure AgNO3 and clear ZnO·mSiO2, were successfully tested for antimicrobial activity on both gram-positive and gram-negative bacterial strains and yeast Candida albicans. With respect to the silver content, the minimal inhibition concentration of Ag-ZnO·mSiO2 was worse than AgNO3 only for gram-negative strains. Moreover, we found a positive synergistic antimicrobial effect between Ag and Zn agents. These properties create an efficient and easily applicable antimicrobial material in the form of powder.

• Klíčová slova
• antimicrobial effect, silver, synergistic effect, zinc oxide,
• Publikační typ
• časopisecké články MeSH

Diarrhoea remains an important public health concern, particularly in developing countries, and has become difficult to treat because of antibacterial resistance. The development of synergistic antimicrobial agents appears to be a promising alternative treatment against diarrhoeic infections. In this study, the combined effect of tetracycline together with either nitroxoline, sanguinarine, or zinc pyrithione (representing various classes of plant-based compounds) was evaluated in vitro against selected diarrhoeic bacteria (Enterococcus faecalis, Escherichia coli, Listeria monocytogenes, Shigella flexneri, Vibrio parahaemolyticus, and Yersinia enterocolitica). The chequerboard method in 96-well microtiter plates was used to determine the sum of the fractional inhibitory concentration indices (FICIs). Three independent experiments were performed per combination, each in triplicate. It was observed that the combination of tetracycline with either nitroxoline, sanguinarine, or zinc pyrithione produced synergistic effects against most of the pathogenic bacteria tested, with FICI values ranging from 0.086 to 0.5. Tetracycline-nitroxoline combinations produced the greatest synergistic action against S. flexneri at a FICI value of 0.086. The combinations of the agents tested in this study can thus be used for the development of new anti-diarrhoeic medications. However, studies focusing on their in vivo anti-diarrhoeic activity and safety are required before any consideration for utilization in human medicine.

• Klíčová slova
• antibacterial resistance, antimicrobial agents, combination therapy, diarrhoea, pathogens, synergistic effect,
• MeSH
• alkaloidy farmakologie   MeSH
• antibakteriální látky * farmakologie   MeSH
• Bacteria účinky léků   MeSH
• lidé MeSH
• mikrobiální testy citlivosti * MeSH
• nitrochinoliny farmakologie   MeSH
• organokovové sloučeniny MeSH
• průjem mikrobiologie   farmakoterapie   MeSH
• pyridiny farmakologie   MeSH
• synergismus léků * MeSH
• tetracyklin * farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alkaloidy MeSH
• antibakteriální látky * MeSH
• nitrochinoliny MeSH
• nitroxoline MeSH Prohlížeč
• organokovové sloučeniny MeSH
• pyridiny MeSH
• pyrithione zinc MeSH Prohlížeč
• tetracyklin * MeSH

Staphylococcal infections are often hard to treat due to increasing resistance, especially to β-lactams. Previous studies described the synergy between common antibiotics and isoflavonoids; however, little is yet known about the combinatory effects of antibiotics with products of human isoflavone metabolism. In this study, demethyltexasin (DT), a human body metabolite of soybean isoflavones, was evaluated for its possible antistaphylococcal combinatory effect with amoxicillin and oxacillin. For comparison, common therapeutically used combination of amoxicillin/clavulanic acid was tested. DT showed strong synergistic interactions against most of Staphylococcus aureus strains when combined with amoxicillin (sum of fractional inhibitory concentrations [ΣFIC] 0.257-0.461) and oxacillin (ΣFIC 0.109-0.484). When oxacillin was combined with DT, resistance to this antibiotic was overcome in many cases. Moreover, antibiotic/DT combinations were effective mainly against methicillin-resistant S. aureus (MRSA); however, the commonly used drug amoxicillin/clavulanic acid was effective only against sensitive strains. Our results indicated DT as a compound able to act synergistically with β-lactams. In addition, some combinations are effective against MRSA and decrease staphylococcal resistance. To the best of our knowledge this is the first report of the antimicrobial synergistic effects of isoflavone human body metabolite with common antibiotics. DT seems to be a possible candidate for further research focused on antistaphylococcal drug development, especially against antibiotic-resistant strains.

• Klíčová slova
• antibiotic resistance, antimicrobial combinatory effect, checkerboard method, β-lactam antibiotics,
• MeSH
• amoxicilin farmakologie   MeSH
• antibakteriální látky farmakologie   MeSH
• fixní kombinace léků MeSH
• isoflavony farmakologie   MeSH
• kombinace amoxicilinu a kyseliny klavulanové farmakologie   MeSH
• lidé MeSH
• methicilin rezistentní Staphylococcus aureus účinky léků   růst a vývoj   MeSH
• mikrobiální testy citlivosti MeSH
• oxacilin farmakologie   MeSH
• rezistence na methicilin účinky léků   MeSH
• Staphylococcus aureus účinky léků   růst a vývoj   MeSH
• synergismus léků MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 6,7,4'-trihydroxyisoflavone MeSH Prohlížeč
• amoxicilin MeSH
• antibakteriální látky MeSH
• fixní kombinace léků MeSH
• isoflavony MeSH
• kombinace amoxicilinu a kyseliny klavulanové MeSH
• oxacilin MeSH

Enteric fever caused by Salmonella typhi has been the most crucial health issue in rural people, especially in Southeast Asia and Africa. Another disease, Salmonellosis, caused by a large group of bacteria of the genus Salmonella, cause substantial economic loss resulting from mortality and morbidity. Higher concentration and repeated use of antibiotics to treat these diseases will likely develop antibiotic resistance among the microbes. The nanoparticle has good penetration power and can kill microbes. Combining two strategies by using nanoparticles with antibiotics kills microbes and reduces the chances of the development of antibiotics resistance. Silver, Nickel, Copper, and Zinc oxide Nanoparticles were chemically synthesized and characterized in this study. Silver nanoparticles at a concentration of 10 µg/ml inhibit all the strains under study. In comparison, silver nanoparticles (16.90 µg/ml), Nickel nanoparticles (83 µg ml-1), Copper nanoparticles (249 µg ml-1), and Zinc oxide (1614 µg ml-1) along with 50 µg/ml cefixime gave maximum zone of inhibition of 35 mm, 19 mm, 31 mm and 23 mm respectively. The antimicrobial assay showed that silver nanoparticles presented good antibacterial performance against all multi-drug-resistant pathogenic Salmonella sp alone as well as in combinations. The present study proved that silver nanoparticles at the lowest concentration along with cefixime could be a possible alternative to control the multi-drug-resistant pathogens.

• Klíčová slova
• Ag, Antimicrobial, Cu, Ni, Salmonella enterica typhi, Synergistic, Zn,
• Publikační typ
• časopisecké články MeSH

Lack of leptin production in ob/ob mice results in obesity and prediabetes that could be partly reversed by leptin supplementation. In the hypothalamus, leptin supports the production of prolactin-releasing peptide (PrRP), an anorexigenic neuropeptide synthesized and active in the brain. In our recent studies, the palmitoylated PrRP analog palm11-PrRP31 showed a central anorexigenic effect after peripheral administration. This study investigates whether PrRP could compensate for the deficient leptin in ob/ob mice. In two separate experiments, palm11-PrRP31 (5 mg/kg) and leptin (5 or 10 μg/kg) were administered subcutaneously twice daily for 2 or 8 weeks to 8- (younger) or 16-(older) week-old ob/ob mice, respectively, either separately or in combination. The body weight decreasing effect of palm11-PrRP31 in both younger and older ob/ob mice was significantly powered by a subthreshold leptin dose, the combined effect could be then considered synergistic. Leptin and palm11-PrRP31 also synergistically lowered liver weight and blood glucose in younger ob/ob mice. Reduced liver weight was linked to decreased mRNA expression of lipogenic enzymes. In the hypothalamus of older ob/ob mice, two main leptin anorexigenic signaling pathways, namely, Janus kinase, signal transducer and activator of transcription-3 activation and AMP-activated protein kinase de-activation, were induced by leptin, palm11-PrRP31, and their combination. Thus, palm11-PrRP31 could partially compensate for leptin deficiency in ob/ob mice. In conclusion, the results demonstrate a synergistic effect of leptin and our lipidized palm11-PrRP31 analog.

• Klíčová slova
• hypothalamic leptin signaling, leptin, ob/ob mice, prolactin-releasing peptide,
• MeSH
• glukózový toleranční test MeSH
• hormon uvolňující prolaktin analogy a deriváty   chemie   farmakologie   terapeutické užití   MeSH
• játra účinky léků   metabolismus   MeSH
• leptin farmakologie   terapeutické užití   MeSH
• metabolické sítě a dráhy účinky léků   MeSH
• metabolismus lipidů účinky léků   MeSH
• myši obézní MeSH
• myši MeSH
• obezita farmakoterapie   metabolismus   MeSH
• přijímání potravy účinky léků   MeSH
• synergismus léků MeSH
• tělesná hmotnost účinky léků   MeSH
• tělesná teplota MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• hormon uvolňující prolaktin MeSH
• leptin MeSH
• palm11-PrRP31 MeSH Prohlížeč

Transport systems are developed to improve the solubility of the transported drug, increase its stability, enhance its pharmacological activity and target cancer while minimising side effects. In this work, nanoporous silica particles that can be functionalized and loaded with a large number of hydrophobic molecules are proposed. The designed system was modified with folic acid to target the folic acid receptors of cancer cells. This modification enabled a higher uptake of the drug by the cells. Hypericin was selected as a hydrophobic molecule/drug with photodynamic properties suitable for diagnosis and therapy. Fluorescence microscopy and flow cytometry were used to detect the targeting and distribution of hypericin in the cancer cells. Furthermore, the combination of folic acid and hypericin has been shown to form singlet oxygen and to have a synergistic effect in improving the efficacy of photodynamic therapy. The functionalisation of the particles proposed in this work holds great potential for the delivery of hydrophobic drugs to other types of cancer cells with increased expression of the folic acid receptor to which the particles can be attached.

• Klíčová slova
• Folate receptors, Hypericin, Mesoporous silica, Photodynamic therapy, SBA-15, Targeting, Transport,
• MeSH
• anthraceny * MeSH
• folátové receptory zakotvené GPI metabolismus   MeSH
• fotochemoterapie * MeSH
• fotosenzibilizující látky * farmakologie   chemie   MeSH
• hydrofobní a hydrofilní interakce MeSH
• kyselina listová * chemie   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nanočástice chemie   MeSH
• oxid křemičitý chemie   MeSH
• perylen * analogy a deriváty   farmakologie   chemie   MeSH
• singletový kyslík metabolismus   MeSH
• synergismus léků * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• anthraceny * MeSH
• folátové receptory zakotvené GPI MeSH
• fotosenzibilizující látky * MeSH
• hypericin MeSH Prohlížeč
• kyselina listová * MeSH
• oxid křemičitý MeSH
• perylen * MeSH
• singletový kyslík MeSH

A single-dose simultaneous application of methotrexate (MTX; 0.002/microgram ml-1) and cisplatin (cis-Pt; 0.0002/microgram ml-1) had a permanent synergistic effect on both synchronized and asynchronous cell populations of V 79B cells. Successive combination of the drugs was manifested synergistically when MTX was applied first. The synchronized cell population was more sensitive to the cytostatics than the asynchronous population. Treatment with MTX alone, or the combination of MTX-cis-Pt, as well as their successive combination with the first drug being cis-Pt, caused gluconeogenesis.

• MeSH
• buněčné linie MeSH
• cisplatina farmakologie   MeSH
• glukoneogeneze účinky léků   MeSH
• křečci praví MeSH
• methotrexát farmakologie   MeSH
• plíce účinky léků   metabolismus   MeSH
• synergismus léků MeSH
• zvířata MeSH
• Check Tag
• křečci praví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• cisplatina MeSH
• methotrexát MeSH

Free radical scavengers like α-phenyl-N-tert-butylnitrone (PBN) and 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox) have been widely used as protective agents in various biomimetic and biological models. A series of three amphiphilic Trolox and PBN derivatives have been designed by adding to those molecules a perfluorinated chain as well as a sugar group in order to render them amphiphilic. In this work, we have studied the interactions between these derivatives and lipid membranes to understand how they influence their ability to prevent membrane lipid oxidation. We showed the derivatives better inhibited the AAPH-induced oxidation of 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLiPC) small unilamellar vesicles (SUVs) than the parent compounds. One of the derivatives, bearing both PBN and Trolox moieties on the same fluorinated carrier, exhibited a synergistic antioxidant effect by delaying the oxidation process. We next investigated the ability of the derivatives to interact with DLiPC membranes in order to better understand the differences observed regarding the antioxidant properties. Surface tension and fluorescence spectroscopy experiments revealed the derivatives exhibited the ability to form monolayers at the air/water interface and spontaneously penetrated lipid membranes, underlying pronounced hydrophobic properties in comparison to the parent compounds. We observed a correlation between the hydrophobic properties, the depth of penetration and the antioxidant properties and showed that the location of these derivatives in the membrane is a key parameter to rationalize their antioxidant efficiency. Molecular dynamics (MD) simulations supported the understanding of the mechanism of action, highlighting various key physical-chemical descriptors.

• Klíčová slova
• Amphiphilic nitrone, Antioxidant, Lipid oxidation, Model membranes, Synergism, Trolox,
• MeSH
• antioxidancia farmakologie   MeSH
• chromany (dihydrobenzopyrany) chemie   MeSH
• fluor chemie   MeSH
• membránové lipidy chemie   MeSH
• membrány umělé MeSH
• oxidace-redukce MeSH
• oxidy dusíku chemie   MeSH
• peroxidace lipidů MeSH
• synergismus léků MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid MeSH Prohlížeč
• antioxidancia MeSH
• chromany (dihydrobenzopyrany) MeSH
• fluor MeSH
• membránové lipidy MeSH
• membrány umělé MeSH
• nitrones MeSH Prohlížeč
• oxidy dusíku MeSH