pelargonidin and Hyperglycemia

A novel strategy for the isolation of anthocyanins was developed by a combination of high-speed countercurrent chromatography (HSCCC) and HPLC techniques. Using this strategy, a novel α-glucosidase inhibitor (pelargonidin-3-O-rutinoside, a natural anthocyanin) was isolated from strawberries. Structural determinants for inhibition of α-glucosidase by Pg3R and the SAR of natural anthocyanins were revealed in detail by enzymatic kinetics and molecular docking analysis.

Topics: Administration, Oral; alpha-Glucosidases; Animals; Anthocyanins; Area Under Curve; Binding Sites; Blood Glucose; Catalytic Domain; Fragaria; Glucose Tolerance Test; Glycoside Hydrolase Inhibitors; Hyperglycemia; Inhibitory Concentration 50; Kinetics; Mice; Mice, Inbred ICR; Molecular Docking Simulation; ROC Curve; Structure-Activity Relationship

Alloxan is an environmental food contaminant that causes DNA damage in living cells and induces hyperglycemia. Pelargonidin (PG), an active ingredient found in extract of various fruits and vegetables, has been nanoencapsulated (NPG) with poly-lactide-co-glycolide (PLGA) and tested for efficacy in prevention of alloxan (ALX)-induced DNA damage in L6 cells in vitro. Glucose uptake, reactive oxygen species (ROS) generation, glucose transporter 4, glucokinase levels and mechanism of activation of DNA repair proteins (PARP and p53) have been studied in ALX-induced L6 cells. Drug-DNA interaction has been analyzed using calf thymus DNA as target through circular dichroism and melting temperature profile. NPGs were physico-chemically characterized by standard protocols using dynamic light scattering and transmission electron microscopy. Pre-treatment with both PG and/or NPG was effective in reducing ALX-induced oxidative stress and showed favourable effects for protection against DNA damage by activating DNA repair cascades. Results suggested ∼10-fold increase in efficacy of NPG than PG in prevention of alloxan-induced oxidative stress and DNA damage.

Topics: Alloxan; Animals; Anthocyanins; Cell Line; DNA Damage; Hyperglycemia; Nanoparticles; Oxidative Stress; Poly (ADP-Ribose) Polymerase-1; Protective Agents; Rats; Tumor Suppressor Protein p53

Glycation-modified hemoglobin in diabetes mellitus has been suggested to be a source of enhanced catalytic iron and free radicals causing pathological complications. The present study aims to verify this idea in experimental diabetes. Pelargonidin, an anthocyanidin, has been tested for its antidiabetic potential with emphasis on its role against pathological oxidative stress including hemoglobin-mediated free radical reactions. Male wistar rats were grouped as normal control, streptozotocin-induced diabetic control, normal treated with pelargonidin and diabetic treated with pelargonidin. Pelargonidin-treated rats received one time i.p injection of the flavonoid (3 mg/kg bodyweight). Biochemical parameters were assayed in blood samples of different groups of rats. Liver was used for histological examinations. Pelargonidin treatment normalized elevated blood glucose levels and improved serum insulin levels in diabetic rats. Glucose tolerance test appeared normal after treatment. Decreased serum levels of SOD and catalase, and increased levels of malondialdehyde and fructosamine in diabetic rats were reverted to their respective normal values after pelargonidin administration. Extents of hemoglobin glycation, hemoglobin-mediated iron release, iron-mediated free radical reactions and carbonyl formation in hemoglobin were pronounced in diabetic rats, indicating association between hemoglobin glycation and oxidative stress in diabetes. Pelargonidin counteracts hemoglobin glycation, iron release from the heme protein and iron-mediated oxidative damages, confirming glycated hemoglobin-associated oxidative stress in diabetes.

Topics: Animals; Anthocyanins; Antioxidants; Diabetes Mellitus, Experimental; DNA; Fructosamine; Glucose; Glucose Tolerance Test; Hemoglobins; Hyperglycemia; Insulin; Iron; Liver; Male; Malondialdehyde; Oxidative Stress; Protein Carbonylation; Rats; Rats, Wistar; Superoxide Dismutase