Publications by authors named "Paula Andrade"

283 Publications

Biosynthetic versatility of marine-derived fungi on the delivery of novel antibacterial agents against priority pathogens.

Biomed Pharmacother 2021 Aug 26;140:111756. Epub 2021 May 26.

REQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, R. Jorge Viterbo Ferreira, nº 228, 4050-313 Porto, Portugal. Electronic address:

Despite the increasing number of novel marine natural products being reported from fungi in the last three decades, to date only the broad-spectrum cephalosporin C can be tracked back as marine fungal-derived drug. Cephalosporins were isolated in the early 1940s from a strain of Acremonium chrysogenum obtained in a sample collected in sewage water in the Sardinian coast, preliminary findings allowing the discovery of cephalosporin C. Since then, bioprospection of marine fungi has been enabling the identification of several metabolites with antibacterial effects, many of which proving to be active against multi-drug resistant strains, available data suggesting also that some might fuel the pharmaceutical firepower towards some of the bacterial pathogens classified as a priority by the World Health Organization. Considering the success of their terrestrial counterparts on the discovery and development of several antibiotics that are nowadays used in the clinical setting, marine fungi obviously come into mind as producers of new prototypes to counteract antibiotic-resistant bacteria that are no longer responding to available treatments. We mainly aim to provide a snapshot on those metabolites that are likely to proceed to advanced preclinical development, not only based on their antibacterial potency, but also considering their targets and modes of action, and activity against priority pathogens.
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http://dx.doi.org/10.1016/j.biopha.2021.111756DOI Listing
August 2021

Activation of caspase-3 in gastric adenocarcinoma AGS cells by Xylopia aethiopica (Dunal) A. Rich. fruit and characterization of its phenolic fingerprint by HPLC-DAD-ESI(Ion Trap)-MS and UPLC-ESI-QTOF-MS.

Food Res Int 2021 03 12;141:110121. Epub 2021 Jan 12.

REQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, R. Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal. Electronic address:

While the fruits of Xylopia aethiopica (Dunal) A. Rich. are important in African countries as a local trade product, their composition remains scarcely investigated. Phenolic fingerprint is herein delivered through HPLC-DAD-ESI(Ion Trap)-MS and UPLC-ESI-QTOF-MS analysis, six cinnamoylquinic acid derivatives and twenty-four flavonoid glycosides being determined, chrysoeriol-7-O-glycosides being the main constituents. A cytotoxicity screening of twenty-eight hydroethanol extracts, obtained from a collection of Guinea-Bissauan plants, against A549 and AGS carcinoma cells, revealed the selective and potent effect towards AGS cells (IC = 151 × 10 g L), upon exposure to the extract from X. aethiopica fruits. Additional experiments demonstrated insignificant effect on LDH release at 151 × 10 g L, morphological analysis further suggesting induction of apoptosis. Pro-apoptotic effects were confirmed, as the extract enabled the activation of the effector caspase-3, broadening the knowledge on the anticancer mechanisms elicited by the fruits of X. aethiopica. Phenolic constituents might contribute to the cytotoxic effects, particularly via caspase-3 activation. Considering that X. aethiopica fruit is very often referred as an anticancer ingredient in Africa, but mainly the potent cytotoxicity herein recorded, our results call for additional research aiming to identify non-phenolic constituents contributing to the effects and also to further detail the anticancer mechanisms.
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http://dx.doi.org/10.1016/j.foodres.2021.110121DOI Listing
March 2021

Trichilia catigua and Turnera diffusa extracts: In vitro inhibition of tyrosinase, antiglycation activity and effects on enzymes and pathways engaged in the neuroinflammatory process.

J Ethnopharmacol 2021 May 21;271:113865. Epub 2021 Jan 21.

REQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade Do Porto, Rua de Jorge Viterbo Ferreira, No. 228, 4050-313, Porto, Portugal. Electronic address:

Ethnopharmacological Relevance: Flavonoids interact with multiple targets in Central Nervous System resulting in a broad neuroprotection mediated by complementary processes and synergic interactions. Therefore, flavonoid-based therapies may input positive outcomes in the prevention and early management of neurodegenerative diseases. In Brazilian folk medicine Trichilia catigua is used for its neuroactive properties, such as neurostimulant, antioxidant and anti-neuroinflammatory, while Turnera diffusa is traditionally used as a tonic in neurasthenia. Both species are known to be rich in flavonoids.

Aim Of The Study: To study aqueous extracts of T. catigua and T. diffusa in terms of their antioxidant and antiglycation effects, inhibition of tyrosinase activity, and interaction with enzymes and pathways engaged in neuroinflammation. Moreover, whenever possible, to establish a relationship between the studied activities and the traditional usage of the species.

Materials And Methods: The phenolic profiles of the aqueous extracts were validated by HPLC-DAD. The effect of the extracts over mushroom tyrosinase and 5-lipoxygenase activities, as well as their capacity to impair bovine serum albumin glycation, were assessed by in vitro assays. The anti-neuroinflammatory potential of the same extracts was evaluated by their capacity to mitigate the pro-inflammatory stimulus induced in BV-2 microglia cells by interferon-gamma.

Results: T. catigua extract, a rich mixture of phenolic acids, catechins and flavonolignans, excels by its ability to decrease lipid peroxidation (EC = 227.18 ± 9.04 μg/mL), and to work as anti-glycation agent, and inhibitor of both tyrosinase and 5-lipoxigenase (IC = 358.84 ± 19.05 and 56.25 ± 14.53 μg/mL, respectively). However, only T. diffusa extract, mainly composed by luteolin derivatives, is able to lower NO production by BV-2 microglia cells stimulated with interferon-gamma, despite its lower activities in the other assays.

Conclusions: Overall, this work highlights the value of medicinal plant extracts as sources of bioactive flavonoid-rich extracts with neuroactive effects. Furthermore, these results support their application as alternative strategies to develop functional foods and therapeutics to fight chronic neurodegenerative disorders.
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http://dx.doi.org/10.1016/j.jep.2021.113865DOI Listing
May 2021

Cassia sieberiana DC. leaves modulate LPS-induced inflammatory response in THP-1 cells and inhibit eicosanoid-metabolizing enzymes.

J Ethnopharmacol 2021 Apr 24;269:113746. Epub 2020 Dec 24.

REQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, R. Jorge Viterbo Ferreira, nº 228, 4050-313, Porto, Portugal. Electronic address:

Ethnopharmacological Relevance: According to ethnobotanical surveys, Cassia sieberiana DC. (1825) is a particularly reputed species in African folk Medicine, namely due to the application of its leaves and roots for the treatment of diseases and symptomatology that appear to be related with an inflammatory background. In contrast with the roots of the plant, the leaves remain to be investigated, which prompted us to further detail mechanisms underlying their anti-inflammatory properties, by using in vitro models of disease.

Aim Of The Study: Considering its use in the amelioration and treatment of conditions that frequently underlie an inflammatory response, C. sieberiana leaves extract was prioritized amongst a collection of extracts obtained from plants collected in Guinea-Bissau. As such, this work aims to deliver experimental data on the anti-inflammatory properties of C. sieberiana leaf and to establish possible associations with its chemical composition, thus providing a rationale on its use in folk Medicine.

Materials And Methods: The chemical profile of an hydroethanol extract obtained from the leaves of the plant was established by HPLC-DAD-ESI/MS in order to identify bioactives. The extract and its main compound were tested towards a series of inflammatory mediators, both in enzymatic and cell-based models. The capacity to interfere with the eicosanoid-metabolizing enzymes 5-lipoxygenase (5-LOX), cyclooxygenase-1 (COX-1) and -2 (COX-2) was evaluated in cell-free systems, while the effects in interleukin 6 (IL-6) and tumour necrosis factor-α (TNF-α) levels produced by THP-1 derived macrophages were assessed through ELISA.

Results: HPLC-DAD-ESI/MS analysis of the extract elucidated a chemical profile qualitatively characterized by a series of anthraquinones, particularly rhein derivatives, and nine flavonols, most of which 3-O-glycosylated. Considering the concentrations of the identified compounds, quercetin was detached as the main component. Effects of the hydroethanol extract obtained from C. sieberiana leaves against key enzymes of the arachidonic acid cascade were recorded, namely a concentration-dependent inhibition against 5-LOX, at concentrations ranging from 16 to 250 μg mL and a selective inhibitory action upon COX-2 (IC = 3.58 μg mL) in comparison with the isoform COX-1 (IC = 9.10 μg mL). Impact on inflammatory cytokines was also noted, C. sieberiana leaf extract significantly decreasing IL-6 levels in THP-1 derived macrophages at 250 and 500 μg mL. In contrast, TNF-α levels were found to be increased in the same model. Quercetin appears to partially account for the observed effects, namely due to the significant inhibitory effects on the activity of the arachidonic acid metabolizing enzymes COX-2 and 5-LOX.

Conclusions: The anti-inflammatory effects herein reported provide a rationale for the use of C. sieberiana leaves in African folk practices, such as in the treatment of arthritis, rheumatism and body aches. Considering the occurrence of flavonoidic and anthraquinonic constituents, as well as the observed anti-inflammatory properties of quercetin, recorded effects must be related with the presence of several bioactives.
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http://dx.doi.org/10.1016/j.jep.2020.113746DOI Listing
April 2021

Polyphenols from Brown Seaweeds (Ochrophyta, Phaeophyceae): Phlorotannins in the Pursuit of Natural Alternatives to Tackle Neurodegeneration.

Mar Drugs 2020 Dec 18;18(12). Epub 2020 Dec 18.

REQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira n.º 228, 4050-313 Porto, Portugal.

Globally, the burden of neurodegenerative disorders continues to rise, and their multifactorial etiology has been regarded as among the most challenging medical issues. Bioprospecting for seaweed-derived multimodal acting products has earned increasing attention in the fight against neurodegenerative conditions. Phlorotannins (phloroglucinol-based polyphenols exclusively produced by brown seaweeds) are amongst the most promising nature-sourced compounds in terms of functionality, and though research on their neuroprotective properties is still in its infancy, phlorotannins have been found to modulate intricate events within the neuronal network. This review comprehensively covers the available literature on the neuroprotective potential of both isolated phlorotannins and phlorotannin-rich extracts/fractions, highlighting the main key findings and pointing to some potential directions for neuro research ramp-up processes on these marine-derived products.
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http://dx.doi.org/10.3390/md18120654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766193PMC
December 2020

Gustavia gracillima Miers. flowers effects on enzymatic targets underlying metabolic disorders and characterization of its polyphenolic content by HPLC-DAD-ESI/MS.

Food Res Int 2020 11 16;137:109694. Epub 2020 Sep 16.

REQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, R. Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal. Electronic address:

Notwithstanding Gustavia gracillima Miers widespread distribution in neotropical regions, its chemical profile and biological properties remain uninvestigated. A methanol extract obtained from the flowers was characterized through HPLC-DAD-ESI/MS, nine ellagic acid derivatives and twelve kaempferol 3-O-glycosides being identified and quantitated for the first time at the species and genus. Preliminary cytotoxicity screening did not reveal noticeable effects upon gastrointestinal representative cell lines (AGS, Caco-2 and Hep G2), which further prompted us to evaluate the impact in a series of targets involved in metabolic disorders and associated complications. Despite of the moderate inhibition towards 5-lipoxygense activity, G. gracillima methanol extract displayed significant effects on carbohydrates-hydrolysing enzymes. In contrast with the antidiabetic reference drug acarbose, the extract was able to selectively inhibit yeast α-glucosidase activity (IC = 4.72 µg/mL), with negligible inhibitory effects upon α-amylase. Kinetic studies pointed to a model of mixed inhibition with a great binding activity, characterized by an inhibitory constant of 2.91 µg/mL. The notable inhibitory activity was also confirmed in α-glucosidase homogenates isolated from human intestinal cells (IC = 34.03 µg/mL). Moreover, the extract obtained from the flowers of G. gracillima displayed significant aldose reductase inhibition (IC = 61.88 µg/mL), as well as O and NO scavenging properties. A moderate inhibitory effect was also recorded against pancreatic lipase (IC = 362.17 µg/mL) through a mixed inhibition mode. Recorded data supports the potential incorporation of G. gracillima flowers on antidiabetic herbal formulations and/or supplements, with not only straight action on carbohydrates digestion, but also direct interference with targets involved on subsequent diabetes events, such as triglycerides metabolism, inflammation and radical-mediated stress.
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http://dx.doi.org/10.1016/j.foodres.2020.109694DOI Listing
November 2020

The complexity of TB/HIV coinfection: an analysis of the social and health services context in the state of São Paulo, Brazil.

J Infect Dev Ctries 2020 10 31;14(10):1185-1190. Epub 2020 Oct 31.

Ribeirão Preto College of Nursing, Ribeirão Preto, Brazil.

Introduction: Brazil is in the 19th position of priority countries for the control of TB/HIV coinfection, so we aimed to analyze the social and health services contexts that are associated with TB/HIV coinfection in São Paulo state.

Methodology: Ecological study conducted in 645 cities of the state. The study population consisted of 10,389 new cases of TB/HIV coinfection in state residents between 2010 and 2015. The variables and indicators used in the study were collected from secondary sources. To identify the factors associated with the occurrence of TB/HIV coinfection cases, generalized additive models for location, scale and shape were used. The best distribution model was defined from the lowest Akaike information criterion value.

Results: There was an association between the occurrence of coinfection and the diagnosis of TB after death and greater treatment default. There was also an association with greater coverage of nurses and Family Health Strategy, which comprises Primary Care settings focused on families. Regarding the social context, the Gini Coefficient of inequality was identified as a determinant of coinfection.

Conclusions: The study presents the complexity of TB/HIV coinfection, proposing critical points in the health services and social context. Despite the high coverage of nurses and Family Health Strategy in some cities, this did not affect the reduction of the incidence of coinfection. These findings may be attributed to a fragmented care and focused on acute conditions. Furthermore, this model of care holds few prospects for care integration or prioritization of prevention and health promotion actions.
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http://dx.doi.org/10.3855/jidc.12241DOI Listing
October 2020

Valorisation of kitul, an overlooked food plant: Phenolic profiling of fruits and inflorescences and assessment of their effects on diabetes-related targets.

Food Chem 2021 Apr 8;342:128323. Epub 2020 Oct 8.

REQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, R. Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal. Electronic address:

Caryota urens L. has long been valued as a traditional food, the edible fruits being eaten raw and the inflorescences commonly used on sweet sap and flour production. In the current work, the phenolic profile of methanol extracts obtained from the inflorescences and fruits was unveiled for the first time, nine caffeic acid derivatives being identified and quantified. Since kitul products have been reported for their antidiabetic properties, extracts radical scavenging activity and α-amylase, α-glucosidase and aldose reductase inhibitory activity were assessed. The inflorescences' extract was particularly active against yeast α-glucosidase (IC = 1.53 μg/mL), acting through a non-competitive inhibitory mechanism. This activity was also observed in enzyme-enriched homogenates obtained from human Caco-2 cells (IC = 64.75 µg/mL). Additionally, the extract obtained from the inflorescences showed no cytotoxicity on HepG2, AGS and Caco-2 cell lines. Our data suggest that C. urens inflorescences can support the development of new functional foods with α-glucosidase inhibitory activity.
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http://dx.doi.org/10.1016/j.foodchem.2020.128323DOI Listing
April 2021

Medicinal plants utilized in Thai Traditional Medicine for diabetes treatment: Ethnobotanical surveys, scientific evidence and phytochemicals.

J Ethnopharmacol 2020 Dec 6;263:113177. Epub 2020 Aug 6.

REQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade Do Porto, R. Jorge Viterbo Ferreira, Nº 228, 4050-313, Porto, Portugal. Electronic address:

Ethnopharmacological Relevance: Diabetes mellitus remains the most lethal metabolic disease of contemporaneous times and despite the therapeutic arsenal currently available, research on new antidiabetic agents remains a priority. In recent years, the revitalization of Thai Traditional Medicine (TTM) became a clear priority for the Thai government, and many efforts have been undertaken to accelerate research on herbal medicines and their use in medical services in various hospitals. Additionally, and particularly in rural areas, treatment of diabetes and associated symptomatology frequently relies on herbal preparations recommended by practitioners of TTM. In the current work, medicinal plants used in Thailand for treating diabetes, as well as their hypoglycaemic pharmacological evidences and potential therapeutic use for diabetes-related complications were reviewed.

Materials And Methods: Ethnopharmacological information on the plant materials used in TTM for diabetes treatment was collected through literature search in a range of scientific databases using the search terms: diabetes, folk medicine, Thailand medicinal plants, traditional medicine. Information regarding scientific evidence on the antidiabetic effects of surveyed species was obtained considering not only the most common taxonomic designation, but also taxonomic synonyms, and including the keywords 'diabetes' and 'hypoglycaemic effect'.

Results: A total of 183 species known to be used for diabetes management in TTM were reviewed, with 30% of them still lacking experimental evidences to support claims regarding the mechanisms and phytochemicals underlying their antidiabetic properties. Moreover, a total of 46 bioactives displaying effective antidiabetic effects have been isolated from 24 species, their underlying mechanism(s) of action being fully or partially disclosed.

Conclusions: We deliver the most extensive survey dealing with the ethnomedicinal knowledge of Thai medicinal plants utilized on diabetes management. We are certain that the current review will spark further research on Thai plants for the development of new standardized phytomedicines through drug discovery programmes.
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http://dx.doi.org/10.1016/j.jep.2020.113177DOI Listing
December 2020

In vitro multifunctionality of phlorotannin extracts from edible Fucus species on targets underpinning neurodegeneration.

Food Chem 2020 Dec 3;333:127456. Epub 2020 Jul 3.

REQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal. Electronic address:

Bioprospecting for seaweed-derived multimodal acting products have earned increasing attention in the fight against diseases of multifactorial origin, such as neurodegenerative conditions. This is a pioneer study on the in vitro screening of neuroactive properties of phlorotannin-targeted extracts from edible Fucus species. Phlorotannin extracts exhibited multifunctional antioxidant properties, which were suggested to be responsible for counteracting glutamate toxicity in neuronal human-derived SH-SY5Y cells. They also inhibited the activity of enzymes (cholinesterases, monoaminoxidases A and B, and tyrosinase) linked to a set of events that contribute to the onset/progression of neurodegeneration. In general, the bioactivities were correlated with the total phlorotannin content and phloroglucinol tetramers were suggested to be behind the observed effects. The capacity of the phlorotannin extracts to interact with multiple in vitro targets underpinning neurodegeneration points to the potential interest of the selected seaweed species for development of new added-value products and promising neuroactive agents.
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http://dx.doi.org/10.1016/j.foodchem.2020.127456DOI Listing
December 2020

Adipogenic commitment induced by green tea polyphenols remodel adipocytes to a thermogenic phenotype.

J Nutr Biochem 2020 09 25;83:108429. Epub 2020 May 25.

Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil; Interdisciplinary Post-graduate Programme in Health Sciences, Cruzeiro do Sul University, São Paulo, Brazil.

The potential contribution of green tea (GT) to the development of thermogenic/beige cells have been scarcely investigated. Here we investigated if the beneficial effects of GT in the induction of thermogenic/beige adipocytes results from an initial cell commitment during adipogenesis. Male C57Bl/6 mice (3 months) were divided into 3 groups: Control (chow diet), Obese (cafeteria diet), and Obese + GT. Mice received GT gavage (500 mg/kg of BW) over 12 weeks (5 days/week), after 4 weeks of diet, totalizing 16 weeks of experimentation. GT treatment increased energy expenditure (EE) in mice fed with cafeteria-diet leading to reduced BW gain, decreased adiposity, reduced inflammation, and improving insulin sensitivity. Those phenotypes were associated with enhanced expression of oxidative, thermogenic and beige genes. GT induced a futile cycle through de novo lipogenesis activating the thermogenic pathway. Induction of beige phenotype occurs autonomously in adipocytes and involves the PPARγ/FGF21/AMPK/UCP1 pathway. Our study identified that metabolic changes caused by GT may involve the temporal expression of PPARγ promoting the induction of thermogenic cells by reprogramming initial steps of adipocyte commitment.
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http://dx.doi.org/10.1016/j.jnutbio.2020.108429DOI Listing
September 2020

Adding value to polyvinylpolypyrrolidone winery residue: A resource of polyphenols with neuroprotective effects and ability to modulate type 2 diabetes-relevant enzymes.

Food Chem 2020 Nov 1;329:127168. Epub 2020 Jun 1.

REQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, N° 228, 4050-313 Porto, Portugal. Electronic address:

A polyphenols-rich extract was obtained from polyvinylpolypyrrolidone (PVPP) winery residue, and its neuroprotective effects and ability to modulate the kinetics of type 2 diabetes-relevant enzymes were characterized. The PVPP-white wine extract is a mixture of polyphenols (840.08 ± 161.25 µg/mg, dry weight) dominated by proanthocyanidins and hydroxycinnamic acids, affording strong antioxidant activity, as detected by the protection of membrane lipids against oxidation and superoxide radical anion scavenging activity. Regarding type 2 diabetes framework, the extract inhibits α-glucosidase (K = 166.9 µg/mL) and aldose reductase (K = 127.5 µg/mL) through non-competitive mechanisms. Despite the modest ability to inhibit rat brain acetylcholinesterase, it protects neuronal SH-SY5Y cells against oxidative damage promoted by glutamate, decreasing reactive oxygen species generation and preserving cell redox state. Thus, PVPP-white wine extract has potential to support the development of functional foods and/or nutraceuticals aiming neuroprotection and glucose homeostasis regulation, with high relevance in Alzheimeŕs disease and type 2 diabetes interlink.
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http://dx.doi.org/10.1016/j.foodchem.2020.127168DOI Listing
November 2020

Echium plantagineum L. honey: Search of pyrrolizidine alkaloids and polyphenols, anti-inflammatory potential and cytotoxicity.

Food Chem 2020 Oct 27;328:127169. Epub 2020 May 27.

REQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira n.° 228, 4050-313 Porto, Portugal. Electronic address:

For a long time, honey has been recognized for its health-promoting properties and, consequently, has been used in traditional medicine worldwide. Apart from the beneficial bioactive compounds found in this food (e.g. polyphenols), molecules with potentially harmful effects may also be present, such as pyrrolizidine alkaloids. Aiming the quality assessment of honeys produced from Echium plantagineum L., a species known for its content in pyrrolizidine alkaloids, this work was focused in the search of these alkaloids and of polyphenols in one monofloral and two multifloral honeys, using chromatographic techniques. Additionally, their cytotoxicity and anti-inflammatory potential were assessed in cellular models. Several polyphenols were determined, but no pyrrolizidine alkaloid was detected in the analysed honey samples. Honey extracts exhibited capacity to decrease NO levels in lipopolysaccharide-stimulated murine macrophage-like cells (RAW 264.7) up to 40% at concentrations of 0.25 mg/mL. Therefore, this work highlights the health benefits of these honey samples.
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http://dx.doi.org/10.1016/j.foodchem.2020.127169DOI Listing
October 2020

Defensin 1 Eradicates Mouse Metastatic Lung Nodules from B16F10 Melanoma Cells.

Int J Mol Sci 2020 Apr 11;21(8). Epub 2020 Apr 11.

Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-902, Brasil.

d1 is a pea plant defensin which can be actively expressed in and shows broad antifungal activity. This activity is dependent on fungal membrane glucosylceramide (GlcCer), which is also important for its internalization, nuclear localization, and endoreduplication. Certain cancer cells present a lipid metabolism imbalance resulting in the overexpression of GlcCer in their membrane. In this work, in vitroassays using B16F10 cells showed that labeled fluorescein isothiocyanate FITC-d1 internalized into live cultured cells and targeted the nucleus, which underwent fragmentation, exhibiting approximately 60% of cells in the sub-G0/G1 stage. This phenomenon was dependent on GlcCer, and the participation of cyclin-F was suggested. In a murine lung metastatic melanoma model, intravenous injection of d1 together with B16F10 cells drastically reduced the number of nodules at concentrations above 0.5 mg/kg. Additionally, the administration of 1 mg/kg d1 decreased the number of lung inflammatory cells to near zero without weight loss, unlike animals that received melanoma cells only. It is worth noting that 1 mg/kg d1 alone did not provoke inflammation in lung tissue or weight or vital signal losses over 21 days, inferring no whole animal cytotoxicity. These results suggest that d1 could be a promising prototype for human lung anti-metastatic melanoma therapy.
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http://dx.doi.org/10.3390/ijms21082662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7219108PMC
April 2020

Vermicompost improves maize, millet and sorghum growth in iron mine tailings.

J Environ Manage 2020 Jun 31;264:110468. Epub 2020 Mar 31.

Universidade Federal de Alfenas - UNIFAL-MG, Instituto de Ciências da Natureza - ICN, Alfenas, MG, Brazil. Electronic address:

The Fundão dam was designed to store iron mine tailings in the region of Mariana, MG, Brazil. When it ruptured, the tailings overflowed. These tailings affected the soil due to the formation of a thick crust as a result of drying (compaction) and hindered the natural revegetation process. In this context, the use of organic fertilizers, including vermicompost, is method of reducing the physical limitations on root growth caused by soil properties and changing soil-metal interactions. For this reason, vermicompost was added to iron mine tailings, and its morphological and physiological effects on maize, millet and sorghum plants were studied. The experiment was conducted in a greenhouse using 6 dm pots. The plants were subjected to three treatments: mine tailings, mine tailings + vermicompost, and a reference soil. From the V3 stage onwards, biweekly growth, leaf gas exchange and chlorophyll fluorescence evaluations were performed. At the end of the experiment, dry biomass and metal, macro- and micronutrient contents were quantified, and the root morphology was evaluated. The tailings created physical limitations on root growth and had low nutrient content as well as high concentrations of chromium, iron and manganese. The addition of vermicompost favored increases in shoot and root dry biomass, increases in root length, volume, surface area and diameter, and the absorption of macro- and micronutrients, which was reflected in the growth of the studied species. In addition, vermicompost led to greater investment in thick and very thick roots, and in general, the plants showed no symptoms of metal toxicity. Considering the characteristics of the studied tailings, it can be concluded that vermicompost favors the growth of plant species and may be a viable method for beginning the recovery process in areas containing iron mine tailings.
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http://dx.doi.org/10.1016/j.jenvman.2020.110468DOI Listing
June 2020

Inhibition of Proinflammatory Enzymes and Attenuation of IL-6 in LPS-Challenged RAW 264.7 Macrophages Substantiates the Ethnomedicinal Use of the Herbal Drug Cubitt & W.W.Sm.

Int J Mol Sci 2020 Mar 31;21(7). Epub 2020 Mar 31.

REQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, R. Jorge Viterbo Ferreira, nº 228, 4050-313 Porto, Portugal.

Commonly used to treat skin injuries in Asia, several Homalium spp. have been found to promote skin regeneration and wound healing. While ethnobotanical surveys report the use of H. bhamoense trunk bark as a wound salve, there are no studies covering bioactive properties. As impaired cutaneous healing is characterized by excessive inflammation, a series of inflammatory mediators involved in wound healing were targeted with a methanol extract obtained from trunk bark. Results showed concentration-dependent inhibition of hyaluronidase and 5-lipoxygenase upon exposure to the extract, with IC values of 396.9 ± 25.7 and 29.0 ± 2.3 µg mL, respectively. trunk bark extract also exerted anti-inflammatory activity by significantly suppressing the overproduction of interleukin 6 (IL-6) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages at concentrations ranging from 125 to 1000 µg mL, while leading to a biphasic effect on nitric oxide (NO) and tumor necrosis factor alpha (TNF-α) levels. The phenolic profile was elucidated by HPLC-DAD, being characterized by the occurrence of ellagic acid as the main constituent, in addition to a series of methylated derivatives, which might underlie the observed anti-inflammatory effects. Our findings provide in vitro data on anti-inflammatory ability of trunk bark, disclosing also potential cutaneous toxicity as assessed in HaCaT keratinocytes.
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http://dx.doi.org/10.3390/ijms21072421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178040PMC
March 2020

Risk and protective factors for sudden infant death syndrome.

Rev Bras Enferm 2020 30;73(2):e20190458. Epub 2020 Mar 30.

Universidade Federal de São Paulo. São Paulo, São Paulo, Brazil.

Objectives: To verify the occurrence of the risk and protective factors for sudden infant death syndrome during nursing consultation.

Methods: Retrospective cohort study conducted based on medical records from a primary care unit in the municipality of São Paulo. The sample consisted of 63 infants assisted from January to December 2016.

Results: The average age of infants was 3.2 months. The main risk factors identified were the presence of soft objects in the crib (93.6%) and bed sharing (58.7%). Predominant protective factors were breastfeeding (95.2%) followed by updated immunization (90.5%).

Conclusions: Risk and protective factors for sudden infant death syndrome were identified in the study sample, indicating the importance of addressing the issue with families of children under 1 year of age to prevent the occurrence of such events.
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http://dx.doi.org/10.1590/0034-7167-2019-0458DOI Listing
January 2021

Evaluating the In Vitro Potential of Natural Extracts to Protect Lipids from Oxidative Damage.

Antioxidants (Basel) 2020 Mar 11;9(3). Epub 2020 Mar 11.

MARE-Marine and Environmental Sciences Centre, ESTM, Instituto Politécnico de Leiria, 2520-641 Peniche, Portugal.

Lipid peroxidation is a chemical reaction known to have negative impacts on living organisms' health and on consumer products' quality and safety. Therefore, it has been the subject of extensive scientific research concerning the possibilities to reduce it, both in vivo and in nonliving organic matrices. It can be started by a variety of oxidants, by both ROS-dependent and -independent pathways, all of them reviewed in this document. Another feature of this reaction is the capacity of lipid peroxyl radicals to react with the non-oxidized lipids, propagating the reaction even in the absence of an external trigger. Due to these specificities of lipid peroxidation, regular antioxidant strategies-although being helpful in controlling oxidative triggers-are not tailored to tackle this challenge. Thus, more suited antioxidant compounds or technologies are required and sought after by researchers, either in the fields of medicine and physiology, or in product development and biotechnology. Despite the existence of several laboratory procedures associated with the study of lipid peroxidation, a methodology to perform bioprospecting of natural products to prevent lipid peroxidation (a Lipid Peroxidation Inhibitory Potential assay, LPIP) is not yet well established. In this review, a critical look into the possibility of testing the capacity of natural products to inhibit lipid peroxidation is presented. In vitro systems used to peroxidize a lipid sample are also reviewed on the basis of lipid substrate origin, and, for each of them, procedural insights, oxidation initiation strategies, and lipid peroxidation extent monitoring are discussed.
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http://dx.doi.org/10.3390/antiox9030231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139815PMC
March 2020

New chalcone-type compounds and 2-pyrazoline derivatives: synthesis and caspase-dependent anticancer activity.

Future Med Chem 2020 03 26;12(6):493-509. Epub 2020 Feb 26.

QOPNA & LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.

There is a continuous and urgent need for new anticancer agents with novel structures and target selectivity. The anticancer activity of the prepared compounds was assessed against human lung (A549) and stomach (AGS) cancer cell lines and evaluated in the noncancer human lung fibroblast (MRC-5) cell line. 2-Pyrazolines were devoid of toxicity in all cell lines used, chalcones bearing a β-(benz)imidazole moiety being toxic toward AGS cell line. Mechanistic studies showed that these compounds trigger loss of cell viability and mitochondrial membrane potential, while eliciting morphological traits compatible with regulated cell death, which was ultimately shown to derive from caspase activation, specifically caspase-3. Chalcones have been identified as new and promising anticancer agents toward the AGS cell line.
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http://dx.doi.org/10.4155/fmc-2019-0342DOI Listing
March 2020

Endoplasmic reticulum stress signaling in cancer and neurodegenerative disorders: Tools and strategies to understand its complexity.

Pharmacol Res 2020 05 14;155:104702. Epub 2020 Feb 14.

REQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-213, Porto, Portugal. Electronic address:

The endoplasmic reticulum (ER) comprises a network of tubules and vesicles that constitutes the largest organelle of the eukaryotic cell. Being the location where most proteins are synthesized and folded, it is crucial for the upkeep of cellular homeostasis. Disturbed ER homeostasis triggers the activation of a conserved molecular machinery, termed the unfolded protein response (UPR), that comprises three major signaling branches, initiated by the protein kinase RNA-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1 (IRE1) and the activating transcription factor 6 (ATF6). Given the impact of this intricate signaling network upon an extensive list of cellular processes, including protein turnover and autophagy, ER stress is involved in the onset and progression of multiple diseases, including cancer and neurodegenerative disorders. There is, for this reason, an increasing number of publications focused on characterizing and/or modulating ER stress, which have resulted in a wide array of techniques employed to study ER-related molecular events. This review aims to sum up the essentials on the current knowledge of the molecular biology of endoplasmic reticulum stress, while highlighting the available tools used in studies of this nature.
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http://dx.doi.org/10.1016/j.phrs.2020.104702DOI Listing
May 2020

Biological Evaluation of Naproxen-Dehydrodipeptide Conjugates with Self-Hydrogelation Capacity as Dual LOX/COX Inhibitors.

Pharmaceutics 2020 Feb 3;12(2). Epub 2020 Feb 3.

REQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, R. Jorge Viterbo Ferreira, n 228, 4050-313 Porto, Portugal.

The use of peptide-drug conjugates is emerging as a powerful strategy for targeted drug delivery. Previously, we have found that peptides conjugated to a non-steroidal anti-inflammatory drug (NSAID), more specifically naproxen-dehydrodipeptide conjugates, readily form nanostructured fibrilar supramolecular hydrogels. These hydrogels were revealed as efficacious nano-carriers for drug delivery applications. Moreover, the incorporation of superparamagnetic iron oxide nanoparticles (SPIONs) rendered the hydrogels responsive to external magnetic fields, undergoing gel-to-solution phase transition upon remote magnetic excitation. Thus, magnetic dehydrodipeptide-based hydrogels may find interesting applications as responsive Magnetic Resonance Imaging (MRI) contrast agents and for magnetic hyperthermia-triggered drug-release applications. Supramolecular hydrogels where the hydrogelator molecule is endowed with intrinsic pharmacological properties can potentially fulfill a dual function in drug delivery systems as (passive) nanocariers for incorporated drugs and as active drugs themselves. In this present study, we investigated the pharmacological activities of a panel of naproxen-dehydrodipeptide conjugates, previously studied for their hydrogelation ability and as nanocarriers for drug-delivery applications. A focused library of dehydrodipeptides, containing -terminal canonical amino acids (Phe, Tyr, Trp, Ala, Asp, Lys, Met) -capped with naproxen and linked to a -terminal dehydroaminoacid (ΔPhe, ΔAbu), were evaluated for their anti-inflammatory and anti-cancer activities, as well as for their cytotoxicity to non-cancer cells, using a variety of enzymatic and cellular assays. All compounds except one were able to significantly inhibit lipoxygenase (LOX) enzyme at a similar level to naproxen. One of the compounds was able to inhibit the cyclooxygenase-2 (COX-2) to a greater extent than naproxen, without inhibiting cyclooxygenase-1 (COX-1), and therefore is a potential lead in the search for selective COX-2 inhibitors. This hydrogelator is a potential candidate for dual COX/LOX inhibition as an optimised strategy for treating inflammatory conditions.
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http://dx.doi.org/10.3390/pharmaceutics12020122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076388PMC
February 2020

Enhancement of the anti-inflammatory properties of grape pomace treated by Trametes versicolor.

Food Funct 2020 Jan;11(1):680-688

Josip Juraj Strossmayer University of Osijek, Faculty of Food Technology Osijek, Franje Kuhača 20, HR-31000 Osijek, Croatia.

The application of solid-state fermentation for the production of value-added products from the agro- and food-industry residues has been recently investigated greatly. The white-rot basidiomycete Trametes versicolor is a widely used fungi for the degradation lignocellulosic material in solid-state conditions. Grape pomace constitutes the major by-product of Vitis vinifera L. and is a source of compounds with recognized health benefits. In this study, a process for treating grape pomace with Trametes versicolor for 15 days under solid-state conditions was developed, and the phenolic profile and anti-inflammatory potential of the grape pomace extracts before and after treatment was studied. The anti-inflammatory potential of the grape pomace extracts was studied via tests based on the inhibition of 5-lipoxygenase and hyaluronidase, two key enzymes in inflammatory processes. A total of 24 phenolic compounds were identified and quantified by HPLC methods. With the exception of anthocyanins, an increase in phenolic acids, flavan-3-ols and the flavonol rutin was observed after a treatment period of 1-4 days with T. versicolor. Moreover, the increase in the phenolic content was accompanied by an enhancement in the anti-inflammatory activity of the grape pomace extracts, which was confirmed by the strong correlation between them. This is the first study providing evidence of the benefits of the application of fungal-based solid-state fermentation as an environmentally friendly process for the enhancement of the phenolic composition and anti-inflammatory potential of grape pomace, increasing the possibility of profiting from the great waste produced by the grape-processing industry.
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http://dx.doi.org/10.1039/c9fo02296aDOI Listing
January 2020

Centaurium Erythraea Extracts Exert Vascular Effects through Endothelium- and Fibroblast-dependent Pathways.

Planta Med 2020 Jan 23;86(2):121-131. Epub 2019 Oct 23.

Laboratory Bioactives Molecules, Faculty of Sciences and Techniques, University Sidi Mohamed Ben Abdellah, Fes, Morocco.

is a plant used in traditional medicine for several cardiovascular disorders, namely hypertension, but there is no scientific evidence able to provide a molecular basis for its claimed antihypertensive effects. After a preliminary screen of extracts obtained from sequential extraction of aerial parts, effects of the methanolic fraction (MFCE) on changes in perfusion pressure of isolated rat mesenteric vascular bed (MVB) and in rat cardiac fibroblasts proliferation were investigated, gathering information on the mechanisms involved in endothelium-dependent effects and their dependence on a pro-proliferative stimulus. The HPLC-DAD determination of the phenolics content of MFCE revealed the presence of 22 phenolic compounds. MFCE reduced (63.3 ± 3.9%; n = 4) perfusion pressure in MVB and almost completely abrogated the Ang II-induced increase in cardiac fibroblasts proliferation. Reduction of the perfusion pressure caused by MFCE was endothelium-dependent and occurred in parallel with an increase in NO release. These effects were inhibited by muscarinic receptor antagonists, by L-NAME (a NO synthase inhibitor), and by ODQ (a soluble guanylate cyclase inhibitor). Experiments revealed that effects required the involvement of K channels, being inhibited by tetraethylamonium (TEA; a Ca activated K channels inhibitor) and by glibenclamide (an ATP-sensitive K channels inhibitor). In conclusion, extracts from , particularly the compounds present in the MFCE, induce endothelium-dependent vasodilation and prevent fibroblast proliferation induced by angiotensin II, which can account for the claimed antihypertensive effects of in traditional medicine.
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http://dx.doi.org/10.1055/a-1023-8918DOI Listing
January 2020

Anti-inflammatory properties of Xylopia aethiopica leaves: Interference with pro-inflammatory cytokines in THP-1-derived macrophages and flavonoid profiling.

J Ethnopharmacol 2020 Feb 16;248:112312. Epub 2019 Oct 16.

REQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, R. Jorge Viterbo Ferreira, nº 228, 4050-313, Porto, Portugal. Electronic address:

Ethnopharmacological Relevance: Ethnopharmacological surveys on Guinea-Bissauan flora reveal that several species are used to treat or ameliorate the symptomatology of conditions with an inflammatory background. As such, extracts obtained from a series of plants recorded in those surveys were screened for their anti-inflammatory properties, a hydroethanolic extract obtained from the leaves of Xylopia aethiopica (Dunal) A. Rich, (Annonaceae), used on the treatment of headache, muscular pain and rheumatic pain, scoring positively and being further investigated.

Aim Of The Study: In order to identify species with anti-inflammatory properties, extracts were screened for their ability to interfere with LPS-induced TNF-α levels. Since significant effects were recorded upon treatment with the extract of the leaves obtained from X. aethiopica, further assays were conducted to elucidate additional mechanisms underlying its anti-inflammatory potential. Since little is known on the chemical composition of the plant, we also aimed to characterise its phenolic profile.

Materials And Methods: Interference with cytokines was evaluated by ELISA assay, through the quantification of TNF-α and IL-6 levels in the culture medium collected from LPS-activated THP-1-derived-macrophages. Inhibition of 5-lipoxygenase was assessed based on the oxidation of linoleic acid to 13-hydroperoxylinoleic acid. Characterization of the phenolic profile was attained by HPLC-DAD.

Results: Evaluation of TNF-α levels in LPS-challenged THP-1 macrophages evidenced a significant inhibition (>90%) upon treatment with the hydroethanolic extract obtained from X. aethiopica leaves at a concentration of 500 μg/mL. Additional anti-inflammatory effects were recorded, including a significant decrease on IL-6 levels at 250 and 500 μg/mL. The extract proved to be active towards 5-LOX, leading to significant inhibition at concentrations ranging from 16 to 250 μg/mL (IC = 85 μg/mL). Phenolic profiling allowed the identification and quantitation of eight constituents, including caffeoylquinic acids (1-3), mono-O-glycosylated flavonols (5-8), and the mono-O-glycosyl flavone luteolin-7-O-glucoside (4). The main phenolic constituent, kaempferol-3-O-rutinoside (8), was found to significantly contribute to the anti-inflammatory effects, namely through the inhibition of 5-LOX. However, no effects on the decrease of TNF-α and IL-6 levels caused by this phenolic compound were found.

Conclusion: The anti-inflammatory effects of X. aethiopica leaves are demonstrated experimentally, thus substantiating its use in folk Medicine. Relevantly, the observed anti-inflammatory properties can stimulate further studies in order to fully unveil the therapeutic potential of the plant, namely as a source of phenolic compounds with a significant ability to interfere with conventional inflammatory targets.
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http://dx.doi.org/10.1016/j.jep.2019.112312DOI Listing
February 2020

Development of a natural molluscicide prototype kit (MoluSchall) for the control of schistosomiasis mansoni transmission.

Rev Soc Bras Med Trop 2019 14;52:e20190252. Epub 2019 Oct 14.

Fundação Oswaldo Cruz, Instituto René Rachou, Pesquisa Clínica e Políticas Públicas em Doenças Infecciosas e Parasitárias, Belo Horizonte, MG, Brasil.

Introduction: In Brazil, Biomphalaria glabrata, B. tenagophila, and B. straminea are intermediate hosts of Schistosoma mansoni, the etiological agent of schistosomiasis mansoni. Molluscicide use is recommended by the WHO for controlling the transmission of this parasite. Euphorbia milii latex has shown promising results as an alternative molluscicide. Thus, a natural molluscicide prototype kit based on freeze-dried E. milii latex was developed and evaluated against Biomphalaria spp.

Methods: E. milii latex was collected, processed, and lyophilized. Two diluents were defined for freeze-dried latex rehydration, and a prototype kit, called MoluSchall, was produced. A stability test was conducted using prototype kits stored at different temperatures, and a toxicity assay was performed using Danio rerio. Additionally, MoluSchall was tested against B. glabrata under semi-natural conditions according to defined conditions in the laboratory.

Results: MoluSchall was lethal to three Brazilian snail species while exhibiting low toxicity to D. rerio. Regardless of storage temperature, MoluSchall was stable for 24 months and was effective against B. glabrata under semi-natural conditions, with the same LD100 as observed under laboratory conditions.

Conclusions: MoluSchall is a natural, effective, and inexpensive molluscicide with lower environmental toxicity than existing molluscicides. Its production offers a possible alternative strategy for controlling S. mansoni transmission.
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http://dx.doi.org/10.1590/0037-8682-0252-2019DOI Listing
October 2019

Double the Chemistry, Double the Fun: Structural Diversity and Biological Activity of Marine-Derived Diketopiperazine Dimers.

Mar Drugs 2019 Sep 27;17(10). Epub 2019 Sep 27.

REQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, R. Jorge Viterbo Ferreira, nº 228, Porto 4050-313, Portugal.

While several marine natural products bearing the 2,5-diketopiperazine ring have been reported to date, the unique chemistry of dimeric frameworks appears to remain neglected. Frequently reported from marine-derived strains of fungi, many naturally occurring diketopiperazine dimers have been shown to display a wide spectrum of pharmacological properties, particularly within the field of cancer and antimicrobial therapy. While their structures illustrate the unmatched power of marine biosynthetic machinery, often exhibiting unsymmetrical connections with rare linkage frameworks, enhanced binding ability to a variety of pharmacologically relevant receptors has been also witnessed. The existence of a bifunctional linker to anchor two substrates, resulting in a higher concentration of pharmacophores in proximity to recognition sites of several receptors involved in human diseases, portrays this group of metabolites as privileged lead structures for advanced pre-clinical and clinical studies. Despite the structural novelty of various marine diketopiperazine dimers and their relevant bioactive properties in several models of disease, to our knowledge, this attractive subclass of compounds is reviewed here for the first time.
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http://dx.doi.org/10.3390/md17100551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6835637PMC
September 2019

Combined Exercise Training Performed by Elderly Women Reduces Redox Indexes and Proinflammatory Cytokines Related to Atherogenesis.

Oxid Med Cell Longev 2019 5;2019:6469213. Epub 2019 Aug 5.

Heart Institute, Medical School Hospital, University of São Paulo, São Paulo, Brazil.

Cardiovascular benefits for the general population of combined aerobic-resistance exercise training are well-known, but the impact of this exercise training modality on the plasma lipid, inflammatory, and antioxidant status in elderly women that are exposed to a great risk of developing ischemic cardio- and cerebrovascular diseases has not been well investigated. So, we aimed to evaluate the plasma lipids, oxidative stress, and inflammatory cytokines in 27 elderly women (TRAINED group, 69.1 ± 8.1 yrs) that were performing moderate intensity combined aerobic-resistance exercise training (3 times/week for at least 18 months) and in 27 sedentary elderly women (SED group, 72.0 ± 6.4 yrs), not submitted to exercise training for at least 5 yrs. Our results showed that BMI was lower in the TRAINED group than in the SED group (25.1 ± 3.2 vs. 28.7 ± 5.1, < 0.05). The TRAINED group had lower glycemia (92 ± 3 vs. 118 ± 12, < 0.05), glycated hemoglobin (5.9 ± 0.1 vs. 6.4 ± 0.2, < 0.05), and triglycerides (98 (75-122) vs. 139 (109-214), < 0.01); equal total cholesterol (199 (175-230) vs. 194 (165-220)), LDL-cholesterol (108 (83-133) vs. 109 (98-136)), and non-HDL-cholesterol (54 (30-74) vs. 62 (26-80)); and also higher HDL-cholesterol (64 (52-77) vs. 52 (44-63), < 0.01) and LDL-C/oxLDL ratio (13378 ± 2570 vs. 11639 ± 3113, < 0.05) compared to the SED group. Proinflammatory cytokines as IL-1 (11.31 ± 2.4 vs. 28.01 ± 4.7, < 0.05), IL-6 (26.25 ± 7.4 vs. 49.41 ± 17.8, < 0.05), and TNF- (25.72 ± 2.8 vs. 51.73 ± 4.2, < 0.05) were lower in the TRAINED group than in the SED group. The TRAINED group had lower total peroxides (26.3 ± 7.4 vs. 49.0 ± 17.8, < 0.05) and oxidized LDL (1551 ± 50.33 vs. 1773 ± 74, < 0.02) and higher total antioxidant capacity (26.25 ± 7.4 vs. 49.41 ± 17.8, < 0.001) compared to the SED group. In conclusion, in TRAINED women, BMI was lower, plasma lipid profile was better, plasma oxidative stress was diminished, and there was less expression of proinflammatory interleukins than in SED, suggesting that combined aerobic-resistance exercise training may promote the protection against the complications of ischemic cardio- and cerebrovascular disease in elderly women.
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http://dx.doi.org/10.1155/2019/6469213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6701434PMC
February 2020

Phenolic Profiling and Biological Potential of Corner Leaves and Stem Bark: 5-Lipoxygenase Inhibition and Interference with NO Levels in LPS-Stimulated RAW 264.7 Macrophages.

Biomolecules 2019 08 22;9(9). Epub 2019 Aug 22.

REQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, R. Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal.

The economic value of fig trees has been globally acknowledged due to their utilization in the food industry, being also frequently used in traditional medicine. While ubiquitously distributed in Southeast Asia, Corner remains uninvestigated concerning its biological properties and chemical profile. HPLC-DAD-ESI/MS characterization of methanol extracts obtained from the stem bark and leaves allowed the identification and quantitation of 21 phenolic compounds for the first time; the stem bark was predominantly rich in flavan-3-ols and apigenin derivatives, while solely apigenin-di-glycosides have been identified and quantitated on the leaf extract. Both extracts inhibited 5-lipoxygenase (5-LOX) activity in a concentration-dependent manner, the one obtained from the stem bark being significantly more active (IC = 10.75 μg/mL). The effect of both extracts on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages was evaluated, and while the stem bark extract did not lead to a noticeable interference on nitric oxide (NO) levels, the extract obtained from the leaves notably decreased NO and L-citrulline levels at concentrations ranging from 250 to 500 μg/mL. Herein, is valorized due to its modulatory effects on inflammatory mediators and also as a source of bioactive phenols, which may fuel further studies on the development of nutraceuticals.
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http://dx.doi.org/10.3390/biom9090400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770299PMC
August 2019

Jasonia glutinosa (L.) DC., a traditional herbal medicine, reduces inflammation, oxidative stress and protects the intestinal barrier in a murine model of colitis.

Inflammopharmacology 2020 Dec 13;28(6):1717-1734. Epub 2019 Aug 13.

Departamento de Farmacología y Fisiología, Universidad de Zaragoza, Saragossa, Spain.

Jasonia glutinosa (L.) DC., known as rock tea (RT), is traditionally used in Spain as a digestive due to its beneficial properties in bowel disorders. The pharmacological nature of these properties has not been established yet. The aim of this work was to evaluate the therapeutic utility of RT in experimental colitis and to identify chemical constituents with anti-inflammatory and/or anti-oxidative properties. RT extract was prepared with ethanol in a Soxhlet apparatus and analysed by HPLC-DAD. Superoxide radical scavenging properties, xanthine oxidase and lipoxygenase (5-LOX) inhibitory activity, and capability to lower nitric oxide (NO) and tumor necrosis factor α (TNF-α) levels were measured in cell-free and cell-based assays. In the 2.5%-dextran-sodium sulphate (DSS) injury-repair model of ulcerative colitis (UC), mice were daily treated with sulfasalazine (SSZ, as reference drug, 100 mg/kg bw), RT (5, 25 and 50 mg/kg bw, p.o.), or vehicle over 20 days. Colitis was scored daily. Colon samples were examined macroscopically and histopathologically. Protein levels of myeloperoxidase (MPO), interleukins 6, and 10 (IL-6, IL-10), inducible NO synthase (iNOS), and cyclooxygenase-2 (COX-2) were studied as markers of oxidative stress and inflammatory activity. The integrity of the apical epithelial layer was assessed by immunofluorescence staining of zonula ocludens-1 (ZO-1). Finally, intestinal contractility was also evaluated by isometric myography. Fifteen phenolic compounds and three pigments were identified and quantified, of which caffeoylquinic acids, and the flavonoid, quercetin-3-O-galactoside, were the most abundant. RT extract significantly scavenged superoxide radicals, inhibited 5-LOX activity, and lowered NO and TNF-α levels. DSS-treated mice receiving RT scored clinically lower than controls during the first 3 days of DSS treatment and during the recovery period. SSZ was less effective than RT. Anatomical and histological examination of colon samples revealed that RT significantly prevented colon shortening, increased colon thickness, and lowered the macroscopic damage score. RT also significantly prevented the increase of MPO activity, IL-6 levels, iNOS and COX-2 expression, the loss of ZO-1 apical expression, and normalized contractility disturbances. In conclusion, daily administration of RT showed therapeutic properties in the DSS-model of UC. The benefits of RT can likely be attributed to its anti-inflammatory and antioxidant phenolic and flavonoid constituents.
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http://dx.doi.org/10.1007/s10787-019-00626-0DOI Listing
December 2020

Extraction of phospholipid-rich fractions from egg yolk and development of liposomes entrapping a dietary polyphenol with neuroactive potential.

Food Chem Toxicol 2019 Nov 1;133:110749. Epub 2019 Aug 1.

REQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, no. 228, 4050-313, Porto, Portugal. Electronic address:

A new protocol to obtain egg yolk phospholipids in ethanol is presented. Rutin-phospholipids nanoliposomes were prepared and characterized. The procedure takes advantage of the different solubility of egg yolk lipids in ethanol and acetone at low temperature, to efficiently obtain a phospholipid-rich fraction of high purity degree. The phospholipid content in the final fraction is 208.65 ± 26.46 μmol/g fresh egg yolk (16%), accounting for ca. 96% of the extract's dry weight. The phospholipid-rich fraction contains cholesterol (0.069-0.082 cholesterol/phospholipid molar ratio), and vestigial amounts of lutein and zeaxanthin (89.24 ± 9.76 and 14.9 ± 2.16 ng/g of fresh egg yolk, respectively). Saturated fatty acids dominate the extracted phospholipids (50% of egg's total yolk phospholipids), the levels of monounsaturated ranging from 20 to 25%, and polyunsaturated up to 35%. Rutin-liposomes, prepared with phospholipid-rich fraction, presented mean diameter <140 nm, negative surface charge (Zeta potential ~ -13 mV), and entrapment efficiency of rutin up to 87%. In human neuroblastoma cell line SH-SY5Y, rutin-liposomes (lipid 25 μM + rutin 16.7 μM) attenuated glutamate-induced cytotoxicity, in part by reducing the formation of intracellular reactive species, pointing to their potential application as new functional neuroprotective agents.
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http://dx.doi.org/10.1016/j.fct.2019.110749DOI Listing
November 2019
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