The effect of Gymnema Sylvestre supplement on the signaling pathway involved in the oxidative stress of liver tissue in ype 2 diabetic mice following aerobic training

Hassanizadeh, Reza; Jalali Dehkordi, Khosro; Taghian, Farzaneh

doi:10.48308/joeppa.2024.236344.1276

The effect of Gymnema Sylvestre supplement on the signaling pathway involved in the oxidative stress of liver tissue in ype 2 diabetic mice following aerobic training

Document Type : Original Article

Authors

Department of Physical Education and Sport Sciences, Isfahan (Khorasgan) Branch, Islamic Azad University, Isfahan, Iran

10.48308/joeppa.2024.236344.1276

Abstract

Background and Purpose: Liver disease is one of the main causes of death in diabetic patients. Type 2 diabetes is one of the most common chronic metabolic diseases and its prevalence is increasing rapidly all over the world. Liver is one of the most important organs that control blood glucose levels. Although the favorable role of Gymnema sylvester supplement and aerobic training has been reported in diabetic patients, the effect of Gymnema sylvester supplement and aerobic training on liver tissue is not well known. Therefore, the purpose of this research is the effect of Gymnema sylvester supplement on the signaling pathway involved in the oxidative stress of liver tissue in type 2 diabetic mice following aerobic training.
Materials and Methods: In this experimental research, 32 male C57BL/6 mice were randomly divided into 4 groups of eight including diabetes group and aerobic training, diabetes group and gymnema sylvester supplement, diabetes group and aerobic training with gymnema sylvester supplement and diabetes control group. Diabetic groups were made diabetic by high-fat diet for 20 weeks. Gymnema sylvester supplement groups were gavaged with 100 mg/kg daily for six weeks. Aerobic training groups performed exercise at a speed of 10 m/min on a treadmill for six weeks and five training sessions per week. Serum concentration of SOD and MDA by ELISA method and expression of Nrf2/Keap1 (nuclear factor erythroid 2–related factor 2/ Kelch-like ECH-associated protein 1) genes was measured by RT-PCR method. The data were analyzed by using SPSS and one-way analysis of variance, and Bonferroni's post-hoc test. The significance level was considered p≤0.05.
Results: Statistical analyses showed that six weeks of taking gymnema sylvester supplement, aerobic training and aerobic training with gymnema sylvester supplement caused a significant decrease in MDA and the expression of the Keap1 gene and a significant increase in SOD and the expression of the Nrf2 gene in the liver tissue (p<0.05). The greatest changes occurred in the diabetes group + aerobic training and gymnema sylvester supplement compared to diabetic control group (p<0.05). However, there were no significant differences between diabetic group and aerobic training group and gymnema supplement group (p<0.05).
Conclusion: Gymnema Sylvester supplement and aerobic training improved blood variables through reducing MDA and increasing SOD, as well as improving the signaling pathway involved in oxidative stress in liver tissue by increasing the expression of the Nrf2 gene and decreasing the expression of the Keap1 gene in type 2 diabetic mice.

Keywords

Main Subjects

biochemistry and metabolism

References

1. Qadri S, Yki-Järvinen H. Surveillance of the liver in type 2 diabetes: important but unfeasible? Diabetologia. 2024:1-13.
2. Abeysekera KW, Valenti L, Younossi Z, Dillon JF, Allen AM, Nourredin M, et al. Implementation of a liver health check in people with type 2 diabetes. The Lancet Gastroenterology & Hepatology. 2024;9(1):83-91.
3. Fan G, Zhang B, Wang J, Wang N, Qin S, Zhao W, et al. Accurate construction of NIR probe for visualizing HClO fluctuations in type I, type II diabetes and diabetic liver disease assisted by theoretical calculation. Talanta. 2024;268:125298.
4. Nogueira JP, Cusi K. Role of insulin resistance in the development of nonalcoholic fatty liver disease in people with type 2 diabetes: from bench to patient care. Diabetes Spectrum. 2024;37(1):20-8.
5. Kim K-S, Hong S, Han K, Park C-Y. Association of non-alcoholic fatty liver disease with cardiovascular disease and all cause death in patients with type 2 diabetes mellitus: nationwide population based study. bmj. 2024;384.
6. Michel M, Doll M, Albert N, Morgenstern M, Behr A, Maxeiner S, et al. Obesity and harmful alcohol consumption are predictors for advanced liver disease in the disease management program for type 2 diabetes. United European Gastroenterology Journal. 2024;12(1):11-21.
7. Oguntibeju OO. Type 2 diabetes mellitus, oxidative stress and inflammation: examining the links. International journal of physiology, pathophysiology and pharmacology. 2019;11(3):45.
8. Zhang S, Zhang S, Zhang Y, Wang H, Chen Y, Lu H. Activation of NRF2 by epiberberine improves oxidative stress and insulin resistance in T2DM mice and IR-HepG2 cells in an AMPK dependent manner. Journal of Ethnopharmacology. 2024:117931.
9. Pouresmaeil V, Al Abudi AH, Mahimid AH, Sarafraz Yazdi M, Es-Haghi A. Evaluation of serum selenium and copper levels with inflammatory cytokines and indices of oxidative stress in type 2 diabetes. Biological trace element research. 2023;201(2):617-26.
10. Yang J, Chen H, Nie Q, Huang X, Nie S. Dendrobium officinale polysaccharide ameliorates the liver metabolism disorders of type II diabetic rats. International Journal of Biological Macromolecules. 2020;164:1939-48.
11. Elekofehinti OO, Adewumi NA, Iwaloye O. Antidiabetic potential of Chromolaena Odorata leave extract and its effect on Nrf2/keap1 antioxidant pathway in the liver of diabetic-induced Wistar Rats. Advances in Traditional Medicine. 2023;23(2):513-23.
12. Memısoğullari R, Taysı S, Bakan E, Capoglu I. Antioxidant status and lipid peroxidation in type II diabetes mellitus. Cell Biochemistry and Function: Cellular biochemistry and its modulation by active agents or disease. 2003;21(3):291-6.
13. Amanat S, Ghahri S, Dianatinasab A, Fararouei M, Dianatinasab M. Exercise and type 2 diabetes. Physical Exercise for Human Health. 2020:91-105.
14. Papagianni G, Panayiotou C, Vardas M, Balaskas N, Antonopoulos C, Tachmatzidis D, et al. The anti-inflammatory effects of aerobic exercise training in patients with type 2 diabetes: A systematic review and meta-analysis. Cytokine. 2023;164:156157.
15. Ghalandari K, Shabani M, Khajehlandi A, Mohammadi A. Effect of aerobic training with silymarin consumption on glycemic indices and liver enzymes in men with type 2 diabetes. Archives of Physiology and Biochemistry. 2023;129(1):76-81.
16. Erlich AT, Tryon LD, Crilly MJ, Memme JM, Moosavi ZSM, Oliveira AN, et al. Function of specialized regulatory proteins and signaling pathways in exercise-induced muscle mitochondrial biogenesis. Integrative medicine research. 2016;5(3):187-97.
17. Hall ME, Rizwan AM, Hamid A. Cardiac Biomarkers and Exercise Training in People With Diabetes: When a Negative Is a Positive. American College of Cardiology Foundation Washington DC; 2023. p. 100193.
18. Zamani M, Ashtary‐Larky D, Nosratabadi S, Bagheri R, Wong A, Rafiei MM, et al. The effects of Gymnema Sylvestre supplementation on lipid profile, glycemic control, blood pressure, and anthropometric indices in adults: A systematic review and meta‐analysis. Phytotherapy Research. 2023;37(3):949-64.
19. Nani A, Bertuzzi F, Meneghini E, Mion E, Pintaudi B. Combined Inositols, α-Lactalbumin, Gymnema Sylvestre and Zinc Improve the Lipid Metabolic Profile of Patients with Type 2 Diabetes Mellitus: A Randomized Clinical Trial. Journal of Clinical Medicine. 2023;12(24):7650.
20. Gotteparthi S, Kotaru M, Krishnan SA, Sridevi K. Evaluation of Anti-Diabetic Activity of Zinc Oxide Nanoparticles of Gymnema sylvestre Extract on Wistar Rats. Journal of Drug Delivery and Therapeutics. 2023;13(11):31-8.
21. Al-Mosawi A. The use of Gymnema sylvestre in the treatment of diabetes: The available evidence and expert opinion. Current Clinical and Medical Education. 2024;2(02):29-31.
22. Ghosh AR, Alsayari A, Habib AH, Wahab S, Nadig AP, Rafeeq MM, et al. Anti-Tumor Potential of Gymnema sylvestre Saponin Rich Fraction on In Vitro Breast Cancer Cell Lines and In Vivo Tumor-Bearing Mouse Models. Antioxidants. 2023;12(1):134.
23. Khimmaktong W, Komolkriengkrai M, Matsathit U. Therapeutic potential of glabridin and gymnemic acid alleviates eye choroidal thickness and neovascularization in diabetic model rats. bioRxiv. 2024:2024.02. 08.579467.
24. Chen G, Xu Y, Zhang H, Muema FW, Guo M. Gymnema sylvestre extract ameliorated streptozotocin‐induced hyperglycemia in T2DM rats via gut microbiota. Food Frontiers. 2023.
25. LLabre JE, Sroga GE, Tice MJ, Vashishth D. Induction and rescue of skeletal fragility in a high-fat diet mouse model of type 2 diabetes: An in vivo and in vitro approach. Bone. 2022;156:116302.
26. Celik H, Dursun AD, Tatar Y, Omercioglu G, Bastug M. Irisin pathways in hearts of Type 1 diabetic adult male rats following 6 weeks of moderate and high-volume aerobic exercise on a treadmill. Sport Sciences for Health. 2023;19(2):597-605.
27. Kim H-J, Hong S-H, Chang S-H, Kim S, Lee AY, Jang Y, et al. Effects of feeding a diet containing Gymnema sylvestre extract: Attenuating progression of obesity in C57BL/6J mice. Asian Pacific journal of tropical medicine. 2016;9(5):437-44.
28. Piralaiy E, Rashwan Ismael B. The effect of aerobic training on SOD, GPX, TAC, and MDA in heart tissue of rats with type 2 diabetes. Journal of Applied Health Studies in Sport Physiology. 2024.
29. Hooshmand B, Attarzade Hosseini SR, Kordi MR, Davaloo T. The effect of 8-week aerobic exercise with spirulina supplementation consumption on plasma levels of MDA, SOD and TAC in men with type 2 diabetes. Sport Physiology & Management Investigations. 2019;10(4):139-48.
30. Xue X, Kuati A, Cui G. Letter to The Editor on “Effectiveness of combined aerobic and resistance exercise on cognition, metabolic health, physical function, and health-related quality of life in middle-aged and older adults with type 2 diabetes mellitus: a systematic review and meta-analysis”. Archives of physical medicine and rehabilitation. 2024.
31. Kang M-H, Lee MS, Choi M-K, Min K-S, Shibamoto T. Hypoglycemic activity of Gymnema sylvestre extracts on oxidative stress and antioxidant status in diabetic rats. Journal of agricultural and food chemistry. 2012;60(10):2517-24.
32. Laha S, Paul S. Gymnema sylvestre (Gurmar): A potent herb with anti-diabetic and antioxidant potential. Pharmacognosy Journal. 2019;11(2).
33. Hajare R. Comparing modified and relationship study of Gymnema sylvestre against diabetes. SF J Pub Health. 2018;2(2).
34. Mandal SK, Rahmat S, Sakib K, Mehjabin B, Rahman T, Rasna IJ. An Assessment of Anti-diabetic Effect of Gymnema sylvestre in Alloxan-induced Rat Model. International Research Journal of Gastroenterology and Hepatology. 2024;7(1):29-36.