Cannabinoid-1-receptors (CB1R) are therapeutic targets for both the treatment of autoimmune diseases, such as multiple sclerosis (MS), and some related symptoms such as pain. The aim of this study was to evaluate the effect of aerobic training and two dosages of royal jelly (RJ) on hippocampal CB1R and pain threshold (PT) in an experimental autoimmune encephalomyelitis (EAE) model. To this end, 56 female Sprague-Dawley rats with EAE were randomly assigned to one of the following eight conditions: (1) EAE; (2) sham; (3) 50 mg/kg RJ (RJ50); (4) 100 mg/kg RJ (RJ100); (5) exercise training (ET); (6) ET + RJ50; (7) ET + RJ100; and (8) not EAE or healthy control (HC). Endurance training was performed for five weeks, four sessions per week at a speed of 11–15 m/min for 30 min, and RJ was injected peritoneally at doses of 50 and 100 mg/kg/day). One-way analysis of variance and Tukey’s post hoc tests were performed to identify group-related differences in pain threshold (PT) and CB1R gene expression. Endurance training had no significant effect on PT and hippocampal CB1R in rats with EAE. CB1R gene expression levels in the RJ100 group were higher than in the EAE group. Further, PT levels in the ETRJ50 and ETRJ100 groups were higher than in the EAE group. The combination of ET and RJ50 had a higher impact on PT and CB1R, when compared to the ET and RJ50 alone. Next, there was a dose-response between RJ-induced CB1R gene expression and RJ dosages: higher dosages of RJ increased the CB1R gene expression. The overall results suggest that the combination of ET and increasing RJ dosages improved pain threshold probably related to CB1R in an EAE model, while this was not observed for ET or RJ alone.
Background: Although the beneficial role of training and the use of some antioxidants in physiological and psychological disorders in autoimmune diseases has been reported, the simultaneous effect of aerobic training (AT) and royal jelly (RJ) with different doses is not well understood. The present study aimed to investigate the effect of AT and RJ on inflammatory factors, hippocampus and psychological functions in the experimental autoimmune encephalomyelitis (EAE).Methods: Sprague-Dawley rats with EAE were assigned to seven groups: (1) EAE, (2) sham (Sh), (3) 50 mg / kg RJ (RJ50), (4) 100 mg / kg RJ (RJ100), (5) AT, (6) AT + RJ50, and (7) AT + RJ100 and healthy control. Results: AT decreased IL-17, TGF-β gene expression and immobilization time, while it increased IL-10, OAT% and OAR% compared to the EAE group. RJ50 and RJ100 decreased IL-17, IL-23 gene expression, and immobilization time, and increased IL-10 and OAR% compared to the EAE group. AT + RJ50 and AT + RJ100 decreased IL-17, IL-23, TGF-β, and immobilization time, while increased IL-10 and OAT% compared to the EAE group. The effect of AT + RJ100 on decreasing IL-17, IL-23, immobilization time, increasing TGF-β, IL-10, and OAR% was more favorable than RJ50. Conclusion: AT and RJ improved inflammatory factors and reduced anxiety and depression. The synergistic effect of two interventions, especially using higher doses of RJ were more favorable.
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