INTRODUCTION

Type 2 diabetes is one of the most prevalent metabolic diseases, the main cause of which is the creation of a disorder called insulin resistance and, as a result, a defect in the entry of blood sugar into the tissue (1). This disease, which is usually more common in the elderly, is the most common subtype of diabetes, and similar to other types of this disease, one of its main symptoms is hyperglycemia (1). Along with the progress of diabetes, hyperglycemia causes disorders in the cardiovascular systems, kidney, retina, eye lens, skin, and central and peripheral nervous system (1). Diabetes damages both the central and peripheral nervous systems through the apoptosis of basal neurons, and the increase in blood sugar caused by diabetes results in severe microvascular complications, such as neuropathy, nephropathy, and retinopathy. The most common complications of diabetes are diabetic neuropathies, which include disorders of the autonomic nervous system and the voluntary nervous system (2). Finally, neurological disorders in patients with diabetes are associated with an increase in brain tissue atrophy (3). In particular, it has been reported that hyperglycemia has destructive effects on special areas of the brain, such as hippocampal neurons, and causes defects in learning, memory, and problem-solving ability, as well as mental-motor and cognitive disorders in diabetic people (4). Nonetheless, the prevalence of neurodegenerative diseases among patients with type 2 diabetes is increasing, and currently, approximately 20% of neurodegenerative diseases are related to type 2 diabetes (5). One of the critical mechanisms through which exercise can affect the health of the central nervous system is the secretion of some proteins in the central nervous system. One of the important factors in this category is a glycoprotein named protein 5 containing fibronectin type III domain (FNDC5), which has been well recognized in the past for its neuroprotective effects (6). Therefore, it seems that the consumption of medicinal plant extracts along with physical activity is a valuable treatment solution for diabetes owing to its few side effects and high efficiency, highlighting research in this area. Therefore, due to the synergism of drug treatment and exercise, the present study aimed to assess the effect of saffron aqueous extract consumption during resistance training on blood glucose levels and FNDC5 protein levels in the hippocampus of type 2 diabetic rats.

METHODS

Adult male Sprague-Dawley rats were used in this experimental study. Diabetes was induced by intraperitoneal injection of streptozotocin solution dissolved in fresh citrate buffer [2]. The rats were randomly assigned into five equal groups based on blood glucose: control (C), diabetes (D), diabetes-resistance training (DT), diabetes-saffron extract (DS), and diabetes-resistance training-saffron extract (DTS). DT and DTS groups performed resistance training five days a week. In this study, 25 mg of saffron extract per kilogram of body weight was administered to DS and DTS groups daily by gavage at 8 a.m. Finally, blood glucose levels and hippocampus FNDC5 protein levels were measured.

RESULTS

Blood glucose levels were significantly higher in all groups than in the C group (P=0.001). Blood glucose levels in the DT, DS, and DTS groups were significantly lower than those in the D group (P=0.001). Moreover, in the DTS group, the blood glucose levels were significantly lower than in the DT group (P=0.014). FNDC5 protein levels of all groups were significantly lower than those in the C group (P<0.05). In addition, FNDC5 protein levels were significantly lower in the D and DS groups than in the DTS group (P<0.05). Nonetheless, the FNDC5 protein levels of the D and DS groups did not differ significantly (P=0.92); however, the FNDC5 protein levels of the D and DT groups displayed a significant difference (P=0.006).

Resistance training and the consumption of saffron extract alone and in combination with each other can reduce blood glucose levels in rats with type 2 diabetes. The consumption of saffron extract did not increase FNDC5 protein levels; however, resistance training alone and together with saffron consumption increased FNDC5 protein levels. Therefore, in order to control blood glucose levels and increase FNDC5 protein levels, it is suggested that saffron be consumed during resistance training in rats with type 2 diabetes.

Ethical Considerations

Compliance with ethical guidelines

All experiments in the current study followed the ethical principles approved by the Animal Ethics Committee of the Medical University of Kurdistan (reference number: IR. MUK.REC. 1398.5008).

Funding

All financial support for this article was provided by the Research Deputy of Lorestan University.

Authors’ Contributions

The authors contributed equally to the conceptualization and writing of the article. All of the authors approved the content of the manuscript and agreed on all aspects of the work.

Conflict of Interest

The authors declared no conflict of interest.

Acknowledgments

We are grateful to all those who helped us carry out this research project.