The Effect of Saffron Extract Supplementation During Resistance Training on Hippocampal Doublecortin and Hepatic β-Hydroxybutyrate Levels in Rats With Type 2 Diabetes

Abstract

Background: Type 2 diabetes mellitus (T2DM) negatively affects metabolic and neurobiological processes, including increases in hepatic β-hydroxybutyrate (BHB) and reductions in hippocampal doublecortin (DCX). Both saffron extract and resistance training have shown independent benefits in improving glycemic and neuroplastic markers; however, their combined effects on DCX and BHB in diabetic conditions have not been fully examined. This study evaluated the independent and synergistic effects of saffron extract supplementation and resistance training on glucose, hippocampal DCX, and hepatic BHB levels in rats with T2DM.

Methods: Thirty adult male rats were randomly assigned to five groups (n = 6 each): control (C), diabetic (D), diabetic with resistance training (DT), diabetic with saffron extract (DS), and diabetic with resistance training plus saffron extract (DTS). Diabetes was induced using streptozotocin (60 mg/kg). Saffron extract (25 mg/kg/day) was administered orally in the DS and DTS groups, and resistance training was performed five sessions per week for 6 weeks. Blood glucose, hippocampal DCX, and hepatic BHB levels were measured. Data were analyzed using one-way ANOVA with a significance threshold of p < 0.05.

Results: Both saffron extract and resistance training independently reduced glucose levels compared with the diabetic group, whereas the combined intervention produced the greatest reduction. DCX levels were significantly higher in the DTS group than in the D, DT, and DS groups (p < 0.05). BHB levels in the DT, DS, and DTS groups were significantly lower than in the D group, with the lowest levels observed in the DT and DTS groups (p < 0.05).

Conclusion: Saffron extract combined with resistance training more effectively improves glucose regulation, increases hippocampal DCX expression, and reduces hepatic BHB levels in T2DM rats compared with either intervention alone.

Keywords: Type 2 diabetes mellitus; doublecortin; neurogenesis; resistance training; saffron; β-hydroxybutyrate.