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Antidiabetic Effects of the Ethanolic Root Extract of Uvaria chamae P. Beauv (Annonaceae) in Alloxan-Induced Diabetic Rats: A Potential Alternative Treatment for Diabetes Mellitus.

ABSTRACT: Diabetes mellitus has been a menace to mankind from time immemorial. However, a natural product such as U. chamae P. Beauv (Annonaceae) offers alternative treatment for diabetes mellitus. The study aimed at evaluating antidiabetic activity of the ethanolic root extract of U. chamae in alloxan-induced diabetic rats. Diabetes was induced in Sprague Dawley rats after overnight fast with 150?mg/kg alloxan intraperitoneally. After 72?h, those with plasma glucose levels >200?mg/dl were classified as diabetic. Five diabetic rats in each group were treated daily for 14?days orally with 100, 250, and 400?mg/kg of the extract, glibenclamide (71?µg/kg) and pioglitazone (429?µg/kg), respectively, while another group was untreated. Control received 0.5?ml of Acacia senegal. Effects of extract on glucose, other biochemical, and hematological parameters were evaluated. ?-amylase and ?-glucosidase inhibitory activities of extract and its fractions were also evaluated. Percentage inhibition and IC₅₀ values were determined. Diabetic control was achieved on the 7th day of the study with 100, 250, and 400?mg/kg of the extract showing glucose reduction of 72.14%, 78.75%, and 87.71%, respectively. The HDL-cholesterol levels of diabetic rats treated with extracts were significantly increased. Extract and its fractions caused ?-amylase and ?-glucosidase inhibition. Histologically, pancreas of diabetic rats treated with extract showed regenerated islet cells which were not seen in rats treated with glibenclamide and pioglitazone. This study showed that U. chamae has antidiabetic activity which may be through ?-amylase and ?-glucosidase inhibition and regeneration of pancreatic beta cells. Also, it may reduce the risk of cardiovascular disease by increasing HDL-cholesterol levels.

SUBMITTER: Emordi JE

PROVIDER: S-EPMC6250042 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Antidiabetic Effects of the Ethanolic Root Extract of Uvaria chamae P. Beauv (Annonaceae) in Alloxan-Induced Diabetic Rats: A Potential Alternative Treatment for Diabetes Mellitus.

Emordi Jonathan Emeka JE Agbaje Esther Oluwatoyin EO Oreagba Ibrahim Adekunle IA Iribhogbe Osede Ignis OI

Advances in pharmacological sciences 20181108

Diabetes mellitus has been a menace to mankind from time immemorial. However, a natural product such as U. chamae P. Beauv (Annonaceae) offers alternative treatment for diabetes mellitus. The study aimed at evaluating antidiabetic activity of the ethanolic root extract of U. chamae in alloxan-induced diabetic rats. Diabetes was induced in Sprague Dawley rats after overnight fast with 150 mg/kg alloxan intraperitoneally. After 72 h, those with plasma glucose levels >200 mg/dl were c ...[more]

PMID: 30532775

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Project description:Zanthoxylum rhetsa (ZR) is used traditionally to manage a variety of ailments, including diabetes. Oxidative stress may accelerate the diabetic condition. The available antidiabetic and antioxidant drugs have many shortcomings including resistance, inefficiency, higher dose, side effects and costs. The goal of the current investigation was to assess the antioxidant capacity and antidiabetic activity of an ethanolic extract of Zanthoxylum rhetsa root bark (ZRRB) through in vitro, in vivo, and in silico methods. The antioxidant capacity of the ZRRB extract was measured using both the DPPH radical assay and the total antioxidant activity test. The oral glucose tolerance test (OGTT) and alloxan-induced diabetic mice model were also used to examine in vivo antidiabetic efficacy. Phytochemicals identification was done by GCMS analysis. Additionally, computational methods such as molecular docking, ADMET analysis, and molecular dynamics (MD) modeling were performed to determine the above pharmacological effects. The extract demonstrated significant DPPH scavenging activity (IC50 = 42.65 μg/mL). In the OGTT test and alloxan-induced diabetes mice model, the extract effectively lowered blood glucose levels. Furthermore, in vitro inhibition of pancreatic α-amylase studies demonstrated the ZRRB extract as a good antidiabetic crude drug (IC50 = 81.45 μg/mL). GCMS investigation confirmed that the crude extract contains 16 major phytoconstituents, which were docked with human peroxiredoxin-5, α-amylase, and sulfonylurea receptor 1. Docking and pharmacokinetic studies demonstrated that among 16 phytoconstituents, 6H-indolo[3,2,1-de] [1,5]naphthyridin-6-one (CID: 97176) showed the highest binding affinity to targeted enzymes, and imitated Lipinski's rule of five. Furthermore, MD simulation data confirmed that the aforementioned compound is very steady to the binding site of α-amylase and sulfonylurea receptor 1 receptors. Findings from in vitro, in vivo and in silico investigation suggest that ZRRB extract contains a lead compound that could be a potent source of antidiabetic drug candidate.

Project description:Annona reticulata L. (Bullock's heart) is a pantropic tree commonly known as custard apple, which is used therapeutically for a variety of maladies. The present research was carried out to evaluate the possible protective effects of Annona reticulata L. (A. reticulata) ethanolic seed extract on an experimentally induced type 2 diabetes rat model. Male Albino Wistar rats were randomly divided into five groups with six animals in each group viz., control rats in group I, diabetic rats in group II, diabetic rats with 50 and 100 mg/kg/bw of ethanolic seed extract of A. reticulata in groups III and IV, respectively, and diabetic rats with metformin in group V. Treatment was given for 42 consecutive days through oral route by oro-gastric gavage. Administration of A. reticulata seed extract to diabetes rats significantly restored the alterations in the levels of body weight, food and water intake, fasting blood glucose (FBG), insulin levels, insulin sensitivity, HbA1c, HOMA-IR, islet area and insulin positive cells. Furthermore, A. reticulata significantly decreased the levels of triglycerides, cholesterol, LDL, and significantly increased the HDL in diabetic rats. A. reticulata effectively ameliorated the enzymatic (ALT, AST, ALP, GGT) and modification of histopathological changes in diabetic rats. The serum levels of the BUN, creatinine levels, uric acid, urine volume, and urinary protein were significantly declined with a significant elevation in CCr in diabetic rats treated with A. reticulata. MDA and NO levels were significantly reduced with an enhancement in SOD, CAT, and GPx antioxidant enzyme activities in the kidney, liver, and pancreas of diabetic rats treated with A. reticulata. Diabetic rats treated with A. reticulata have shown up-regulation in mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H:quinone oxidoreductase 1 (NQO1), Heme oxygenase-1 (HO-1) and protein expression level of Nrf2 with diminution in Keap1 mRNA expression level in pancreas, kidney, and liver. From the outcome of the current results, it can be inferred that seed extract of A. reticulata exhibits a protective effect in diabetic rats through its anti-diabetic, anti-hyperlipidemic, antioxidant and anti-inflammatory effects and could be considered as a promising treatment therapy in the treatment of diabetes mellitus.

Dataset Information

Antidiabetic Effects of the Ethanolic Root Extract of Uvaria chamae P. Beauv (Annonaceae) in Alloxan-Induced Diabetic Rats: A Potential Alternative Treatment for Diabetes Mellitus.

Publications

Antidiabetic Effects of the Ethanolic Root Extract of <i>Uvaria chamae</i> P. Beauv (Annonaceae) in Alloxan-Induced Diabetic Rats: A Potential Alternative Treatment for Diabetes Mellitus.

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