The Effect of Aerobic Training and Tribulus Terrestris Extract on Muscle Atrophy Indices and Oxidant-Pro-Oxidant Balance in Extensor Digitorum Longus Muscles of Type 2 Diabetic Desert Rats

Background & Aims: Performing normal daily activities requires sufficient muscle size and strength, and atrophy has a negative effect on the overall quality of life; So that the decrease in skeletal muscle mass leads to a decrease in human performance, long-term health and low quality of life. Diabetes is associated with the development of secondary complications in various organs, especially skeletal muscle atrophy. The aim of this study was to evaluate the effect of aerobic training and Tribulus terrestris extract on muscle atrophy indices and oxidant-pro-oxidant balance in extensor digitorum longus muscles of type 2 diabetic desert rats. Skeletal muscle is an important organ for glucose storage and metabolism, apart from being a power-producing machine. Considering the important role of exercise and physical activity along with herbal supplements in health and prevention and treatment of complications caused by diabetes, especially in the vital organs of the body such as skeletal muscles, it seems that investigating the effects of sports activities and herbal supplements on The markers of muscle atrophy are of great importance, but according to the investigations, the data in this regard are very limited. Methods: For implementation of this experimental research, 42 male wistar desert rats 2 months old (average weight 180±20 g) were randomly divided into 7 groups. In order to induce muscle atrophy, Dexamethasone (750 μg/kg/day) was injected intraperitoneally into desert rats. desert Rats were diabetic using peritoneal injection nicotinamide-STZ. desert Rats in supplemented groups received Tribulus terrestris hydroalcoholic extract with doses of 5 and 10 mg per day by gavage method. Aerobic training was performed on a treadmill at a speed of 23 m/min, 30 min/day, 5 days/week for eight weeks. Using Real Time PCR and PAB methods, plantar muscle tissue was measured using immunoassay method. Shapiro-Wilk test was used to ensure the normal distribution of variables. Two-way analysis of variance and Bonferroni's post hoc test were used to compare the average changes of the investigated factors in the groups. The significance level was considered as p≤0.05 in all cases. All statistical operations were performed with SPSS software version 23. Results: Thistle plant extract (F=136.305, P=0.001, µ=0.901) and the interaction between training and thistle plant extract (F=419.949, P=0.001, µ=0.966) had a significant effect on the level of MURF-1 in extensor digitorum longus muscle. . Also, the amount of MURF-1 in the long extensor muscle of the toes with the 5-gram dose was significantly lower than the 10-gram dose group (P=0.0001). The results showed that aerobic training, Tribulus extract and combined intervention of Tribulus extract with aerobic training resulted in a significant decrease in the expression genes of Atrogin-1, MURF-1, MiR-29b (p=0.001) and significant increase in methyl guanine (p=0.001) and oxidant-pro-oxidant balance (PAB) levels in male wistar desert rats exposed to dexamethasone (p=0.001). Conclusion: The findings of this research show that aerobic training led to a significant decrease in Atrogin-1, MURF-1 and MiR-29b gene expression and a significant increase in methylguanine levels and oxidant-prooxidant balance in type 2 diabetic rats. Aerobic exercise has been shown to reduce DNA damage caused by oxidants. Decreased insulin and increased oxidative stress seem necessary for protein breakdown and muscle atrophy. Therefore, negative regulation of anabolic processes as well as oxidative stress occurred in STZ-treated animals can activate muscle proteolysis and increase MuRF1 expression. Regarding the effect of exercise on the expression of MuRF1 in type 2 diabetic samples, there have been few studies that have expressed different mechanisms in the interpretation of the results; The response of MuRF1 to sports activity can change under the influence of various factors, including the subjects' training history, the intensity and duration of the activity, or the effect of repeated activities. On the other hand, it seems that Hsp25 is one of the mediators that regulate the atrophy pathway, which plays an important role in dealing with atrophy in diabetic conditions, so that increasing its amount due to exercise reduces atrophy and decreases the expression of MuRF1. The mechanism of MiR-29b changes due to exercise training is not well defined. However, miR-29 targets have been found to include IGF-1, p85a, and myeloblastosis-related protein B (B-myb) in mouse muscle tissue. IGF-1 and p85a are important regulatory proteins for protein translation via miR-29 to inhibit myogenin and protein synthesis, thereby reducing protein components during muscle atrophy. The effect of exercise on redox status depends on many factors, such as type of exercise, exercise load, as well as age, gender, risk factors, and physical condition. Short-term exercises may increase oxidative stress and imbalance between ROS production and antioxidant agents and ultimately lead to mitochondrial dysfunction. However, long-term exercise may enable ROS detoxification by increasing cellular antioxidant activity or stimulating the expression of genes such as Mn-SOD. Other findings of the research show that milk thistle extract and the interaction of exercise and milk thistle extract reduce Atrogin-1, MURF-1 and MiR-29b gene expression and increase methylguanine levels and oxidant-prooxidant balance in the extensor toes long muscle tissue in rats. He had type 2 diabetes. Other findings of the research show that milk thistle plant extract and the interaction of milk thistle plant extract with the reduction of Atrogin-1, MURF-1 and MiR-29b gene expression and the increase of methylguanine levels and the oxidant-prooxidant balance of the extensor digitorum longus muscle tissue in diabetic rats. Type 2 was included. It has been determined that the extract of this plant has hypoglycemic and hypolipidemic properties in the experimental model of diabetes mellitus induced by streptozotocin. In the present study, the hydroalcoholic extract of thistle plant with doses of 5 and 10 mg per kilogram of body weight per day was able to help reduce muscle atrophy in type 2 diabetic rats, and the lower dose brought more benefits. Due to the presence of large amounts of alkaloids, polyphenols, flavonoids, as well as the antioxidant, hypoglycemic and hypolipidemic properties of milk thistle, and based on the findings of this research, it can be said that the presence of antioxidants in milk thistle can reduce muscle atrophy. The inhibitory effect of regular exercise is also at least partly due to adaptation to oxidative stress. The process of adaptation related to exercise is not only related to the production of ROS levels, but also causes an increase in antioxidants and the activity of enzymes that restore the damage caused by oxidative damage (43). Therefore, the interaction of exercise and milk thistle extract with antioxidant effects and reduction of lipid peroxidation helps to improve muscle atrophy indicators in diabetic subjects. In general, according to the few studies conducted in this regard, research on the effect of sports activity and milk thistle plant extract on muscle atrophy indicators in type 2 diabetic subjects needs more research. There were also limitations in the current research, among which we can mention the lack of measurement of other indicators of oxidative damage. In summary, the results of this research showed that aerobic exercise, milk thistle plant extract and the combined intervention of aerobic exercise and milk thistle plant extract can probably be effective in the treatment of muscle atrophy caused by type 2 diabetes and the intervention of a lower dose of this plant extract can give better results. to be accompanied. Aerobic training, Tribulus extract and combined intervention aerobic training and Tribulus extract can probably be effective in treating muscle atrophy due to type 2 diabetes and lower dose intervention of this herbal extract can have better results. Diabetes leads to changes in cellular proteins, oxidative stress and disruption of the cellular defense system. It seems that the reduction of oxidative stress caused by exercise in diabetic subjects in the present study has a positive effect on the negative regulation of MuRF1 expression at the end of the exercise period. The mechanism of Atrogin-1 changes following exercise is not well defined. Therefore, the interaction of exercise and milk thistle extract with antioxidant effects and reduction of lipid peroxidation helps to improve muscle atrophy indicators in diabetic subjects. In general, according to the few studies conducted in this regard, the research on the effect of sports activity and milk thistle plant extract on muscle atrophy indicators in type 2 diabetic subjects needs more research. There were also some limitations in the current research, including the lack of measurement of other indicators of oxidative damage.