Biological potential and chemical profile of methanolic extracts of herbs Anthriscus cerefolium (L.) Hoffm. (Apiaceae), Ononis spinosa L. (Fabaceae) and Phlomis fruticosa L. (Lamiaceae)

Upotreba biljaka u lečenju ljudi datira još od antičkih vremena. Danas, savremena nauka izučava lekovita svojstva biljaka, potvrđuje njihov etnobotanički značaj i opisuje nove upotrebe biljnih vrsta kao medicinskih sredstava. Cilj ove doktorske disertacije je analiza biološkog potencijala i hemijskog profila metanolnih ekstrakata dobijenih iz nadzemnih delova biljaka Anthriscus cerefolium, Ononis spinosa i Phlomis fruticosa. Biološki potencijal metanolnih ekstrakata je određen testiranjem antibakterijske, antifungalne, antibiofilm, antioksidativne, enzim-inhibitorne, antiproliferativne i anti-inflamatorne aktivnosti. Predstavljen je i uvid u mehanizme antibakterijskog, antifungalnog i antiproliferativnog delovanja ekstrakata. Dobijeni rezultati su ukazali na značajnu antimikrobnu aktivnost ekstrakata protiv patogenih bakterija i gljiva. Takođe, ekstrakti su posedovali antibiofilm aktivnost protiv biofilma bakterija i patogenih kvasnica, kao i aktivnost na neke od faktora virulencije bakterija i kvasnica. Dalje, uočen je značajan antioksidativni potencijal svih ekstrakata, kao i njihova sposobnost inhibicije medicinski važnih enzima. Testirani ekstrakti nisu pokazali toksičnost prema ne-tumorskim humanim primarnim ćelijama, ali su pokazali antiproliferativno dejstvo na tumorske ćelijske linije. Takođe, uočene su i promene morfologije ćelija glioblastoma tretiranih ekstraktom A. cerefoilum. Ekstrakti su pokazali anti-inflamatornu aktivnost na in vitro modelu bakterijski indukovane inflamacije kod humanih keratinocita kože. Takođe, u okviru ove doktorske disertacije rasvetljen je hemijski sastav polifenola u testiranim ekstraktima i utvrđeno je da dominiraju derivati fenolnih kiselina i flavonoida.The use of plants in ethnomedicine dates back to ancient times. Today, modern science explores the healing properties of plants, confirms their ethnobotanical significance and describes new uses of plant species as medicinal agents. The aim of this dissertation is to analyze the biological potential and chemical profile of methanolic extracts obtained from the herbs Anthriscus cerefolium, Ononis spinosa and Phlomis fruticosa. The biological potential of methanolic extracts was determined by testing antibacterial, antifungal, antibiofilm, antioxidant, enzyme-inhibitory, antiproliferative and anti-inflammatory activities. An insight into the mechanisms of antibacterial, antifungal and antiproliferative actions was also presented. The chemical composition of methanol extracts has been studied both qualitatively and quantitatively. The obtained results indicated significant antimicrobial activity of the extracts against pathogenic bacteria and fungi. Also, the extracts possessed antibiofilm activity against bacterial and yeasts biofilms, as well as the activity on some of the virulence factors of bacteria and yeasts. Furthermore, significant antioxidant potential of all extracts was observed, as well as their ability to inhibit medically important enzymes. The extracts did not show toxicity to human primary cells, but showed antiproliferative effect on tested tumor cell lines. Also, the changes in the morphology of glioblastoma cells treated with the methanol extract of A. cerefoilum were observed. The extracts showed anti-inflammatory activity in in vitro model of bacterial-induced inflammation of human skin keratinocytes. Furthermore, the chemical composition of polyphenols in the tested extracts was clarified and was determined that derivatives of phenolic acids and flavonoids dominate

Medicinal chemistry from fungi and back: discovery of novel anti-fungal drugs and mycotherapy of cancer and other diseases with fungal metabolites

Fungi are important organisms for human population and could find important applications namely, in many pharmaceutical and food industries. A variety of compounds has been isolated from medicinal and edible mushrooms, and their healthbeneficial effects have been reported. On the other hand, it is important to control microfungi as parasites and contaminants since they can provoke, in some cases, serious issues to human health. The following issue is devoted to recent findings in the fields of novel antifungal drugs, mycotherapy of cancer and other diseases with compounds recently isolated from fungi. It is covered by eight hot topic manuscripts from the mentioned relevant fields. A review on antifungal activity of mushrooms (Basidiomycetes) and their isolated compounds including high (e.g. peptides and proteins) and low (e.g. sesquiterpenes and other terpenes, steroids, organic acids, acylcyclopentenediones and quinolines) molecular weight compounds is presented. Furthermore, antioxidant protective effects of mushroom metabolites is presented covering antioxidant features of numerous compounds isolated from mushrooms, such as phenolic compounds, vitamins, polysaccharides, peptides, proteins, organic acids, carotenoids, alkaloids, and nucleotides. Cyclodextrins are usually used in antifungal formulations as auxiliary substances to improve solubility, stability, or other physicochemical properties of the active compound. Nevertheless, recent research and practical use results indicate that cyclodextrins might also act as active compounds in pharmaceutical formulations. Furthermore, Recent advances in synthesis of compounds and their biological evaluation considering antifungal activity is also presented, covering the broad spectrum of compounds from different chemical classes. Therapeutic properties of mushrooms in managing adverse effects in the metabolic syndrome deeply discusses the use of edible mushrooms, their extracts, polysaccharide fractions and isolated compounds as hypoglycaemic agents, as holders of cholesterol and triglyceride lowering ability, hypotensive agents, as well as weight managing holders. New and highly potent antitumor natural products from marine-derived fungi presents recent finding on cytotoxic activities of fungal compounds. Essential oils for the control of fungi and the production of aflatoxins, especially the most toxic aflatoxins B1 and G1, is essential and decisive, therefore highlighting the possibilities of utilizing essential oils in biological control of aflatoxin contamination. The last paper focuses on recent update of cytotoxic and antitumor activity of mushroom extracts and compounds belonging to the heteropolysaccharides, β-glucans, α-glucans, proteins, complexes of polysaccharides with proteins, fatty acids, nucleoside antagonists, terpenoids, sesquiterpenes, lanostanoids, sterols and phenolic compounds. Molecular mechanisms of cytotoxic and antitumor activities are briefly discussed

Evaporation of a black hole off of a tense brane

We calculate the gray-body factors for scalar, vector and graviton fields in the background of an exact black hole localized on a tensional 3-brane in a world with two large extra dimensions. Finite brane tension modifies the standard results for the case with of a black hole on a brane with negligible tension. For a black hole of a fixed mass, the power carried away into the bulk diminishes as the tension increases, because the effective Planck constant, and therefore entropy of a fixed mass black hole, increase. In this limit, the semiclassical description of black hole decay becomes more reliable.Comment: a few typos corrected, accepted for publication in PR

Razvoj sistema odbrane Republike Srbije u uslovima hibridnih pretnji

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Black Hole as a Point Radiator and Recoil Effect on the Brane World

A small black hole attached to a brane in a higher dimensional space emitting quanta into the bulk may leave the brane as a result of a recoil. We construct a field theory model in which such a black hole is described as a massive scalar particle with internal degrees of freedom. In this model, the probability of transition between the different internal levels followed by emission of massless quanta is identical to the probability of thermal emission calculated for the Schwarzschild black hole. The discussed recoil effect implies that the thermal emission of the black holes, which might be created by interaction of high energy particles in colliders, could be terminated and the energy non-conservation can be observed in the brane experiments.Comment: 4 pages, 1 figure, accepted for publication in Phys. Rev. Letter

Strategic environment influence on development of defense of the Republic of Serbia

Strategic environment of the Republic of Serbia is determined by the operation of a large number of factors, which affect the defense system and its development in various ways. In the area of development planning of the defense system, the overriding purpose of analysis and assessment of the strategic environment is review and cogitation of phenomena and trends, and their influence on the development of the defense system. This paper analyzes the basic phenomena and trends in the field of strategic environmental factors and their individual, as well as hybrid, impact on the development of the defense system. For the sake of predictable and successful implementation of the defense system purpose, defense planning holders pay special attention to the analysis and assessment of the strategic environmental factors such as security, political, economic, social, technological, informational, ecological, and others. Strategic environmental factors are interdependent and connected, and they make an inseparable whole - the reality that affects functioning and development of the defense system. Knowledge and experience of defense analysts and planners is important for the quality assessment of the strategic environment impact and in the end it is crucial for proposing management decisions in order to ensure the effective functioning and development of the defense system. In the process, the application of scientific and field-proven methods, tools and techniques is inevitable. Study of the strategic environment impact creates the conditions for continuous and preventive action for timely adjustment of the defense system to new circumstances, thus enabling the successful execution of the defense tasks and protection of the defense interests

Polyphenols as Inhibitors of Antibiotic Resistant Bacteria-Mechanisms Underlying Rutin Interference with Bacterial Virulence

The rising incidence of antibiotic resistant microorganisms urges novel antimicrobials development with polyphenols as appealing potential therapeutics. We aimed to reveal the most promising polyphenols among hesperetin, hesperidin, naringenin, naringin, taxifolin, rutin, isoquercitrin, morin, chlorogenic acid, ferulic acid, p-coumaric acid, and gallic acid based on antimicrobial capacity, antibiofilm potential, and lack of cytotoxicity towards HaCaT, and to further test its antivirulence mechanisms. Although the majority of studied polyphenols were able to inhibit bacterial growth and biofilm formation, the most promising activities were observed for rutin. Further investigation proved rutin's ability to prevent/eradicate Pseudomonas aeruginosa and MRSA urinary catheter biofilms. Besides reduction of biofilm biomass, rutin antibiofilm mechanisms included reduction of cell viability, exopolysaccharide, and extracellular DNA levels. Moderate reduction of bacterial adhesion to human keratinocytes upon treatment was observed. Rutin antivirulence mechanisms included an impact on P. aeruginosa protease, pyocyanin, rhamnolipid, and elastase production and the downregulation of the lasI, lasR, rhlI, rhlR, pqsA and mvfR genes. Rutin also interfered with membrane permeability. Polyphenols could repress antibiotic resistant bacteria. Rutin has shown wide antimicrobial and antibiofilm capacity employing a range of mechanisms that might be used for the development of novel antimicrobials

Nutritional value, chemical composition, antioxidant activity and enrichment of cream cheese with chestnut mushroom Agrocybe aegerita (Brig.) Sing

A very well-known and appreciated mushroom, Agrocybe aegerita (Brig.) Sing, was the subject of chemical profiling, antioxidant assays and sensory evaluation test in creamcheese. Methanolic extract obtained from a wild sample of A. aegerita fruiting body was fully chemically identified. Sample was found to be rich in carbohydrates (84.51 g/ 100 g dw), ash and proteins (6.69 g/100 g dw and 6.68 g/ 100 g dw, respectively). Trehalose was the main free sugar while malic acid was the most abundant organic acid. Four isoforms of tocopherols were identified; γ- tocopherol was the dominant isoform with 86.08 μg/100 g dw, followed by β- tocopherol, δ-tocopherol and α-tocopherol (8.80 μg/ 100 g dw, 3.40 μg/100 g dw and 2.10 μg/100 g dw, respectively). Polyunsaturated fatty acids were predominant, with linoleic acid as the most prominent one (78.40 %). Methanolic extract of chestnut mushroom exhibited high antioxidant activity. Sensory evaluation test included grading by panelists and comparing the overall acceptability of cream cheese alone and enriched cream cheese with dry powder of A. aegerita. General conclusion of the participants was that the newly developed product was more likeable in comparison to cream cheese alone. Due to the health-beneficial effects of antioxidants and wealth of chemically identified nutrients, A. aegerita is a promising starting material for incorporation on larger scale products

Chemical Composition, Antimicrobial and Antiradical Properties of the Essential Oils of Seseli globiferum Fruits

The chemical composition and antimicrobial and antiradical activities of the essential oils isolated from unripe and ripe fruits of S. globiferum Vis. (Apiaceae) have been determined. The most abundant constituent in the essential oils of unripe and ripe fruits was sabinene (53.1% and 65.3%), followed by gamma-terpinene (7.7% and 6.6%), alpha-pinene (7.2% and 4.4%), and beta-phellandrene (5.0% and 4.9%). Antibacterial and antifungal properties of these oils were evaluated using a modified microdilution technique. Scavenging activity was determined by the DPPH radical assay. The essential oils exhibited significant antimicrobial, but low antiradical activity

Antibacterial activity of Veronica montana L. extract and of protocatechuic acid incorporated in a food system

This study was designed to evaluate the antibacterial activity of the Veronica montana L. water extract and its main phenolic compound, protocatechuic acid. The antibacterial activity was determined by microdilution assay against six strains of Gram-positive and Gram-negative bacteria. Listeria monocytogenes was the most sensitive of the tested bacterial species. Antibacterial preserving properties of protocatechuic acid were also evaluated after its incorporation in cream cheese, using L. monocytogenes as commonly cheese contaminant. The compound successfully inhibited L. monocytogenes development in cream cheese, at room temperature and in refrigerator (25 °C and 4 °C, respectively), after 3 days of inoculation. Sensory evaluation was carried out in order to validate the mentioned food system. A possible mode of action of the tested compound towards bacterial cells was assessed and appears to be direct lysis of pathogenic cytoplasmic membrane. Prediction of pharmacokinetic properties was also performed using computational analyzes. The obtained results can serve as an important platform for the development of effective natural preservativesSerbian Ministry of Education and Science for financial support (grant numbers 173032, 46013)