en علوم مولکولی Molecular Sciences تحقیقی Original article <div style="text-align: justify;"><span style="font-size:12px;"><span style="font-family:Times New Roman;"><b>Background:</b> Diabetes mellitus (DM) is a chronic metabolic disorder associated with reduced neurotrophic factors such as Brain-Derived Neurotrophic Factor (BDNF) and Nerve Growth Factor (NGF) in peripheral tissues. This study aimed to investigate the effects of eight weeks of Low-Intensity Continuous Training (LICT) and High-Intensity Interval Training (HIIT) combined with crocin administration on BDNF and NGF gene expression in the gastrocnemius muscle of diabetic rats induced by a High-Fat Diet (HFD).<br> <b>Methods:</b> In this experimental study, 42 male Sprague-Dawley rats (Mean weight 229 &plusmn; 8.9 g) were fed a high-fat diet for 8 weeks, followed by a single intraperitoneal injection of streptozotocin (STZ, 30 mg/kg) to induce type 2 diabetes. The rats were randomly divided into six groups (n=7): (1) Diabetic Control, (2) Crocin (25 mg/kg daily), (3) LICT, (4) HIIT, (5) LICT + Crocin, and (6) HIIT + Crocin. Crocin (Or saline) was injected 2 hours prior to each training session. The training protocols were performed on a rodent treadmill in five sessions per week for eight weeks. Forty-eight hours after the final session, gastrocnemius muscle tissue was extracted, and BDNF and NGF gene expression levels were measured using Real-Time PCR. The sample size was calculated using G-Power (Power = 0.80, &alpha; = 0.05), and blinding was applied during injections and PCR analyses. Data were analyzed using one-way ANOVA and Bonferroni post-hoc tests. The level of statistical significance was set at 0.05.<br> <b>Results:</b> One way ANOVA revealed significant effects of interventions on BDNF (F5,36 = 7.480, P-Value < 0.001) and NGF (F5,36 = 10.291, P-Value < 0.001) gene expression. Although the study was not designed to formally test interaction effects, the combination groups (LICT+Crocin and HIIT+Crocin) consistently showed higher mean values compared to single intervention groups, suggesting an additive or potentiating effect. Post-hoc analysis indicated that the HIIT + Crocin group exhibited significantly higher BDNF and NGF gene expression compared to all other groups (P-Value < 0.05). The LICT + Crocin group also showed significant increases compared to the control and single intervention groups. A comparison between LICT+Crocin and HIIT-only showed a trend toward significance but did not reach statistical significance (P-Value = 0.065).<br> <b>Conclusion</b>: The combination of exercise training and crocin, particularly the combined effect of High-Intensity Interval Training with crocin, significantly upregulates BDNF and NGF gene expression in the skeletal muscle of diabetic rats. This combined strategy may serve as a potential adjunctive approach for improving the muscular neurotrophic environment in diabetes. Future studies with factorial designs are needed to confirm synergistic interactions.</span></span></div> Type 2 Diabetes, Crocin, High-Intensity Interval Training, Brain-Derived Neurotrophic Factor, Nerve Growth Factor, Gene expression 0 0 http://goums.ac.ir/jorjanijournal/browse.php?a_code=A-10-700-5&slc_lang=en&sid=1 Somayyeh Norouzi f.sport2000@gmail.com 100319475328460011054 0009-0009-7199-4659 No Department of Sport Physiology, Marv.C., Islamic Azad University, Marvdasht, Iran Iman Fathi imanfathi@gmail.com 100319475328460011055 100319475328460011055 Yes Department of Sport Sciences, Faculty of Literature and Humanities, Vali-e-Asr University of Rafsanjan, Rafsanjan, Iran Seyyed Ali Hosseini alihoseini_57@yahoo.com 100319475328460011056 100319475328460011056 No Department of Sport Physiology, Marv.C., Islamic Azad University, Marvdasht, Iran