Introduction: Cognitive impairments resulting from metabolic alterations in menopausal and diabetic conditions are among the major causes of morbidity and mortality in the elderly. While the beneficial effects of aerobic exercise and natural antioxidants such as royal jelly (RJ) on these impairments have been suggested, their combined influence on neurotrophins and brain metabolism remains poorly understood.

Methods: In this study, 37 ovariectomized diabetic rats were randomly assigned to the following groups: (1) diabetic ovariectomized control (OVX+DM), (2) sham, (3) endurance training (ET), (4) royal jelly supplementation (RJ), and (5) combined ET and RJ (RJ+ET). Additionally, seven healthy rats were included as a healthy control group (HC). ET was performed five days per week for eight weeks at an intensity of 55–75 percent of maximal running speed. RJ was administered daily at a dose of 100 mg/kg.

Results: Gene expression of BDNF, TrkB, and insulin was significantly reduced, while glucose levels were elevated in the OVX+DM group (P≤0.05). RJ and ET+RJ interventions significantly increased BDNF and TrkB expression and decreased glucose levels (P≤0.05). Insulin levels increased significantly only in the RJ+ET group compared to the OVX+DM group. Furthermore, BDNF and TrkB expression was significantly higher in the RJ+ET group compared to the RJ group alone (P≤0.05).

Conclusion: The combined intervention of aerobic training and royal jelly appears to exert synergistic effects on glycemic and neurotrophic indices, suggesting that concurrent use may be more effective than either intervention alone.