3 results on '"Đorđević, Miloš"'
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2. Centaurium erythraea methanol extract protects red blood cells from oxidative damage in streptozotocin-induced diabetic rats.
- Author
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Đorđević, Miloš, Mihailović, Mirjana, Arambašić Jovanović, Jelena, Grdović, Nevena, Uskoković, Aleksandra, Tolić, Anja, Sinadinović, Marija, Rajić, Jovana, Mišić, Danijela, Šiler, Branislav, Poznanović, Goran, Vidaković, Melita, and Dinić, Svetlana
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BLOOD sugar analysis , *DIABETES prevention , *PROTEIN analysis , *ENZYME metabolism , *ERYTHROCYTE metabolism , *ERYTHROCYTES , *ALTERNATIVE medicine , *ANIMAL experimentation , *CHOLESTEROL , *DIABETES , *GLUTATHIONE , *GLYCOSYLATED hemoglobin , *GLYCOSYLATION , *HYPOGLYCEMIC agents , *INSULIN , *MEDICINAL plants , *LIPID peroxidation (Biology) , *ORAL drug administration , *OXIDOREDUCTASES , *RATS , *SUPEROXIDE dismutase , *PLANT extracts , *OXIDATIVE stress , *PLANT anatomy , *IN vivo studies - Abstract
Ethnopharmacological relevance Centaurium erythraea Rafn (CE) is a traditional medicinal herb in Serbia with antidiabetic, digestive, antipyretic and antiflatulent effects Aim of the study To investigate the potential protective effects of the methanol extract of the aerial parts of CE against glyco-oxidative stress in red blood cells (RBCs) in rats with experimentally induced diabetes. Material and methods Diabetes was induced in Wistar rats by intraperitoneal (i.p.) injection of multiple low-dose streptozotocin (STZ) (40 mg/kg, for five consecutive days), with the 1st day after the last STZ injection taken as the day of diabetes onset. The methanol extract of CE (100 mg/kg) was administered orally and daily, two weeks before the first STZ injection, during the 5-day treatment with STZ, and for four weeks after the STZ injections (pre-treated group) or for four weeks after diabetes onset (post-treated group). The effect of CE extract administration on the redox status of RBCs was evaluated by assessing lipid peroxidation, the ratio of reduced/oxidized glutathione (GSH/GSSG), the level of S-glutathionylated proteins (GSSP) and the enzymatic activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) in RBCs four weeks after diabetes onset. The major biochemical parameters of diabetes, protein glycation/glycosylation of erythrocytes and parameters which correlate with their aggregation and deformability were also evaluated. Results Daily application of CE extract to STZ-induced diabetic rats provided important antidiabetic effects, observed in both pre-treated and post-treated groups of diabetic rats as elevated serum insulin concentration, reduction of blood glucose and glycated hemoglobin concentrations and an improved lipid profile. Antioxidant effects of CE extract were detected in RBCs of diabetic rats and observed as decreased lipid peroxidation and ameliorated oxidative damage as a result of increased SOD, CAT and GR activities, an improved GSH/GSSG ratio and reduced GSSP levels. Moreover, the CE extract protected RBC proteins from hyperglycemia-induced damage by reducing non-enzymatic glycation and enzymatic glycosylation processes. CE extract was more effective when applied before diabetes induction (pre-treated group). Conclusions The results of this study show that the Centaurium erythraea methanol extract protects RBCs in diabetic animals from oxidative damage. They provide additional support for the application of this traditionally used plant in diabetes management. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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3. Centaurium erythraea extract improves survival and functionality of pancreatic beta-cells in diabetes through multiple routes of action.
- Author
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Đorđević, Miloš, Grdović, Nevena, Mihailović, Mirjana, Arambašić Jovanović, Jelena, Uskoković, Aleksandra, Rajić, Jovana, Sinadinović, Marija, Tolić, Anja, Mišić, Danijela, Šiler, Branislav, Poznanović, Goran, Vidaković, Melita, and Dinić, Svetlana
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DRUG administration routes , *IMMUNOCHEMISTRY , *ANIMAL experimentation , *CELL physiology , *DIABETES , *ANTINEOPLASTIC agents , *CELL survival , *TREATMENT effectiveness , *RATS , *OXIDATIVE stress , *HISTOLOGICAL techniques , *CELL proliferation , *PANCREATIC beta cells , *LIPID peroxidation (Biology) ,THERAPEUTIC use of plant extracts - Abstract
Centaurium erythraea Rafn (CE) is used as a traditional medicinal plant in Serbia to treat different ailments due to its antidiabetic, antipyretic, antiflatulent and detoxification effects. Elucidation of the mechanisms that underlie the antioxidant and pro-survival effects of the CE extract (CEE) in beta-cells and pancreatic islets from streptozotocin (STZ)-treated diabetic rats. Diabetes was induced in rats by multiple applications of low doses of STZ (40 mg/kg intraperitoneally (i.p.), for five consecutive days). CEE (100 mg/kg) was administered orally, in the pre-treated group for two weeks before diabetes induction, during the treatments with STZ and for four weeks after diabetes onset, and in the post-treatment group for four weeks after diabetes induction. The impact of CEE on diabetic islets was estimated by histological and immunohistochemical examination of the pancreas. Molecular mechanisms of the effects of CEE were also analyzed in insulinoma Rin-5F cells treated with STZ (12 mM) and CEE (0.25 mg/mL). Oxidative stress was evaluated by assessing the levels of DNA damage, lipid peroxidation, protein S-glutathionylation and enzymatic activities and expression of CAT, MnSOD, CuZnSOD, GPx and GR in beta-cells. The presence and activities of the redox-sensitive and islet-enriched regulatory proteins were also analyzed. Treatment with CEE ameliorated the insulin level and glycemic control in STZ-induced diabetic rats by improving the structural and functional properties of pancreatic islets through multiple routes of action. The disturbance of islet morphology and islet cell contents in diabetes was reduced by the CEE treatment and was associated with a protective effect of CEE on the levels of insulin, GLUT-2 and p-Akt in diabetic islets. The antioxidant effect of CEE on STZ-treated beta-cells was displayed as reduced DNA damage, lipid peroxidation, protein S-glutathionylation and alleviation of STZ-induced disruption in MnSOD, CuZnSOD and CAT enzyme activities. The oxidative stress-induced disturbance of the transcriptional regulation of CAT, MnSOD, CuZnSOD, GPx and GR enzymes in beta-cells was improved after the CEE treatment, and was observed as readjustment of the presence and activities of redox-sensitive NFκB-p65, FOXO3A, Sp1 and Nrf-2 transcription factors. The observed CEE-mediated induction of proliferative and pro-survival pathways and insulin expression/secretion after STZ-induced oxidative stress in beta-cells could be partially attributed to a fine-tuned modulation of the activities of pro-survival Akt, ERK and p38 kinases and islet-enriched Pdx-1 and MafA regulatory factors. The results of this study provide evidence that CEE improves the structural and functional properties of pancreatic beta-cells by correcting the endogenous antioxidant regulatory mechanisms and by promoting proliferative and pro-survival pathways in beta-cells. Image 1 [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
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