Protective Effect of Oleuropein on Memory Impairment and Oxidative Stress in Streptozotocin-Induced Diabetes Rats via Modulation of NF-kB and Nrf-۲ Pathways

Background & Objectives: Diabetes is the most common metabolic disease, associated with hyperglycemia and long-term complications. This study aimed to elucidate the anti-diabetic role of oleuropein (OLE) in a streptozotocin (STZ)-induced diabetic animal model. Materials & Methods: Adult male Wistar rats (۲۰۰–۲۵۰ g) were randomly divided into four groups: ۱) Control group, ۲) STZ group: diabetic rats that received STZ (۶۰ mg/kg), ۳) OLE ۵۰ group: diabetic rats treated with oral OLE at ۵۰ mg/kg of body weight daily for ۲۸ days, and ۴) OLE ۱۰۰ group: diabetic rats treated with oral OLE at ۱۰۰ mg/kg of body weight daily for ۲۸ days. Memory function and biochemical factors such as malondialdehyde (MDA) levels, glutathione peroxidase (GPx), and total thiol activity were evaluated in the rats' cerebral cortex and striatum tissues. Moreover, nuclear transcription factor-kappa B (NF-κB) and nuclear factor E۲-related factor ۲ (Nrf۲) pathway activation were determined in cerebral cortex and striatum tissues by real-time polymerase chain reaction (PCR). Results: Chronic administration of OLE ameliorated cognitive deficits and attenuated oxidative stress induced by diabetes. Additionally, OLE significantly prevented the activation of the pro-inflammatory marker NF-κB and downregulated Nrf۲ expression in STZ-induced diabetic rats. Conclusion: Our results confirm the significant protective role of OLE against STZ-induced diabetes in rats by up-regulating Nrf۲ signaling and enhancing antioxidant activity.

Keywords:

‎Diabetes , Oleuropein , Oxidative stress , Memory , Nrf-۲ , Rat