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      Antioxidant, antihyperglycemic, and antidiabetic activity of Apis mellifera bee tea

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          Abstract

          Diabetes has emerged as one of the largest global epidemics; it is estimated that by 2035, there will be 592 million diabetic people in the world. Brazilian biodiversity and the knowledge of traditional peoples have contributed to the treatment of several diseases, including diabetes. Apis mellifera bee tea is used by indigenous Brazilians to treat diabetes, and this traditional knowledge needs to be recorded and studied.The objective of this study was to record the use and to evaluate the antioxidant, antihyperglycemic, and antidiabetic activity of Apis mellifera bee tea, which is used by the Guarani and Kaiowá indigenous people for the treatment of diabetes. Semi-structured interviews were performed with Guarani and Kaiowá ethnic indigenous people from the State of Mato Grosso do Sul, Brazil, seeking to identify the animal species used for medicinal purposes. For the experimental procedures, tea prepared with macerated Apis mellifera bees was used. In vitro assays were performed to evaluate antioxidant activity; direct free radical scavenging, protection against oxidative hemolysis, lipid peroxidation were evaluated in human erythrocytes and potential in inhibiting the formation of advanced glycation end products (AGEs). In vivo, normoglycemic Swiss male mice treated with Apis mellifera tea (AmT) were subjected to the oral glucose tolerance test and compared with control and metformin-treated groups. Diet-induced diabetic mice were treated for 21 days with AmT and evaluated for glycemia and malondialdehyde levels in the blood, liver, nervous system, and eyes. During interviews, the indigenous people described the use of Apis mellifera bee tea for the treatment of diabetes. In in vitro assays, AmT showed direct antioxidant activity and reduced oxidative hemolysis and malondialdehyde generation in human erythrocytes. The AmT inhibited the formation of AGEs by albumin-fructose pathways and methylglyoxal products. In vivo, after oral glucose overload, normoglycemic mice treated with AmT had reduced hyperglycemia at all times evaluated up to 180 min. AmT also reduced hyperglycemia and malondialdehyde levels in the blood, liver, nervous system, and eyes of diabetic mice to similar levels as those in metformin-treated mice and normoglycemic controls. In summary, Apis mellifera bee tea showed antioxidant, antihyperglycemic, and antidiabetic activity, which provides support for the therapeutic application of Guarani and Kaiowá indigenous knowledge.

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          Oxidative damage in multiple sclerosis lesions

          Multiple sclerosis is a chronic inflammatory disease of the central nervous system, associated with demyelination and neurodegeneration. The mechanisms of tissue injury are currently poorly understood, but recent data suggest that mitochondrial injury may play an important role in this process. Since mitochondrial injury can be triggered by reactive oxygen and nitric oxide species, we analysed by immunocytochemistry the presence and cellular location of oxidized lipids and oxidized DNA in lesions and in normal-appearing white matter of 30 patients with multiple sclerosis and 24 control patients without neurological disease or brain lesions. As reported before in biochemical studies, oxidized lipids and DNA were highly enriched in active multiple sclerosis plaques, predominantly in areas that are defined as initial or ‘prephagocytic’ lesions. Oxidized DNA was mainly seen in oligodendrocyte nuclei, which in part showed signs of apoptosis. In addition, a small number of reactive astrocytes revealed nuclear expression of 8-hydroxy-d-guanosine. Similarly, lipid peroxidation-derived structures (malondialdehyde and oxidized phospholipid epitopes) were seen in the cytoplasm of oligodendrocytes and some astrocytes. In addition, oxidized phospholipids were massively accumulated in a fraction of axonal spheroids with disturbed fast axonal transport as well as in neurons within grey matter lesions. Neurons stained for oxidized phospholipids frequently revealed signs of degeneration with fragmentation of their dendritic processes. The extent of lipid and DNA oxidation correlated significantly with inflammation, determined by the number of CD3 positive T cells and human leucocyte antigen-D expressing macrophages and microglia in the lesions. Our data suggest profound oxidative injury of oligodendrocytes and neurons to be associated with active demyelination and axonal or neuronal injury in multiple sclerosis.
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            Propolis: is there a potential for the development of new drugs?

            Propolis has plenty of biological and pharmacological properties and its mechanisms of action have been widely investigated in the last years, using different experimental models in vitro and in vivo. Researchers have been interested in the investigation of isolated compounds responsible for propolis action; however, there is lack of clinical research on the effects of propolis. Since propolis-containing products have been marketed and humans have used propolis for different purposes, the goal of this review is to discuss the potential of propolis for the development of new drugs, by comparing data from the literature that suggest candidate areas for the establishment of drugs against tumors, infections, allergy, diabetes, ulcers and with immunomodulatory action. The efficacy of propolis in different protocols in vitro and in vivo suggests its therapeutic properties, but before establishing a strategy using this bee product, it is necessary to study: (a) the chemical nature of the propolis sample. (b) Propolis efficacy should be compared to well-established parameters, e.g. positive or negative controls in the experiments. Moreover, possible interactions between propolis and other medicines should be investigated in humans as well. (c) Clinical investigation is needed to evaluate propolis potential in patients or healthy individuals, to understand under which conditions propolis may promote health. Data point out the importance of this research field not only for the readers and researchers in the scientific community waiting for further clarification on the potential of propolis but also for the pharmaceutical industry that looks for new drugs. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
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              5' AMP-activated protein kinase activation causes GLUT4 translocation in skeletal muscle.

              It has previously been reported that exercise causes an increase in glucose uptake in skeletal muscle and also an increase in 5' AMP-activated protein kinase (AMPK) activity. 5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICA-riboside), an analog of adenosine, is taken up into cells and phosphorylated to form AICA-riboside monophosphate (ZMP), which can also activate AMPK. This study was designed to determine whether the increase in glucose uptake observed with AMPK activation by AICA-riboside is due to GLUT4 translocation from an intracellular location to the plasma membranes, similar to that seen in response to contraction. Rat hindlimbs were perfused with Krebs-Henseleit bicarbonate containing 4% bovine serum albumin, washed bovine erythrocytes, 8 mmol/l glucose, and +/-2 mmol/AICA-riboside or +/-60 nmol/l insulin. Perfusion medium containing AICA-riboside was found to significantly increase AMPK activity, glucose uptake, and GLUT4 translocation in skeletal muscle above basal levels. Insulin-perfused muscles showed significant increases in glucose uptake and GLUT4 translocation, but AMPK activation was not significantly changed from basal levels. These results provide evidence that the increased glucose uptake observed with AMPK activation by AICA-riboside in perfused rat hindlimb muscles is due to an increase in the translocation of GLUT4 to surface membranes.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: Methodology
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Validation
                Role: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: ValidationRole: Writing – original draft
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: ValidationRole: Writing – original draft
                Role: Formal analysisRole: InvestigationRole: Methodology
                Role: Formal analysisRole: InvestigationRole: Methodology
                Role: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: ValidationRole: Visualization
                Role: Formal analysisRole: Funding acquisitionRole: InvestigationRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                5 June 2018
                2018
                : 13
                : 6
                : e0197071
                Affiliations
                [1 ] Binational Campus Oiapoque, Federal University of Amapá—UNIFAP, Amapá, Brazil
                [2 ] Research Group on Biotechnology and Bioprospecting Applied to Metabolism, Federal University of Grande Dourados–UFGD, Dourados, Brazil
                [3 ] School of Environmental and Biological Science, Federal University of Grande Dourados–UFGD, Dourados, Brazil
                [4 ] Laboratory of Cardiovascular Reactivity–LRC, Nucleus of Metabolic Syndrome, Biological Sciences and Health Institute—ICBS, Federal University of Alagoas–UFAL, Alagoas, Brazil
                [5 ] Faculty of Pharmaceutical Sciences, Federal University of Amazonas, Manaus, Brazil
                [6 ] Laboratory of Natural Products am Mass Spectrometry, Federal University of Mato Grosso do Sul–UFMS, Mato Grosso do Sul, Brazil
                Stellenbosch University, SOUTH AFRICA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0003-0253-8907
                http://orcid.org/0000-0001-5764-2125
                Article
                PONE-D-17-32027
                10.1371/journal.pone.0197071
                5988306
                29870561
                4b8b907c-b8e5-4616-9322-105416fabe9d
                © 2018 Melo da Cunha et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 31 August 2017
                : 25 April 2018
                Page count
                Figures: 5, Tables: 3, Pages: 17
                Funding
                Funded by: Development of Education, Science and Technology of Mato Grosso do Sul - FUNDECT
                Funded by: National Council for Scientific and Technological Development - CNPq
                Funded by: Brazilian Federal Agency for the Support and Evaluation of Graduate Education - CAPES
                This work was supported by grants from Foundation to Support to Fundação de Apoio ao Desenvolvimento do Ensino, Ciência e Tecnologia do Estado de Mato Grosso do Sul (FUNDECT) - http://fundect.ledes.net/; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) - http://www.capes.gov.br/; Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) – http://www.cnpq.br/; and Funding announcement FUNDECT/CAPES no. 27/2015 – PAPOS FASE II. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Endocrinology
                Endocrine Disorders
                Diabetes Mellitus
                Medicine and Health Sciences
                Metabolic Disorders
                Diabetes Mellitus
                Biology and Life Sciences
                Organisms
                Eukaryota
                Animals
                Invertebrates
                Arthropoda
                Insects
                Hymenoptera
                Bees
                Honey Bees
                Biology and Life Sciences
                Biochemistry
                Antioxidants
                Biology and Life Sciences
                Nutrition
                Diet
                Beverages
                Tea
                Medicine and Health Sciences
                Nutrition
                Diet
                Beverages
                Tea
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Blood Cells
                Red Blood Cells
                Physical sciences
                Chemistry
                Chemical compounds
                Organic compounds
                Vitamins
                Vitamin C
                Physical sciences
                Chemistry
                Organic chemistry
                Organic compounds
                Vitamins
                Vitamin C
                Biology and Life Sciences
                Biochemistry
                Proteins
                Post-Translational Modification
                Glycation
                Medicine and Health Sciences
                Metabolic Disorders
                Hyperglycemia
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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