1,721,084 research outputs found
Phytochemical, antimicrobial and antiplasmodial investigations on Guinean plant species
No full textAbstract: Medicinal plants have historically proven their value as sources of molecules with therapeutic potential, and nowadays still represent an interesting pool for the discovery of novel drug leads. Current research in drug discovery from medicinal plants involves a multifaceted approach combining several methods and techniques. Despite the considerable progress in terms of research and development of new treatment and prevention procedures over the last decades, infectious diseases still remain the leading cause of death in many developing countries. In Guinea, medicinal plants play an important role in the management of infectious diseases including malaria, urinary disorders, skin diseases and oral diseases. As part of a valorization program of these plant species, ethnopharmacological investigations have been carried out and plants species employed for the treatment of malaria, skin diseases, oral diseases and urinary disorders were inventoried. An extensive bibliographic review, followed by a preliminary biological screening resulted in the selection of some promising plant species including Terminalia albida, Tetracera alnifolia Combretum paniculatum and Pavetta crassipes. In the present research, we propose to deepen the biological and phytochemical investigations on some promising plants extracts, through the evaluation of their potential antimicrobial and antiplasmodial properties, and the corresponding active constituents. The bioassay-guided fractionation of Terminalia albida root resulted in the isolation of 14 compounds (1\u201314), and their antimicrobial properties were evaluated against Plasmodium falciparum, Candida albicans, Staphylococcus aureus and Escherichia coli. Pantolactone (IC50 0.60 \ub1 0.03 ?M) demonstrated significant activity against P. falciparum. Other compounds, including 3,4,3\u2019-tri-O-methyl-ellagic acid, the triterpenes arjunolic acid, arjungenin, arjunic acid and arjunglucoside II, and the phenol glycoside calophymembranside-B, were less active and showed IC50 values in the range 5 \u2013 15 ?M. None of the tested compound showed antibacterial or antifungal activity. Although the n-butanolic fraction was not active, the possibility cannot be excluded that this polar fraction contains inactive glycosides, which may release active aglycones after removal of the glycosidic moieties in the gastrointestinal tract, more in particular in the colon. Therefore, the n-butanolic fraction of the total root extract of Terminalia albida has been subjected to extensive dereplication studies followed by the isolation of the target compounds. As a result, 10 oleanane triterpenoids (1-10), among which six new compounds, i.e. albidanoside A, albidic acid A, albidinolic acid, albidienic acid, albidolic acid, albidiolic acid; two triterpene aglycones, i.e. albidic acid B and albidic acid C isolated here for the first time from a natural source; and two known compounds. Isolated compounds were evaluated for their antiplasmodial and antimicrobial activity against the chloroquine-resistant strain Plasmodium falciparum K1, Candida albicans and Staphylococcus aureus. Compounds 1 - 4, 6 ,7 and 8 demonstrated moderate antiplasmodial activity with IC50 values between 5 and 15 ?M. None of the tested compounds was active against C. albicans or S. aureus. These findings emphasize the potential of T. albida as a source for discovery of new antiplasmodial compounds. The bioassay-guided fractionation of Tetracera alnifolia leaves extracts led to the isolation of 19 compounds (1\u201319). Purification of fractions was performed by flash chromatography, followed by semi-preparative HPLC-DAD-MS and LC-SPE-NMR, while the structural elucidation of the isolated compounds was carried out by 1D and 2D NMR and HR-ESI-MS. Isolated compounds were screened against Plasmodium falciparum, Candida albicans and their cytotoxicity against MRC-5 cells was determined. The highest antiplasmodial activity was obtained for pheophorbide-b methyl ester (1.0 \ub1 0.7 ?M), (1,2)-bis-nor-phytone (2.0 ?M), isophytol (4.0 ?M) , pheophorbide-a methyl ester (2.8 \ub1 1.2 ?M), epicatechin-3-galloylester (5.5 \ub1 2.1), and phytol (6.9 \ub1 2.4 ?M). Other compounds, including myricetin-3-O-rhamnopyranoside, ?-tocopherol and cycloart-24-en-3?-yl ?-linolenate were less active and showed IC50 values in the range 13.5\u2013 25 ?M. None of the tested compounds was active against Candida albicans. A hight cytotoxicity was found for pheophorbide-b methyl ester, pheophorbide-a methyl ester and phytol. Nowadays, the rapid development of modern analytical techniques and various chemometric approaches provide new perspectives for early metabolite identification in natural products research. These techniques represent a potential strategy to streamline the traditional and laborious process of isolating natural products through targeting of unknown active compounds before purification. These innovative techniques have been applied on extracts of the leaves of C. paniculatum, which have demonstrated promising antiplasmodial activity during our preliminary studies, leading to a quick and effective identification of compounds correlated to this activity. The fractionation of crude extracts was carried out, followed by multivariate data analysis of liquid chromatography\u2013high resolution mass spectrometry (LC\u2013HRMS) profiles of the fractions obtained. In parallel, all fractions were screened against Plasmodium falciparum, and their cytotoxicity against MRC-5 cells was determined. Dereplication studies combining UPLC-MS/MS-based molecular networking, in silico analysis and NMR methods were employed to identify the important metabolites. Several compounds strongly correlated with antiplasmodial activity have been highlighted. Six compounds including rutin (IC50 6.7 ?M) and foliasalacioside F (IC50 10.6 ?M ) have been isolated and their OPLS predicted score values were in agreement with antiplasmodial results found in vitro. These preliminary results provided clear evidence on the effectiveness of using these innovative methods (chemometrics and dereplication analysis) for the rapid identification of active metabolites in plant extracts. Further research aiming for the isolating of additional promising compounds which have shown a strong correlation with antiplasmodial activity is ongoing
Phytochemical and analytical research on some medicinal plants from Panama using a metabolomics approach : **Cecropia** spp. and **Crescentia cujete**
No full textAbstract: Herbal medicines are described as any form of plant or plant product used in the maintenance of health as well as in the prevention, improvement, diagnosis or treatment of diseases. Due to the growing relevance of these products, we aimed to contribute to the development of scientifically based and quality controlled herbal substances. Some species of the genus Cecropia (Urticaceae) and Crescentia cujete (Bignonaceae) collected in Panama were selected as case study. Although food supplement-derived products from these plant species are commercially available, a comprehensive description of their phytochemical composition and appropriate analytical methods for guaranteeing their quality and safety are still lacking. A detailed phytochemical investigation on 4 Cecropia species led to the full identification or tentative characterization of 47 compounds, including 2 phenolic acids, 33 flavonoids, 3 flavonolignans and 9 triterpenoid saponins. Among these, two new antiplasmodial flavonolignans were isolated from C. obtusifolia and identified as ent-mururin A and ent-vaccinin A. The conditions for the extraction of chlorogenic acid, total flavonoids and flavonolignans from leaves of Cecropia species were optimized by using a design of experiment (DOE). A HPLC-DAD method for the quantification of these chemical markers was validated according to the ICH guidelines. The multivariate data analysis of the Cecropia species under investigation revealed the implications for phytochemical analysis in further taxonomic studies. The gastrointestinal and colonic biotransformation of the crude extract of the leaves of C. obtusifolia, was investigated under in vitro conditions, and the processing and interpretation of results were facilitated by using an automated machine-learning model. This investigation revealed that flavone C-glycosides and flavonolignans were stable throughout their passage in the simulated gastrointestinal tract including the colon phase. On the other hand, the colon bacteria extensively metabolized chlorogenic acid, flavonol and triterpenoid O-glycosides. An untargeted metabolomics approach combining UPLC-MS/MS-based molecular networking with conventional isolation and NMR methods was carried out for the phytochemical profiling of the fruit pulp of Crescentia cujete. Sixty-six products, including 9 n-alkyl glycosides, 23 phenolic acid derivatives (such as cinnamoyl and benzoyl derivatives), 15 flavonoids, 4 phenylethanoid derivatives and 15 iridoid glycosides were fully or tentatively identified. Among these, 8-epi-eranthemoside, crescentiol A and crescentiol B were reported as three new iridoid glucosides. In view of future work, the implementation of the validated analytical methods for the quantification of markers in Cecropia spp. and Crescentia cujete will be a great help for chemical standardization and authentication of their commercial derived products
Natural products as potential inhibitors of Advanced Glycation Endproducts (AGEs) and modulators of autophagy
No full textAbstract: Al eeuwenlang voorzien geneeskrachtige planten de menselijke beschaving van remedies voor het behoud van de gezondheid en de bestrijding van ziekten. Tegenwoordig zijn natuurlijke bronnen nog steeds een startpunt voor het onderzoek naar geneesmiddelen. Ze trekken de aandacht voor hun potenti\ueble toepassing als nieuwe therapeutische middelen bij de behandeling van hedendaagse ziekten met grote sociale en economische gevolgen, zoals diabetes type 2, hart- en vaatziekten). Er zijn verschillende mechanismen voorgesteld om de oorzaak van chronische aandoeningen te verklaren, en op biochemisch niveau correleert de eiwitglycatie (vorming van geavanceerde glycatie-eindproducten (AGEs)) met vele pathologische complicaties. Net als bij AGEs is autofagie in verband gebracht met een groot aantal pathologie\uebn, waaronder hartziekten, kanker, neurodegeneratie, infectieziekten, diabetes en auto-immuunziekten. Daarom vertegenwoordigen AGEs en autofagie nieuwe therapeutische doelwitten in het onderzoek naar natuurlijke producten. Het doel van dit doctoraatsproject was het isoleren en identificeren van verschillende geselecteerde klassen van natuurlijke producten (polymethoxyflavono\uefden (PMFs), biflavono\uefden, quinazolinealkalo\uefden) uit vier verschillende plantensoorten: Citrus sinensis, Citrus depressa, Ginkgo biloba en Adhatoda vasica. Vervolgens werden hun eigenschappen als AGEs remmers en autofagie modulatoren ge\uebvalueerd door middel van een reeks experimentele procedures. Het project omvatte gedetailleerd fytochemisch onderzoek door middel van verschillende chromatografische technieken: open kolom, flash en semi-preparatieve vloeistofchromatografie. De structuur van de verbindingen werd opgehelderd door 1D- en 2D- NMR-spectroscopie en massaspectrometrie. De preliminaire tests voor AGEs remmende eigenschappen van de verkregen zuivere verbindingen omvatten de runderserumalbumine (BSA) / glucose test, en evaluatie van de vorming van fructosamine-adducten en alfa-dicarbonylverbindingen. Omwille van bepaalde beperkingen van deze standaardmethoden werd een methode ontwikkeld om van niet-selectieve colorimetrische /fluorimetrische technieken te evolueren naar een meer betrouwbare methode op basis van chromatografie. Een HILIC UPLC/MS-methode moest worden ontwikkeld en gevalideerd, en werd daarna gebruikt om de AGEs remmende eigenschappen van enkel zuivere verbindingen en commercieel beschikbare standaarden te onderzoeken . Om de autofagie modulatie door enkele ge\uefsoleerde zuivere verbindingen en commerci\ueble standaarden te evalueren, werden verschillende testen gebruikt: LC3 detectie en kwantificering door western blot analyse, en de Cyto-ID autofagie detectie kit. Als onderdeel van het analytische werk werd een methode ontwikkeld en gevalideerd voor de kwantificering van vasicine - het belangrijkste chinazolinealkalo\uefde in de bladeren van Adhatoda vasica. Daarnaast werd de vastgestelde methode toegepast voor de kwaliteitscontrole van in de handel verkrijgbare kruidenproducten die Adhatoda poeder of -extract bevatten. In het algemeen zijn geavanceerde glycatie en modulatie van autofagie belangrijke oorzaken voor de progressie en pathogenese van veel chronische ziekten, en daarom kan het gebruik van gevalideerde methoden en technieken bijdragen tot de ondubbelzinnige ontdekking van nieuwe krachtige anti-AGEs en autofagie \uadmodulerende middelen
Contact allergy caused by natural and synthetic components in medical devices, adhesives in particular
No full textAbstract: The number and use of \u201cmedical devices\u201d is increasing rapidly in several para(medical) disciplines. These devices are used to aid in the diagnosis, treatment, monitoring and prevention of several human diseases. Although they are of great importance in health care, adverse cutaneous reactions, including allergic contact dermatitis (ACD), may occur when using them. Such allergic skin reactions can be caused by particular chemicals present in these devices, adhesives in particular, i.e., synthetic substances (e.g., \u201cacrylates\u201d and \u201cisocyanates\u201d), natural components (e.g., \u201ccolophonium\u201d, \u201cterpenes such as D-limonene\u201d and \u201csesquiterpene lactones\u201d) or other substances (e.g., sulphites). A well-known and recent example are contact-allergic skin reactions caused by acrylates, such as isobornyl acrylate (IBOA), used as adhesives (tackifiers) in glucose sensors (e.g., Freestyle\uae Libre) and insulin infusion sets (pumps), used by many diabetes patients worldwide. This research project concerns a cooperation between a chemical analytical laboratory (NatuRA, University of Antwerp) and a clinical department (Dermatology, University Hospital Antwerp/UZA). Apart from giving a general overview of contact allergies from medical devices (epidemiology), the main objective of this project is to reveal the (qualitative/quantitative) presence of some important contact allergens in particular types of medical devices, notably by means of chemical analyses, including, among others, gas chromatography-mass spectrometry (GC/MS). Furthermore, we aim to give insights into optimization of patch test preparations with (some of) the identified substances (e.g., how to patch test them, how to interpret results). Such patch tests are important diagnostic skin tests that can be used in the clinic to diagnose ACD caused by medical devices
Advancing the Zebrafish Embryo Developmental Toxicity Assay (ZEDTA) towards a sensitive screening assay
No full textAbstract: Within Europe, new approach methodologies (NAMs) for toxicity assessment of xenobiotics become very important. Several pharmaceutical, (agro)chemical and cosmetic companies are currently using zebrafish embryo assays as an alternative for animal testing to screen new compounds for developmental toxicity. The zebrafish embryo assay is considered to be very promising, as it is the only non-animal assay that allows assessment of a vertebrate model during the main organogenesis period with a relatively high accuracy. However, it still suffers from some limitations. Inter- and intra-laboratory discordances in teratogenicity classification of identical compounds, as well as false negative and false positive results are reported for known mammalian teratogens and non-teratogens, respectively. In view of human safety, false negative results are more critical than false positive results, as teratogens may be missed. Causes for these false negative results include: inter-species differences in mode of action, issues with compound uptake, the limited biotransformation capacity and the limited number of morphological endpoints in zebrafish embryo assays. Therefore, the aim of this doctoral thesis was to further standardize and optimize the Zebrafish Embryo Developmental Toxicity Assay (ZEDTA) in order to increase the sensitivity of this screening assay, and as such better predict birth defects caused by drugs during the first trimester of pregnancy. To do so, we: 1) developed a standardized ZEDTA protocol that can be extended with a metabolic activation system, 2) determined the maximal concentration of DMSO that can be safely used as a solvent in the ZEDTA, 3) investigated whether the sensitivity of the ZEDTA could be increased by including a skeletal staining method, and 4) investigated whether anti-epileptic drugs that require bioactivation to exert their teratogenic potential are biotransformed by non-CYP enzymes in zebrafish embryos and young larvae, and whether these metabolites cause developmental toxicity
Biotechnological and phytochemical investigations on antitumoral and antigenotoxic plant species
No full textAbstract: abstract not availabl
Bioactivation of human proteratogens in the zebrafish embryo model, a new approach method (NAM) for developmental toxicity assessment
No full textAbstract: Over the past two decades, zebrafish (Danio rerio) embryos have garnered considerable attention as an alternative model for developmental toxicity testing, offering a cost-effective, time-efficient, and ethically favorable substitute to traditional animal studies that demand extensive monitoring and involve large numbers of animals. Zebrafish offer numerous advantages and are classified as an in vitro model up to the free-feeding stage (120 hours post-fertilization, hpf) under European regulations. However, further characterization of this model, including its xenobiotic-metabolizing capacity, is essential for a more comprehensive understanding of its applicability to human safety assessment. This research project focusses on a detailed characterization of the transcript profiling of key enzymes involved in xenobiotic metabolism, such as cytochrome P450 (CYP) enzymes, during zebrafish development up to the juvenile stage. This was achieved through quantitative PCR on mRNA extracted from pooled organisms. Additionally, we investigated the ability of zebrafish embryos/larvae (from 5.25 to 120 hpf) to metabolize two known mammalian proteratogens, carbamazepine (CBZ) and phenytoin (PHE), into their respective mammalian active metabolites: carbamazepine-10,11-epoxide (E-CBZ) and 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH). This was done using an ultra-performance liquid chromatography-triple quadrupole mass spectrometry investigation. The gross morphology of the embryos and larvae exposed to these compounds was also observed under a microscope during development. Subsequently, we explored ways to improve the Zebrafish Embryo Developmental Toxicity Assay (ZEDTA) by incorporating a metabolic activation system through a preincubation strategy. Our CYP ontogeny investigation revealed that CYP1-3 mRNA expression levels were low until 72 hpf, after which they increased and reached a plateau around 120 hpf. Accordingly, the biotransformation investigation showed that zebrafish embryos started to metabolize CBZ into E-CBZ around 96 hpf, but no conversion of PHE to HPPH was detected. In addition, exposure of zebrafish embryos to CBZ and PHE resulted in teratogenic effects, although these were not observed for the mammalian teratogenic metabolites. The enhancements made to the ZEDTA, including centrifugation and dilution steps in the preincubation medium, enables exposure of embryos to the parent compound and their potential metabolites until 120 hpf. Overall, our findings indicate that zebrafish embryos possess a moderate xenobiotics metabolization capacity by the end of organogenesis. Teratogenicity in zebrafish may follow different pathways compared to mammalian species and further characterization of other key metabolic enzymes is necessary before this model can be validated. However, the scientific community is shifting toward combining New Alternative Methods with mechanistic investigations, rather than relying solely on the ZEDTA
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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