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Investigation of Anthocyanidins and Anthocyanins for Targeting ?-Glucosidase in Diabetes Mellitus.

ABSTRACT: Anthocyanidins are bioactive compounds found mostly in colored plants and fruits. Consumption of anthocyanidin-rich foods has been shown to reduce the risk of diabetes. However, limited information is available regarding the inhibitory effect and interactions of anthocyanidins on ?-glucosidase, the key enzyme that controls diabetes through degrading carbohydrate. Therefore, we used computational docking analysis to investigate the degree and type of inhibition by ?-glucosidase, and the structural interactions of enzyme-selected anthocyanidins. The results suggested that anthocyanidins exhibit half maximal inhibitory concentration of 4?55 ?M; the strongest and weakest ?-glucosidase inhibitors were delphinidin and malvidin, respectively. Indeed, delphinidin inhibits ?-glucosidase in a mixed type, close to non-competitive manner with an inhibitory constant of 78 nM. Addition of a glycoside (glucoside or galactoside) at C3 on the C ring of delphinidin significantly decreased inhibitory activity, and addition of glycosides at C3 on the C ring and C5 on the A ring of delphinidin prevented all inhibitory activity. Molecular docking and free binding energy accurately confirmed the mode of inhibition determined by enzyme kinetics. These data will inform the use of alternative sources of anthocyanidins in functional foods and dietary supplements for prevention of diabetes. The results provide useful information for evaluating possible molecular models using anthocyanins/anthocyanidins as templates and ?-glucosidase as the key enzyme in management of diabetes.

SUBMITTER: Promyos N

PROVIDER: S-EPMC7541926 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Investigation of Anthocyanidins and Anthocyanins for Targeting α-Glucosidase in Diabetes Mellitus.

Promyos Natnicha N Temviriyanukul Piya P Suttisansanee Uthaiwan U

Preventive nutrition and food science 20200901 3

Anthocyanidins are bioactive compounds found mostly in colored plants and fruits. Consumption of anthocyanidin-rich foods has been shown to reduce the risk of diabetes. However, limited information is available regarding the inhibitory effect and interactions of anthocyanidins on α-glucosidase, the key enzyme that controls diabetes through degrading carbohydrate. Therefore, we used computational docking analysis to investigate the degree and type of inhibition by α-glucosidase, and the structura ...[more]

PMID: 33083375

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Project description:BackgroundPolysaccharides decrease the glucose level by inhibiting α-glucosidase enzyme which further increases the level of GLP-1 (Glucagon-like peptide 1) to increase the insulin level as per earlier reports.ObjectiveSimilar hypothesis was designed in present study to investigate the α-glucosidase enzyme inhibition and involvement of GLP-1 in antidiabetic mechanism of Acacia tortilis polysaccharides (AEATP) in diabetic rats. Isolated polysaccharides were analyzed for their chemical nature by using HPLC and FTIR method.Materials and methodsMale albino wistar rats were divided into control, diabetic, diabetic + voglibose, diabetic + glimepiride, diabetic+250, 500, 1000 mg/kg of AEATP, diabetic + glimepiride + voglibose, diabetic + glimepiride+ 250, 500 and 1000 mg/kg AEATP, diabetic + GLP-1 antagonist+250, 500 and 1000 mg/kg AEATP. Plasma glucose, insulin and active GLP-1 levels were measured 15 min after OGTT. Fasting blood glucose, Plasma triglycerides, glycated hemoglobin (HbA1c), Fasting insulin, pancreatic insulin content, ileum and colon GLP-1 content were assessed at 5th week. Association of alpha-glucosidase was also assessed with GLP-1 and insulin.ResultsAEATP significantly attenuated hyperglycemia by increasing insulin level in plasma and pancreas and increased active GLP-1 as well as insulin level in diabetic rats after OGTT. GLP-1 content was significantly increased in ileum and colon by inhibiting alpha-glucosidase. Involvement of GLP-1 in antihyperglycemic effect of AEATP was confirmed by using GLP-1 antagonist. Moreover, AEATP significantly improved dyslipidemia in diabetic rats. HPLC analysis of A. tortilis polysaccharide comprised four specific monosaccharides (Rhamnose, Glucuronic acid, glucose and galactose) and FTIR spectrum shown band at 3430.6 cm-1 (O-H stretching), 2940.3 cm-1 (C-H linkage), 1630.4 cm-1 (carbonyl stretching), 1410 cm-1 (uronic acid) and 1030.5 cm-1 (glycosidic linkage).ConclusionIt can be concluded that antidiabetic effect of AEATP is through the modulation of GLP-1 level in plasma and intestinal tissue via alpha glucosidase inhibition.

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Investigation of Anthocyanidins and Anthocyanins for Targeting ?-Glucosidase in Diabetes Mellitus.

Publications

Investigation of Anthocyanidins and Anthocyanins for Targeting α-Glucosidase in Diabetes Mellitus.

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