Document Type : Research Paper I Open Access I Released under CC BY-NC 4.0 license


1 Department of Physical Education and Sport Sciences, Islamic Azad University, Sanandaj Branch, Sanandaj, Iran

2 . Corresponding Author Department of Physical Education and Sports Sciences, Faculty of Humanities, Sanandaj Branch, Islamic Azad University, Sanandaj, Iran.

3 Department of Biochemistry, Bushehr University of Medical Sciences, Bushehr, Iran.

4 Department of Laboratory Hematology and Blood Bank, Bushehr University of Medical Sciences, Bushehr, Iran.

5 Department of Medical Mycology, Bushehr University of Medical Sciences, Bushehr, Iran


Introduction: Sports activity and Urtica Dioica extract consumption increase the expression of genes involved in the conversion of white to brown adipose tissue, but their combined effect is not yet clear. This study aimed to investigate the effect of Urtica dioica extract consumption and aerobic training on serum Irisin and FGF21 concentration and PGC-1α and UCP1 gene expression in diabetic obese rats.
Methods: In an experimental design, Seventy male Wistar rats (mean weight: 227.35± 18.52 grams) were randomly divided into seven Healthy Control, Diabetic Control, Urtica Dioica, Metformin, Training, Urtica Dioica + Training, and Metformin + Training groups. The Training groups performed forced swimming training for four weeks, five days per week, and each day from 15 minutes (in the first week) to 50 minutes (in the fourth week). Each day, Urtica Dioica and Metformin groups received 1.25 and 100 mg/kg of these two substances, respectively via gavage. After the end of the intervention, rats’ blood samples, posterior thigh muscle tissues, pancreas, and fat (visceral) were taken to check the research variables. One-way analysis of variance and Bonferroni's post hoc test with a significance level of 0.05 was used to analyze the data.
Results: The serum Irisin concentration of the Metformin + exercise group was significantly higher than the Diabetic Control group (P<0.05). No significant difference was observed in the serum FGF21 concentration of all groups. A significant increase in PGC-1α and UCP-1 gene expression was observed in all treatment groups compared to Healthy Control and Diabetic Control groups (P<0.05).
Conclusion: The simultaneous consumption of Urtica Dioica extract and swimming training reduces blood glucose and also activates the PGC-1α and UCP-1 gene expression, which play a role in adipose tissue browning.


Main Subjects

  1. Rayapu L, Chakraborty K, Valluru L. Marine Algae as a Potential Source for Anti-diabetic Compounds - A Brief Review. Current Pharmaceutical Design. 2021;27(6):789-801.
  2. Bowden Davies KA, Sprung VS, Norman JA, Thompson A, Mitchell KL, Halford JCG, et al. Short-term decreased physical activity with increased sedentary behaviour causes metabolic derangements and altered body composition: effects in individuals with and without a first-degree relative with type 2 diabetes. Diabetologia. 2018;61(6):1282-94.
  3. Montanari T, Pošćić N, Colitti M. Factors involved in white‐to‐brown adipose tissue conversion and in thermogenesis: a review. Obesity Reviews. 2017;18(5):495-513.
  4. Senthivinayagam S, Serbulea V, Upchurch CM, Polanowska-Grabowska R, Mendu SK, Sahu S, et al. Adaptive thermogenesis in brown adipose tissue involves activation of pannexin-1 channels. Molecular Metabolism. 2021;44:101130.
  5. van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, Drossaerts JM, Kemerink GJ, Bouvy ND, et al. Cold-activated brown adipose tissue in healthy men. New England Journal of Medicine. 2009;360(15):1500-8.
  6. El Hadi H, Di Vincenzo A, Vettor R, Rossato M. Food Ingredients Involved in White-to-Brown Adipose Tissue Conversion and in Calorie Burning. Frontiers in Physiology. 2019;9.
  7. Handschin C, Spiegelman BM. The role of exercise and PGC1α in inflammation and chronic disease. Nature. 2008;454(7203):463-9.
  8. De Sousa RAL. Brief report of the effects of the aerobic, resistance, and high-intensity interval training in type 2 diabetes mellitus individuals. International Journal of Diabetes in Developing Countries. 2018;38(2):138-45.
  9. Tentolouris A, Eleftheriadou I, Tsilingiris D, Anastasiou IA, Kosta OA, Mourouzis I, et al. Plasma Irisin Levels in Subjects with Type 1 Diabetes: Comparison with Healthy Controls. Horm Metab Res. 2018;50(11):803-10.
  10. Ritchie M, Hanouneh IA, Noureddin M, Rolph T, Alkhouri N. Fibroblast growth factor (FGF)-21 based therapies: A magic bullet for nonalcoholic fatty liver disease (NAFLD)? Expert Opinion on Investigational Drugs. 2020;29(2):197-204.
  11. Zouhar P, Janovska P, Stanic S, Bardova K, Funda J, Haberlova B, et al. A pyrexic effect of FGF21 independent of energy expenditure and UCP1. Molecular Metabolism. 2021;53:101324.
  12. Severinsen MCK, Schéele C, Pedersen BK. Exercise and browning of white adipose tissue–a translational perspective. Current Opinion in Pharmacology. 2020;52:18-24.
  13. Kleiner S, Douris N, Fox EC, Mepani RJ, Verdeguer F, Wu J, et al. FGF21 regulates PGC-1α and browning of white adipose tissues in adaptive thermogenesis. Genes & development. 2012;26(3):271-81.
  14. Jaffari H, Abedi B, Fatolahi H. The Effect of 8 Weeks of Carob Supplementation and Resistance Training on Lipid Profile and Irisin in Obese Men. 20.
  15. Sutherland LN, Bomhof MR, Capozzi LC, Basaraba SAU, Wright DC. Exercise and adrenaline increase PGC- 1α mRNA expression in rat adipose tissue. J Physiol,2009; 587, 1607–1617.
  16. Norheim F, Langleite TM, Hjorth M, Holen T, Kielland A, Stadheim HK, et al. Drevon, C. The effects of acute and chronic exercise on PGC-1α, irisin and browning of subcutaneous adipose tissue in humans. FEBS Journal, 2014; 281(3), 739-49.
  17. Mathieu C. Can we reduce hypoglycaemia with insulin detemir? International Journal of Obesity. 2004;28(2):S35-S40.
  18. Alarcón-Aguilar F, Lara-Lemus A, Flores-Saenz J. Hypoglycemic effect of plants used in Mexico as antidiabetics. Archives of medical research. 1992;23(1):59-64.
  19. Dadvar N, Ghalavand A, Zakerkish M, Hojat S, Alijani E, Mahmoodkhanikooshkaki R. The effect of aerobic training and Urtica Dioica on lipid profile and fasting blood glucose in middle age female with type II diabetes. Iran J Med Sci 2017; 15(6): 507-16. [in Persian]
  20. Oliaee D, Niazkar HR, Abbasnezhad A, Ghorbani M, Alavi Shahri PS, Saghaee Shahri S, et al. The Effects of Medicinal Plants on Pancreatic Beta Cells in Diabetes: A Systematic Review of Iranians’ Contributions. Reviews in Clinical Medicine. 2020;7(1):30-6.
  21. Khouri V, Gholalipour M. Chronic effect of the hydroalcholic extract of Urtica dioica leaves in regeneration of β-cells of hyperglycemic STZ rats. Journal of Medicinal Plants. 2006;5(17):23-30. In persian
  22. Nickavar B, Yousefian N. Evaluation of α-amylase inhibitory activities of selected antidiabetic medicinal plants. Journal für Verbraucherschutz und Lebensmittelsicherheit. 2011;6(2):191-5.
  23. Domola MS, Vu V, Robson‐Doucette CA, Sweeney G, Wheeler MB. Insulin mimetics in Urtica dioica: structural and computational analyses of Urtica dioica extracts. Phytotherapy research. 2010;24(S2):S175-S82.
  24. Ranjbari A, Azarbayjani MA, Yusof A, Halim Mokhtar A, Akbarzadeh S, Ibrahim MY, et al. In vivo and in vitro evaluation of the effects of Urtica dioica and swimming activity on diabetic factors and pancreatic beta cells. BMC complementary and alternative medicine. 2016;16(1):1-11.

25, Sarani Maram Y, Vahidian Rezazadeh, Fanai, Hamed. The training effect of resistance, endurance exercises and consumption of nettle extract on plasma apelin and weight change in type 1 rats. Applied studies of biological sciences in sports. 2020 September 22; 8 (16): 72-84. In persian

  1. Gohari A, Noorafshan A, Akmali M, Zamani-Garmsiri F, Seghatoleslam A. Urtica dioica distillate regenerates pancreatic beta cells in streptozotocin-induced diabetic rats. Iranian journal of medical sciences. 2018;43(2):174.
  2. Wrann CD, White JP, Salogiannnis J, Laznik-Bogoslavski D, Wu J, Ma D, et al. Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway. Cell metabolism. 2013;18(5):649-59.

28.King GL. The role of inflammatory cytokines in diabetes and its complications. Journal of periodontology. 2008 Aug;79:1527-34.

  1. Otero-Díaz B, Rodríguez-Flores M, Sánchez-Muñoz V, Monraz-Preciado F, Ordoñez-Ortega S, Becerril-Elias V, et al. Exercise induces white adipose tissue browning across the weight spectrum in humans. Frontiers in physiology. 2018;9:1781.
  2. Boström P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012;481(7382):463-8.
  3. Reisi J, Rajabi H, Ghaedi K, Marandi S-M, Dehkhoda M-R. Effect of Acute Resistance Training on Plasma Irisin Protein Level and Expression of Muscle FNDC5 and Adipose Tissue UCP1 Genes in Male Rats. Journal of Isfahan Medical School. 2013;31(256):1657-66.
  4. Ghaderi M, Mohebbi H, Soltani B. The effect of 14 weeks of endurance training with two different Intensity on serum irisin level, gene expression of skeletal muscle PGC1-α and FNDC5 and subcutaneous adipose tissue UCP1 in obese rats. Medical Journal of Tabriz University of Medical Sciences. 2019;41(1):72-81. In persian
  5. Timmons JA, Baar K, Davidsen PK, Atherton PJ. Is irisin a human exercise gene? Nature. 2012;488(7413):E9-E10.
  6. Pekkala S, Wiklund PK, Hulmi JJ, Ahtiainen JP, Horttanainen M, Pöllänen E, et al. Are skeletal muscle FNDC5 gene expression and irisin release regulated by exercise and related to health? The Journal of physiology. 2013;591(21):5393-400.
  7. Nygaard H, Slettaløkken G, Vegge G, Hollan I, Whist JE, Strand T, et al. Irisin in blood increases transiently after single sessions of intense endurance exercise and heavy strength training. PloS one. 2015;10(3):e0121367.
  8. Kim KH, Kim SH, Min Y-K, Yang H-M, Lee J-B, Lee M-S. Acute exercise induces FGF21 expression in mice and in healthy humans. PloS one. 2013;8(5):e63517.
  9. Namazi N, Tarighat Esfanjani A, Avari M, Heshmati J. Effects of Hydroalcoholic Nettle Extract on Insulin Sensitivity and Some Inflammatory Indicator in type 2 Diabetic Patients. Avicenna J Clin Med 2012; 18 (4) :10-14
  10. Ranjbari A, Salamat KM, Akbarzadeh S, Khamisipour G. The effect of consumption of aqueous extract of nettle plant along with endurance exercise on CRP concentration, blood glucose, weight, and changes in pancreas, liver and heart tissues of STZ-treated diabetic rats. Journal of knowledge and health in basic medical sciences. 2019 Mar 17:17-26. In persian