STUDIES ON THE ROLE OF NRF2 ACTIVATOR NARINGENIN IN EXPERIMENTAL DIABETES

Abstract

quotABSTRACT newlineStudies on the role of Nrf2 activator-naringenin in experimental diabetes newlineThe objectives of the present study include: newline1) Determine the antioxidant potential of naringenin using in vitro antioxidant assay methods newline2) Study the effect of naringenin on Nrf2 activation in MIN6 pancreatic and#946;-cell line newline3) Evaluate the ability of elevated Nrf2 to mitigate STZ-treatment induced pancreatic and#946;-cell apoptosis in MIN6 cells newline4) Assess the efficacy of Nrf2-upregulatingnaringenin for protecting mice from STZ-induced diabetes newline newlineThe free radical scavenging activity of naringenin was evaluated by measuring its effect on (a) hydroxyl; (b) superoxide; (c) hydrogen peroxide; (d) nitric oxide; and (e) DPPH radicals as well as for inhibiting the peroxidation of lipids. newlineThe ability of naringenin to activate Nrf2 was assessed using Nrf2-Keap1 complementation system in MIN6 cells. Immunoblot analysis was performed to detect the Nrf2 in cytosolic and nuclear extracts. Anti-apoptotic activity of naringenin was evaluated by estimating the levels of caspase-3 and Annexin V expression. Anti-diabetic potential of naringenin was assessed by in the pancreas, liver and kidney homogenates prepared from animals treated with multiple low dose streptozotocin (MLD-STZ) for 5 consecutive days (i.p). In addition, the potential of naringenin to modulate the activities of key carbohydrate metabolizing enzymes and glycogen content in liver was also assessed. newline newlineIn conclusion, results of this study demonstrate the potential of naringenin for promoting the expression of anti-oxidant regulator Nrf2 and its target genes, while modulating the levels of carbohydrate metabolizing enzymes to treat diabetes. Hence, future studies should consider testing naringenin in higher animals to determine its potential for inhibiting experimental and spontaneous diabetes. newline newlineKEY WORDS:Diabetes, Streptozotocin, Naringenin, Nrf2, pancreatic and#946;-cells, Apoptosis. newline