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      Polyphenol-Rich Extract of Syzygium cumini Leaf Dually Improves Peripheral Insulin Sensitivity and Pancreatic Islet Function in Monosodium L-Glutamate-Induced Obese Rats

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          Abstract

          Syzygium cumini (L.) Skeels (Myrtaceae) has been traditionally used to treat a number of illnesses. Ethnopharmacological studies have particularly addressed antidiabetic and metabolic-related effects of extracts prepared from its different parts, especially seed, and pulp-fruit, however. there is a lack of studies on phytochemical profile and biological properties of its leaf. As there is considerable interest in bioactive compounds to treat metabolic syndrome and its clustered risk factors, we sought to characterize the metabolic effects of hydroethanolic extract of S. cumini leaf (HESc) on lean and monosodium L-glutamate (MSG)-induced obese rats. HPLC-MS/MS characterization of the HESc polyphenolic profile, at 254 nm, identified 15 compounds pertaining to hydrolysable tannin and flavanol subclasses. At 60 days of age, both groups were randomly assigned to receive HESc (500 mg/kg) or vehicle for 30 days. At the end of treatment, obese+HESc exhibited significantly lower body weight gain, body mass index, and white adipose tissue mass, compared to obese rats receiving vehicle. Obese rats treated with HESc showed a twofold increase in lipolytic activity in the periepididymal fat pad, as well as, brought triglyceride levels in serum, liver and skeletal muscle back to levels close those found in lean animals. Furthermore, HESc also improved hyperinsulinemia and insulin resistance in obese+HESc rats, which resulted in partial reversal of glucose intolerance, as compared to obese rats. HESc had no effect in lean rats. Assessment of ex vivo glucose-stimulated insulin secretion showed HESc potentiated pancreatic function in islets isolated from both lean and obese rats treated with HESc. In addition, HESc (10–1000 μg/mL) increased glucose stimulated insulin secretion from both isolated rat islets and INS-1E β-cells. These data demonstrate that S. cumini leaf improved peripheral insulin sensitivity via stimulating/modulating β-cell insulin release, which was associated with improvements in metabolic outcomes in MSG-induced obese rats.

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          Identification and quantification of phenolic compounds from pomegranate (Punica granatum L.) peel, mesocarp, aril and differently produced juices by HPLC-DAD-ESI/MS(n).

          Phenolic compounds were extracted from pomegranate (Punica granatum L.) peel, mesocarp and arils. Extracts and juices were characterised by HPLC-DAD-ESI/MS(n). In total, 48 compounds were detected, among which 9 anthocyanins, 2 gallotannins, 22 ellagitannins, 2 gallagyl esters, 4 hydroxybenzoic acids, 7 hydroxycinnamic acids and 1 dihydroflavonol were identified based on their UV spectra and fragmentation patterns in collision-induced dissociation experiments. To the best of our knowledge, cyanidin-pentoside-hexoside, valoneic acid bilactone, brevifolin carboxylic acid, vanillic acid 4-glucoside and dihydrokaempferol-hexoside are reported for the first time in pomegranate fruits. Furthermore, punicalagin and pedunculagin I were isolated by preparative HPLC and used for quantification purposes. The ellagitannins were found to be the predominant phenolics in all samples investigated, among them punicalagin ranging from 11 to 20g per kilogram dry matter of mesocarp and peel as well as 4-565mg/L in the juices. The isolated compounds, extracts and juices were also assessed by the TEAC, FRAP and Folin-Ciocalteu assays revealing high correlation (R(2)=0.9995) of the TEAC and FRAP values, but also with total phenolic contents as determined by the Folin-Ciocalteu assay and by HPLC. Selection of raw materials, i.e. co-extraction of arils and peel, and pressure, respectively, markedly affected the profiles and contents of phenolics in the pomegranate juices, underlining the necessity to optimise these parameters for obtaining products with well-defined functional properties. Copyright © 2011 Elsevier Ltd. All rights reserved.
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            Glucose sensitivity and metabolism-secretion coupling studied during two-year continuous culture in INS-1E insulinoma cells.

            Rat insulinoma-derived INS-1 cells constitute a widely used beta-cell surrogate. However, due to their nonclonal nature, INS-1 cells are heterogeneous and are not stable over extended culture periods. We have isolated clonal INS-1E cells from parental INS-1 based on both their insulin content and their secretory responses to glucose. Here we describe the stable differentiated INS-1E beta-cell phenotype over 116 passages (no. 27-142) representing a 2.2-yr continuous follow-up. INS-1E cells can be safely cultured and used within passages 40-100 with average insulin contents of 2.30 +/- 0.11 microg/million cells. Glucose-induced insulin secretion was dose-related and similar to rat islet responses. Secretion saturated with a 6.2-fold increase at 15 mm glucose, showing a 50% effective concentration of 10.4 mm. Secretory responses to amino acids and sulfonylurea were similar to those of islets. Moreover, INS-1E cells retained the amplifying pathway, as judged by glucose-evoked augmentation of insulin release in a depolarized state. Regarding metabolic parameters, INS-1E cells exhibited glucose dose-dependent elevations of NAD(P)H, cytosolic Ca(2+), and mitochondrial Ca(2+) levels. In contrast, mitochondrial membrane potential, ATP levels, and cell membrane potential were all fully activated by 7.5 mm glucose. Using the perforated patch clamp technique, 7.5 and 15 mm glucose elicited electrical activity to a similar degree. A K(ATP) current was identified in whole cell voltage clamp using diazoxide and tolbutamide. As in native beta-cells, tolbutamide induced electrical activity, indicating that the K(ATP)conductance is important in setting the resting potential. Therefore, INS-1E cells represent a stable and valuable beta-cell model.
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              Brain lesions, obesity, and other disturbances in mice treated with monosodium glutamate.

              In newborn mice subcutaneous injectionis of monosodium glutamate induced acute neuronal necrosis in several regions of developing brain including the hypothanamus. As adults, treated animals showed stunted skeletal development, marked obesity, and female sterility. Pathological changes were also found in several organs associated with endocrine function. Studies of food consumption failed to demonstrate hyperphagia to explain the obesity. It is postulated that the aduls syndrome represents a multifacted nueroendocrine disturbance arising from the disruption of developing nueral centers concered in the mediation of endocrine function.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                10 March 2016
                2016
                : 7
                : 48
                Affiliations
                [1] 1Laboratory of Experimental Physiology, Department of Physiological Sciences, Federal University of Maranhão São Luís, Brazil
                [2] 2Laboratory of Endocrine Pancreas and Metabolism, Department of Estructural and Functional Biology, Institute of Biology, State University of Campinas Campinas, Brazil
                [3] 3Departments of Biochemistry, Pediatrics and Obstetrics and Gynecology, McMaster University Hamilton, ON, Canada
                [4] 4Department of Obstetrics and Gynecology, McMaster University Hamilton, ON, Canada
                [5] 5Social, Health and Technological Sciences Center, Federal University of Maranhão Imperatriz, Brazil
                Author notes

                Edited by: Adolfo Andrade-Cetto, Universidad Nacional Autónoma de México, Mexico

                Reviewed by: Marcia Hiriart, Universidad Nacional Autónoma de México, Mexico; Xiao Yu Tian, The Chinese University of Hong Kong, China; Alex Rafacho, Federal University of Santa Catarina, Brazil

                *Correspondence: Antonio Marcus de A. Paes, marcuspaes@ 123456ufma.br

                This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology

                Article
                10.3389/fphar.2016.00048
                4785152
                27014062
                4e478a93-665a-49a6-89e5-e46cd52de2c6
                Copyright © 2016 Sanches, França, Chagas, Gaspar, dos Santos, Gonçalves, Sloboda, Holloway, Dutra, Carneiro, Cappelli and Paes.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 10 October 2015
                : 22 February 2016
                Page count
                Figures: 7, Tables: 2, Equations: 0, References: 79, Pages: 16, Words: 0
                Funding
                Funded by: Fundação de Amparo à Pesquisa e ao Desenvolvimento Científico e Tecnológico do Maranhão 10.13039/501100003758
                Award ID: #APP01128/10; #APP00280/12
                Funded by: Conselho Nacional de Desenvolvimento Científico e Tecnológico 10.13039/501100003593
                Funded by: Canada Excellence Research Chairs, Government of Canada 10.13039/501100002784
                Categories
                Pharmacology
                Original Research

                Pharmacology & Pharmaceutical medicine
                metabolic syndrome,insulin resistance,hypertriglyceridemia,obesity,insulin secretion,jambolan,polyphenols,complementary and alternative medicine

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