Isopulegol Mitigates Hyperglycemia Mediated Oxidative and Endoplasmic Reticulum Stress in HFD/STZ Induced Diabetic Rats

Abstract

Oxidative and endoplasmic reticulum stresses contribute to the pathogenesis of β-cell dysfunction in diabetes mellitus. This study investigates the effect of isopulegol on the above stresses in HFD/STZ induced diabetic rats. Animals in group I and II were placed in normal pellet diet and group II was treated with isopulegol at 200mg/kg b.w. Animals in groups III-V were placed in HFD for 4weeks and made diabetic with single intraperitoneal injection of STZ (35mg/kg b.w) in 0.1M citrate buffer (pH 4.5). Group III served as diabetic control while animals in group IV and V were treated with isopulegol (100mg/kg b.w) and metformin (25mg/kg b.w) respectively for 28d. The activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione sulphur transferase (GST), glutathione reductase (GR) and the levels of vitamin-E, vitamin-C, reduced glutathione (GSH) were significantly (p <0.05) decreased in plasma and tissues of diabetic rats. Thiobarbituric acid reactive acid substances (TBARS) and lipid hydroperoxides (LHP), indices of lipid peroxidation were also significantly (p <0.05) increased in diabetic rats. In pancreatic tissue ER stress markers PERK, elf2α, ATF4 and in hepatic tissue oxidative stress marker UCP-2 expression was significantly (p <1.0) increased in diabetic rats. Administration of isopulegol significantly improved antioxidant status and decreased oxidative and ER stress markers in diabetic treated rats. Histopathological studies on liver and kidney supported the above findings. The results are comparable with the standard drug metformin. Isopulegol a naturally occurring monoterpene alcohol attenuated oxidative and ER stress in HFD/STZ induced diabetic rats.