Quercetin modulates hyperglycemia by improving the pancreatic antioxidant status and enzymes activities linked with glucose metabolism in type 2 diabetes model of rats: In silico studies of molecular interaction of quercetin with hexokinase and catalase

Abstract

Quercetin was assessed for its antihyperglycemic effect in fructose-streptozotocin (STZ) induced diabetic rats. The oral administration of quercetin at the dosage of 25 and 50 mg/kg for 28 days remarkably reduced the level of blood glucose, glycosylated hemoglobin (Hb), and hepatic glycogen but enhanced plasma Hb concentration. The altered activities of glucose-6-phosphatase and hexokinase in diabetic rats were significantly improved upon quercetin treatment. Furthermore, the antioxidant activity of pancreatic superoxide dismutase, catalase (CAT), and reduced glutathione was effectively increased while the value for thiobarbituric acid reactive species was decreased. A significant reduction of glycemia was observed in the glucose tolerance test, 120 min after the glucose pulse. Also, the damage caused by fructose-STZ in the liver and pancreas of diabetic animals were restored to near normal. Molecular docking of quercetin showed a high affinity for hexokinase and CAT with a binding energy of −7.82 and −9.83 kcal/mol, respectively, more elevated than the standard drugs. Practical applicationsFunctional foods and nutraceuticals have increasingly interested the consumers in terms of health benefits and have started focussing on the prevention or cure of disease by the foods and their health-enhancing phytochemicals. Quercetin is one of the most potent naturally occurring antioxidants within the flavonoid subclasses, mostly distributed as a secondary metabolite in fruits, vegetables, and black tea.Based on the results exhibited in the present study, we proposed that the consumption of foods rich in quercetin could be a cheap and affordable nutraceutical that can be developed for the treatment of T2DM and its complications. Further studies on the safety aspects of quercetin in long-term usage are strongly recommended before implementing for the treatment of human diseases. | MATERIAL S AND ME THODS | Chemicals and reagentsThe compounds 3,5,7,3,4, pentahydroxy flavones (quercetin), STZ, potassium hydroxide (KOH), cyanmethemoglobin, trichloroacetic acid (TCA), sulfuric acid (H 2 SO 4 ), HPLC grade ethanol, potassium chloride (KCl), ethylenediaminetetraacetic acid (EDTA), ammonium molybdate {(NH4) 6 Mo 7 O 24 }, ammonium acetate (NH 4 CH 3 CO 2 ), K E Y W O R D S anti-hyperglycaemic, antioxidant, glucose metabolism, histopathology, molecular docking, Quercetin | 3 of 16 OYEDEMI Et al.amino naphthol sulfonic acid (C 10 H 9 NO 4 S), Tris-HCl buffer, citrate buffer, sucrose, glucose, and Drabkin reagents purchased from Merck Chemicals (Pty) Ltd., Bellville, South Africa. All other chemicals and reagents were of analytical grade and procured from Sigma-Aldrich Chemical Co. (Johannesburg-SA).

Protective Effects of Quercetin/Moss Extract (Homalothecium Sericeum Hedw.) Combination on STZ-Induced Diabetic Rats

“…There were significant increases in glycosylated hemoglobin, lipids, and oxidative stress biomarker levels in the diabetic group compared to non-diabetics. The findings support the association between type 2 diabetes and hyperglycemia-induced oxidative stress, chronic hyperglycemia, and type 2 diabetes progression [13].…”

“…This effect may be related to improving whole-body insulin sensitivity by increasing the expression and phosphorylation of glucose transport-4 and insulin receptors and substrate [12]. Quercetin also increases blood glucose uptake by hepatic cells by activating hexokinase and adenosine monophosphate-activated protein kinase [13]. In addition, quercetin was reported to lower blood sugar by increasing the proliferation of pancreatic β-cells in STZ-induced diabetic rats [34].…”

A Network Pharmacology Approach to Investigate the Mechanism of Erjing Prescription in Type 2 Diabetes

“…Quercetin, β-sitosterol, diosgenin, baicalein, and 3′-methoxydaidzein were found as the potential composition of treating diabetes in EJP. e hyperglycemia was modulated through regulating the enzymes activities as for metabolism in glucose and improving the antioxidant status of pancreatic in rats of T2DM model from the results of Oyedemi' studies [42]. Quercetin can be used for the treatment of T2DM by lowering the pancreatic iron deposition and PBC ferroptosis [43].…”

Polyphenols and Flavonoids Composition, Anti-Inflammatory and Antioxidant Properties of Andean Baccharis macrantha Extracts

“…Many food plants have quercetin flavonoids and are reported to have protective effects against Alzheimer disease in human patients and mouse models [61]. Oyedemi et al [62] reported quercetin with the capacity to reduce hyperglycemia in a type 2 diabetes rat model.…”