Safoura Alizade - Department of Sport Sciences, Shahrekord University, Shahrekord, Iran
Mohammad Faramarzi - Department of Exercise Physiology, Faculty of Sport Sciences, University of Isfahan, Isfahan, Iran
Ebrahim Banitalebi - Department of Sport Sciences, Shahrekord University, Shahrekord, Iran
Elham Saghaei - Department of Pharmacology, Shahrekord University of Medical Sciences, Shahrekord, Iran

Objective(s): The increase in age-related cognitive impairment (CIs) and diabetes mellitus is a global health concern. Exercise training has been reported to activate the Nrf۲/Keap۱/ARE signaling and enhance the antioxidant defense pathways in some animal models. This study aimed to investigate the effects of ursolic acid (UA) associated with resistance or endurance training on antioxidant markers, and the Nrf۲/Keap۱/ARE pathway in the brain of older diabetic rats.Materials and Methods: ۲۳-month-aged diabetes induced male Wistar rats were randomly assigned to seven groups (n=۸). UA supplementation (۲۵۰ mg/kg, daily) was administered along with resistance (۶۰% maximum capacity of voluntary carrying [MVCC], ۱۴-۲۰ climbs) or endurance training (۶۰-۷۵% velocity at maximal oxygen uptake [vVO۲max]), five days/week for eight weeks. Cognitive-motor functioning was assessed through open-field and passive avoidance response tests. Nrf۲, Keap۱, and antioxidant markers including SOD, CAT, GPx, and GSH were measured in the hippocampus tissue.Results: The results showed positive effect of resistance training (P≤۰.۰۰۱) on Nrf۲. There was endurance training with supplementation main effect (P=۰.۰۱۸) on Keap۱ concentration. SOD revealed a significant endurance/resistance training by supplementation interaction effect (P≤۰.۰۵); however, there was no main training or UA supplementation effects on CAT, GPx, and GSH, despite improving spatial memory changes in exercise or UA groups. Conclusion: It appears that UA treatment with resistance or endurance exercise has some beneficial effects on Nrf۲ and some antioxidant markers. However, more research is needed to elucidate UA’s interaction effects and exercise interventions in diabetic situations.

Cognitive impairment, Diabetes, Hippocampus, Nrf۲/Keap۱/ARE signaling, Training, Ursolic acid