Ursolic acid mitigates cognitive dysfunction through amelioration of oxidative stress, inflammation and apoptosis in diabetic rats

Abstract

Purpose: To determine the effect of ursolic acid (UA) on diabetes-induced cognitive defect, as well as its mechanism of action in streptozotocin (STZ)-induced diabetic rats. Methods: A rat model of diabetes was established by administration of STZ. The rats received UA via gastric perfusion for 56 successive days. Learning and memory functions were assessed using Morris water maze. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels in hippocampus tissues were determined spectrophotometrically. Tumor necrosis factor-a (TNF-a), interleukin-1β (IL-1β) and interleukin-6 (IL-6) levels were assayed by quantitative real-time polymerase chain reaction (qRT- PCR) and enzyme-linked immunosorbent assay (ELISA). The protein expression levels of nuclear factor erythroid-2-related factor-2 (Nrf-2), heme oxygenase-1 (HO-1), Bcl-2 and Bax were evaluated by western blotting. Results: Learning and memory impairment in STZ-induced diabetic rats was mitigated by UA (p < 0.05). In hippocampus tissue, UA reduced oxidative stress by enhancing SOD activity and reducing MDA levels. Furthermore, UA reduced inflammatory response by downregulating TNF-α, IL-1β and IL-6 levels (p < 0.05). Concomitantly, the lower protein concentrations of Nrf-2 and HO-1 were elevated by administration of UA. Furthermore, UA suppressed Bax/Bcl-2 ratio to ameliorate apoptosis (p < 0.05). Conclusion: UA reduces diabetes-induced hippocampal oxidative stress, inflammation and apoptosis. Thus, it might be a potential drug candidate for delaying diabetes-associated cognitive decline (DACD).