Maria Teresa Batista

University of Coimbra, Coímbra, Coimbra, Portugal

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Publications (28)38.92 Total impact

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    ABSTRACT: Alzheimer's disease (AD) neuropathology is strongly associated with the activation of inflammatory pathways, and long-term use of anti-inflammatory drugs reduces the risk of developing the disease. In S. Tomé e Príncipe (STP), several medicinal plants are used both for their positive effects in the nervous system (treatment of mental disorders, analgesics) and their anti-inflammatory properties. The goal of this study was to determine whether a phenotypic, cell-based screening approach can be applied to selected plants from STP (Voacanga africana, Tarenna nitiduloides, Sacosperma paniculatum, Psychotria principensis, Psychotria subobliqua) in order to identify natural compounds with multiple biological activities of interest for AD therapeutics.
    Journal of ethnopharmacology. 06/2014;
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    ABSTRACT: Flavonoids from lemongrass – Cymbopogon citratus (DC.) Stapf – leaves infusion, a commonly consumed beverage for the treatment of inflammatory-related conditions, were investigated in this work. Luteolin O-, C- and O,C-glycosides were isolated and identified by nuclear magnetic resonance, being the cassiaoccidentalin B structure fully characterized for the first time in lemongrass. The anti-inflammatory activity of luteolin and its glycosides was evaluated in lipopolysaccharide-stimulated macrophages. Luteolin glycosides demonstrated less cytotoxicity than luteolin itself. Although glycosylation decreases luteolin anti-inflammatory properties, being higher to C-glycosylation, an inhibitory effect on inflammatory mediator production (nitric oxide and IL-1β) was verified for the luteolin 7-O-β-glucopyranoside, without cytotoxic effects. Therefore, luteolin glycosides from lemongrass infusion are evidenced as a less toxic alternative to current anti-inflammatory drugs with promising use in pharmaceutical and food supplement industries. Additionally, this work establishes structure–activity relationships, which constitutes valuable information in the design of anti-inflammatory luteolin glycosides devoid of toxicity.
    Journal of Functional Foods. 01/2014; 10:436–443.
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    ABSTRACT: ETHNOPHARMACOLOGICAL RELEVANCE: Propolis is a bee product with numerous biological and pharmacological properties, such as immunomodulatory and anti-inflammatory activities. It has been used in folk medicine as a healthy drink and in food to improve health and prevent inflammatory diseases. However, little is known about its mechanism of action. Thus, the goal of this study was to verify the antioxidant activity and to explore the anti-inflammatory properties of propolis by addressing its intracellular mechanism of action. Caffeic acid was investigated as a possible compound responsible for propolis action. MATERIALS AND METHODS: The antioxidant properties of propolis and caffeic acid were evaluated by using the 2,2-diphenyl-1-picrylhydrazyl free radical (DPPH) scavenging method. To analyze the anti-inflammatory activity, Raw 264.7 macrophages were treated with different concentrations of propolis or caffeic acid, and nitric oxide (NO) production, a strong pro-inflammatory mediator, was evaluated by the Griess reaction. The concentrations of propolis and caffeic acid that inhibited NO production were evaluated on intracellular signaling pathways triggered during inflammation, namely p38 mitogen-activated protein kinase (MAPK), c-jun NH2-terminal kinase (JNK1/2), the transcription nuclear factor (NF)-κB and extracellular signal-regulated kinase (ERK1/2), through Western blot using specific antibodies. A possible effect of propolis on the cytotoxicity of hepatocytes was also evaluated, since this product can be used in human diets. RESULTS: Caffeic acid showed a higher antioxidant activity than propolis extract. Propolis and caffeic acid inhibited NO production in macrophages, at concentrations without cytotoxicity. Furthermore, both propolis and caffeic acid suppressed LPS-induced signaling pathways, namely p38 MAPK, JNK1/2 and NF-κB. ERK1/2 was not affected by propolis extract and caffeic acid. In addition, propolis and caffeic acid did not induce hepatotoxicity at concentrations with strong anti-inflammatory potential. CONCLUSIONS: Propolis exerted an antioxidant and anti-inflammatory action and caffeic acid may be involved in its inhibitory effects on NO production and intracellular signaling cascades, suggesting its use as a natural source of safe anti-inflammatory drugs.
    Journal of ethnopharmacology 06/2013; · 2.32 Impact Factor
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    ABSTRACT: ETHNOPHARMACOLOGICAL RELEVANCE: Cymbopogon citratus (DC) Stapf leaves infusion is used in traditional medicine for the treatment of inflammatory conditions, however little is known about their bio-active compounds. AIM OF THE STUDY: Investigate the compounds responsible for anti-inflammatory potential of Cymbopogon citratus (Cy) on cytokines production induced by lipopolysaccharide in human and mouse macrophages, and the action mechanisms involved. MATERIALS AND METHODS: An essential oil-free infusion of Cy was prepared and polyphenol-rich fractions (PFs) were obtained from it by column chromatography. Chlorogenic acid was identified, by HPLC/PDA/ESI-MS(n). The expression of cytokines, namely TNF-α and CCL5, was analyzed by real-time RT-PCR, on lipopolysaccharide-stimulated human macrophages. Activation of nuclear factor-κB, a master regulator of inflammation, was investigated by Western blot and gene reporter assay. Proteasome activity was assessed using a fluorogenic peptide. RESULTS: Cymbopogon citratus extract and its polyphenols inhibited the cytokine production on human macrophages. This supports the anti-inflammatory activity of Cy polyphenols in physiologically relevant cells. Concerning the effect on the activation of nuclear factor (NF)-κB pathway, the results pointed to an inhibition of LPS-induced NF-κB activation by Cy and PFs. Chlorogenic acid was identified, by HPLC/PDA/ESI-MS(n), as the main phenolic acid of the Cy infusion, and it demonstrated to be, at least in part, responsible by that effect. Additionally, it was verified for the first time, that Cy and PFs inhibited the proteasome activity, a complex that controls NF-κB activation, having CGA a strong contribution. CONCLUSIONS: The results evidenced, for the first time, the anti-inflammatory properties of Cymbopogon citratus through proteasome inhibition and, consequently NF-κB pathway and cytokine expression. Additionally, Cy polyphenols, in particular chlorogenic acid, were highlighted as bio-active compounds.
    Journal of ethnopharmacology 04/2013; · 2.32 Impact Factor
  • III CEF Conference; 09/2012
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    ABSTRACT: Extensive research within the last two decades revealed that most chronic illnesses, including cancer, neurological, autoimmune and cardiovascular diseases are mediated through chronic inflammation. Thus, suppressing chronic inflammation has the potential to delay, prevent, and treat those diseases. However, side effects and high costs of current anti-inflammatory drugs force the development of new drugs. Natural products represent an important source of new bioactive compounds. Among them, phenolic compounds, which are widely distributed in plants, have been described as having many therapeutic effects. Several reviews have addressed the anti-inflammatory activity of phenols, attributing their properties not only to the antioxidant capacity, but also to inflammatory mediators' modulation, namely cytokines and pro-inflammatory proteins, such as inducible nitric oxide synthase and cyclooxygenase-2. Signal transduction pathways precede changes in inflammatory mediators' expression. However, only a restricted number of studies have addressed the effect of phenols on a specific signal transduction pathway. The present review attempts to summarize and highlight a broad range of inflammation-associated signaling pathways modulated by phenols namely: nuclear factor (NF)-κB, activator protein (AP)-1, peroxisome proliferator-activated receptor (PPAR) and nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factors; mitogen-activated protein kinases (MAPKs); protein tyrosine kinases (PTKs); tyrosine phosphatidylinositol 3-kinase (PI3K)/Akt and ubiquitin-proteasome system. As a consequence of phenols effect on signaling pathways, described above, their action on inflammatory mediators' production is mentioned. Finally, it is established that the structure-activity relationships of phenolic compounds are a valuable information source on the development of new anti-inflammatory drugs from natural products.
    Current Medicinal Chemistry 04/2012; 19(18):2876-900. · 3.72 Impact Factor
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    ABSTRACT: Objectives Pseudomonas aeruginosa (PA) is at present the fourth most common nosocomial pathogen, causing a wide variety of serious infections on compromised hosts and is characterized by an intrinsic resistance to various antimicrobial agents and for the ability to easily develop multi-drug resistance (MDR) under antibiotic pressure. Metallo-beta-lactamases (MBLs) confer a MDR profile to the bacteria that present them, since they hydrolyse all beta-lactams, except aztreonam. At present, there is no available inhibitor of MBLs, which augments the risk of infections caused by MBLs producing bacteria. Some polyphenols are generally recognised as quite potent antibiotics. The aim of this study was to challenge clinical isolates of MBL VIM-2 producers PA with an extract and polyphenol-rich fractions from strawberry (Fragaria vesca) leaves, in order to screen for antimicrobial activity, with the intent to find possible future therapeutic alternatives to treat MBL producing PA infections. Methods Fragaria vesca leaves (Fv) were extracted with ethanol (EtOH) and 50% aqueous EtOH. Three fractions from that crude extract were obtained on a Sephadex® LH-20 column by elution with 50% and 75% aqueous methanol (Fa and Fb, respectively) and 70% aqueous acetone (Fc). Fifteen MBL VIM-2 producers PA clinical isolates were used. Standard microplate assays were performed to determine MICs of extract (0.78 to 50 mg/ml) and fractions (0.39 to 25 mg/ml). Results Crude extract presented MIC50=10.35 mg/ml and MIC90=20.7 mg/ml. Fraction Fa presented MIC50 and MIC90 of 25 mg/ml; fraction Fb presented MIC50=6.25 mg/ml and MIC90=12.5 mg/ml; fraction Fc presented MIC50 and MIC90 of 12.5 mg/ml. The more active fraction was fraction Fb, essentially constituted by tannins: proanthocyanidins and ellagitannins. Curiously, an exacerbation of the pigment in all isolates was detected with this fraction. Conclusion A fraction of a crude extract obtained from Fragaria vesca leaves presented an interesting activity against MBL VIM-2 producers PA clinical isolates. One or more polyphenols of this fraction can constitute a significant potential for the development of novel antibacterial therapies against these bacteria. Further studies are required to address this possibility. For an approach to antimicrobial efficacy, MDR clinical isolates should be used and not only ATCC strains, since they represent more accurately the pathovars of the species, which confers higher interest to the obtained results.
    22nd European Congress of Clinical Microbiology and Infectious Diseases, London, United Kingdom; 04/2012
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    ABSTRACT: Essential oils are known to possess antimicrobial activity against a wide spectrum of bacteria and fungi. In the present work the composition and the antifungal activity of the oils of Juniperus communis subsp. alpina (Suter) Čelak were evaluated. Moreover, the skin cytotoxicity, at concentrations showing significant antifungal activity, was also evaluated. The oils were isolated by hydrodistillation and analysed by gas chromatography and gas chromatography-mass spectrometry. Minimal inhibitory concentration (MIC) and minimal lethal concentration (MLC) were used to evaluate the antifungal activity of the oil against dermatophytes (Epidermophyton floccosum, Microsporum canis, M. gypseum, Trichophyton mentagrophytes, T. mentagrophytes var. interdigitale, T. rubrum, T. verrucosum), yeasts (Candida albicans, C. guillermondii, C. krusei, C. parapsilosis, C. tropicalis, Cryptococcus neoformans) and Aspergillus species (Aspergillus flavus, A. fumigatus, A. niger). Cytotoxicity was tested in HaCaT keratinocytes through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Essential oil of J. communis subsp. alpina needles was predominantly composed of monoterpene hydrocarbons (78.4%), with the main compounds being sabinene (26.2%), α-pinene (12-9%) and limonene (10.4%). Results concerning the antifungal activity demonstrated the potential of needle oil against dermatophytes, particularly for Microsporum canis and Trichophyton rubrum with MIC and MLC of 0.32 μL/mL. Furthermore, evaluation of cell viability showed no significant cytotoxicity in HaCaT keratinocytes at concentrations between 0.32 and 0.64 μL/mL. These results show that it is possible to find appropriate doses of J. communis subsp. alpina oil with both antifungal activity and a very low detrimental effect on keratinocytes. Copyright © 2012 John Wiley & Sons, Ltd.
    Phytotherapy Research 02/2012; 26(9):1352-7. · 2.07 Impact Factor
  • 5th International Congress on Ppolyphenols and Health; 10/2011
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    ABSTRACT: Leaves from cultivated Cymbopogon citratus were extracted with methanol, 80% aqueous ethanol and water (infusion and decoction) and the extracts were assessed for their antiradical capacity by 2,2-diphenyl-1-picrylhydrazyl (DPPH Å) assay; the infusion extract exhib-ited the strongest activity. Tannins, phenolic acids (caffeic and p-coumaric acid derivatives) and flavone glycosides (apigenin and luteolin derivatives) were identified in three different fractions obtained from an essential oil-free infusion, and a correlation with their scavenger capacity for reactive oxygen species was studied. The tannin and flavonoid fractions were the most active against species involved in oxidative damage processes. In the flavonoid fraction, representing 6.1% of the extract, thirteen compounds (O-and C-glycosylflavones) were tentatively identified by high performance liquid chromatography, coupled to photodiode-array and electrospray ionization mass spectrometry detectors (HPLC–PDA–ESI/MS), nine of which were identified for the first time in this plant, all of them being C-glyco-sylflavones (mono-C-, di-C-and O,C-diglycosylflavones). The potential beneficial and protective value of the identified polyphenols for human health is discussed.
    01/2011;
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    ABSTRACT: Aqueous extracts of Cymbopogon citratus (Cy) leaves are used in traditional medicine for the treatment of inflammatory conditions, however, little is known about their mechanism of action. The aim of this study is to explore the anti-inflammatory properties of Cymbopogon citratus leaves and their polyphenol-rich fractions (PFs), as well its mechanism of action in murine macrophages. A lipid- and essential oil-free infusion of Cy leaves was prepared (Cy extract) and fractionated by column chromatography. Anti-inflammatory properties of Cy extract (1.115 mg/ml) and its PFs, namely phenolic acids (530 μg/ml), flavonoids (97.5 μg/ml) and tannins (78 μg/ml), were investigated using lipopolysaccharide (LPS)-stimulated Raw 264.7 macrophages as in vitro model. As inflammatory parameters, nitric oxide (NO) production was evaluated by Griess reaction, as well as effects on cyclooxygenase-2 (COX-2), inducible NO synthase (iNOS) expression and on intracellular signaling pathways activation, which were analyzed by Western blot using specific antibodies. Cy extract inhibited iNOS expression, NO production and various LPS-induced pathways like p38 mitogen-activated protein kinase (MAPK), c-jun NH(2)-terminal kinase (JNK) 1/2 and the transcription nuclear factor (NF)-κB. The extracellular signal-regulated kinase (ERK) 1/2 and the phosphatidylinositol-3-kinase (PI3K)/Akt activation were not affected by Cy extract. Both phenolic acid- and tannin-rich fractions significantly inhibited NF-κB activation, iNOS expression and NO production but none of the PFs modulated MAPKs or PI3K/Akt activation. Neither Cy extract nor PFs affected LPS-induced COX-2 expression but LPS-induced PGE(2) production is inhibited by Cy extract and by phenolic acid-rich fraction. Our data provide evidence that support the usage of Cymbopogon citratus leaves extract in traditional medicine, and suggest that Cy, in particular its polyphenolic compounds, could constitute a natural source of a new and safe anti-inflammatory drug.
    Journal of ethnopharmacology 11/2010; 133(2):818-27. · 2.32 Impact Factor
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    ABSTRACT: Cymbopogon citratus, an herb known worldwide as lemongrass, is widely consumed as an aromatic drink, and its fresh and dried leaves are currently used in traditional cuisine. However, little is known about the mechanism of action of C. citratus, namely, the anti-inflammatory effects of its dietary components. Because nitric oxide (NO), produced in large quantities by activated inflammatory cells, has been demonstrated to be involved in the pathogenesis of acute and chronic inflammation, we evaluated the effects of the infusion of dried leaves from C. citratus, as well as its polyphenolic fractions--flavonoid-, tannin-, and phenolic acid-rich fractions (FF, TF, and PAF, respectively)--on the NO production induced by lipopolysaccharide (LPS) in a skin-derived dendritic cell line (FSDC). C. citratus infusion significantly inhibited the LPS-induced NO production and inducible NO synthase (iNOS) protein expression. All the polyphenolic fractions tested also reduced the iNOS protein levels and NO production stimulated by LPS in FSDC cells, without affecting cell viability, with the strongest effects being observed for the fractions with mono- and polymeric flavonoids (FF and TF, respectively). Our results also indicated that the anti-inflammatory properties of FF are mainly due to luteolin glycosides. In conclusion, C. citratus has NO scavenging activity and inhibits iNOS expression and should be explored for the treatment of inflammatory diseases, in particular of the gastrointestinal tract.
    Journal of medicinal food 06/2010; 13(3):681-90. · 1.39 Impact Factor
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    ABSTRACT: The management of agro-industrial residues is an important issue for environmental reasons and the reuse of byproducts represents a good alternative, especially if it is conjugated with green technologies and the production of valuable products. Portuguese elderberry pomace is rich in anthocyanins with therapeutic properties that confer to this byproduct potential to be applied in the food and pharmaceutical industries. Fractionated high pressure extractions from elderberry pomace were performed using supercritical CO2 extraction, followed by enhanced solvent extraction (ESE) with diverse CO2/ethanol/H2O solvent mixtures (0–90%, 0.5–100%, 0–95%, v/v/v), at 313K and 21MPa, in order to obtain anthocyanin-rich fractions. The ESE solvent mixtures had a substantial effect on extracts yield and composition. The maximum extraction yield (24.2%), total phenolic compounds (15.8% gallic acid equivalents), total flavonoids (8.9% epicatechin equivalents), total anthocyanins (15.0% cyanidin-3-glucoside equivalents) and antioxidant activity (IC50 of 21μg) achieved highlight the great potential of elderberry pomace for valuable applications.
    Journal of Supercritical Fluids The 01/2010; 54(2):145-152. · 2.73 Impact Factor
  • Planta Medica - PLANTA MED. 01/2010; 76(12).
  • Planta Medica - PLANTA MED. 01/2010; 76(12).
  • Planta Medica - PLANTA MED. 01/2010; 76(12).
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    ABSTRACT: Dendritic cells (DC) are professional antigen-presenting cells with a unique capacity to initiate and modulate immune responses by their ability to prime naïve T-cells. Upon stimuli, DC experience several morphologic, phenotypic and functional changes in a process referred to as maturation. This process is crucial to the biological functions of DC since their maturation status confer them the ability to polarize distinct T-cell subsets. In this work we explored the relevance of PI3-Kinase, Mitogen-Activated Protein Kinases (MAPKs) and NF-kappaB on cytokines/chemokines and co-stimulatory molecules expression. As experimental model, we used a fetal skin-derived dendritic cell line (FSDC) induced to mature by treatment with lipopolysaccharide (LPS). Morphology and ultrastructure were analyzed by confocal and electron microscopies, respectively. Levels of phosphorylated proteins were evaluated by Western blot, production of cytokines/chemokines was analyzed by protein arrays and the expression of surface molecules was evaluated by flow cytometry. The effect of specific inhibitors of the studied signaling pathways on the transcription of cytokines/chemokines and co-stimulatory molecules was accessed by Quantitative Real-Time RT-PCR. The results showed that LPS induces significant morphological and ultrastructural changes in FSDC. Western blot analysis revealed that LPS challenge promotes an early and transient activation of NF-kappaB, ERK1/2, p38 MAPK, along with a more sustained PI3 kinase/AKT activation. The co-stimulatory CD40, CD80, CD86 and antigen-presenting MHC class I and II molecules were increased and among secreted molecules, interleukin IL-6, CCL5, G-CSF, CCL2, CXCL2 were strongly up-regulated. Using a pharmacological approach we observed that LPS-induced increase of these molecules was differentially regulated by the distinct signaling pathways. Moreover, the polarizing T(h)2 cytokines/chemokines induced by LPS in FSDC were found to be positively regulated by NF-kappaB and ERK and negatively modulated by p38 MAPK. Altogether these results suggest that the use of pharmacological inhibitors to manipulate DC maturation, namely the polarizing T(h)1/T(h)2 cytokine/chemokine profile, may be useful in the development of more specific immunotherapeutic protocols.
    Molecular Immunology 07/2009; 46(13):2481-92. · 2.65 Impact Factor
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    ABSTRACT: Dendritic cells (DC) are major players in initiating immune responses by activating T-lymphocytes. They act as sentinels in peripheral tissues, continuously scavenging for antigens in their immediate surroundings. Their involvement in T-cell responses consists of a linear progression of events starting with capture of antigens in peripheral tissues, such as the skin, followed by migration to draining lymphoid organs and presentation of antigen-derived peptides to induce T-cell priming. In the last years, a number of DC lines have been generated and the electron microscopy has been used to define their characteristics, thus contributing to their formal validation. A cell line with features of early DC precursors was previously established from fetal mouse skin (FSDC), but its ultrastructural organization was not fully investigated. Here we report such investigation using light (LM), scanning electron (SEM) and transmission electron microscopy (TEM). The goal is to use FSDC as a model system to evaluate the safety and effectiveness of selected plant extracts, fractions and isolated polyphenols against inflammatory processes. Our preliminary results with these cells showed anti-inflammatory activity for some of the extracts we are currently investigating.
    Microscopy and Microanalysis 01/2009; 15. · 2.50 Impact Factor
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    ABSTRACT: The main purpose of this study was the characterisation of 'Serra da Lousã' heather honey by using novel statistical methodology, relevant principal component analysis, in order to assess the correlations between production year, locality and composition. Herein, we also report its chemical composition in terms of sugars, glycerol and ethanol, and physicochemical parameters. Sugars profiles from 'Serra da Lousã' heather and 'Terra Quente de Trás-os-Montes' lavender honeys were compared and allowed the discrimination: 'Serra da Lousã' honeys do not contain sucrose, generally exhibit lower contents of turanose, trehalose and maltose and higher contents of fructose and glucose. Different localities from 'Serra da Lousã' provided groups of samples with high and low glycerol contents. Glycerol and ethanol contents were revealed to be independent of the sugars profiles. These data and statistical models can be very useful in the comparison and detection of adulterations during the quality control analysis of 'Serra da Lousã' honey.
    Natural product research 02/2008; 22(17):1560-82. · 1.01 Impact Factor