Exercise and Urtica Dioica extract ameliorate mitochondrial function and the expression of cardiac muscle Nuclear Respiratory Factor 2 and Peroxisome proliferator-activated receptor Gamma Coactivator 1-alpha in STZ-induced diabetic rats

Abstract

Introduction: Diabetes mellitus can affect and disrupt the levels of PGC1α and NRF2 proteins in the mitochondrial biogenesis pathway. Considering the anti-diabetic properties of Urtica Dioica extract and exercise, this study aimed to investigate the beneficial effects of Urtica Dioica extract and endurance activity on PGC1α and NRF2 protein levels in the streptozotocin-induced diabetic rat heart tissue.

Materials and methods: 58 male Wistar rats were divided into five groups (N = 12) including: healthy control (HC), diabetes control (DC), diabetes Urtica Dioica (D-UD), diabetes exercise training (DT), and diabetes exercise training Urtica Dioica (DT-UD). Diabetes was induced intraperitoneally by STZ (45 mg/kg) injection. Two weeks after the induction of diabetes, the rats were stimulated to carry out the exercise (moderate intensity/5day/week) and the gavage of UD extract (50 mg/kg/day) was administered to the rats for six weeks. In this study, the western blotting method was used to measure the levels of PGC1α and NRF2 proteins. Moreover, cardiography was used to evaluate the functional parameters of the heart (ejection fraction & fractional shortening). Finally, the bioluminescence and ELISA methods were used to determine the content of adenosine triphosphate and citrate synthase.

Results: The cardiac function parameters, the mitochondrial ATP and the CS content in DC group mice were impaired in comparison with the other study groups and showed a decreasing trend (P < 0.001). The treatment with EX + UD extract was able to minimize the rate of these disorders and acted as a protector of mitochondrial function. There were significant differences in the expression levels of NRF2 (F = 17.7, P = 0.001) and PGC-1α (F = 43.7, P = 0.001) mitochondrial proteins among the different groups. The levels of these proteins were significantly reduced in the DC group in comparison with the HC group (P < 0.001). The treatment with EX or UD extract increased the expression of PGC-1α and NRF2 proteins in the heart muscle of animals in the DT and D-UD groups in comparison with the DC group (P < 0.05). Moreover, the expression of these proteins was more pronounced in the DT-UD group. There was not a significant difference between the DT-UD group and the HC group regarding the expression of these proteins (P > 0.05).

Conclusions: The results of this study showed that treatment with EX and UD extract could treat the disorders which were caused by diabetes in the parameters of cardiac function. Moreover, it was able to improve the expression of the levels of proteins which were involved in mitochondrial biogenesis and its function. Finally, this kind of treatment could attract more attention to the roles of EX and UD extract in the prevention of cardiovascular complications in future studies.

Keywords: Diabetes; Exercise; Heart; NRF2; PGC1α; Urtica Dioica.