Sport Biosciences

The Interactive Effect of Six Weeks of Berberine Supplementation with Aerobic Exercise on Some Oxidative and Anti-Oxidative Indices and Caspase-3 Gene Expression in the Quadriceps Muscle of Streptozotocin-Diabetic Male Rats

Document Type : Research Paper

Authors

Azam Hamzezadeh 1
Javad Ramezani 2
Saeid Naghibi 3

1 Department of Sports Sciences, Faculty of Humanities, Payame Noor University, Karaj Center.

2 Corresponding Author, Department of Sports Sciences, Faculty of Humanities, Payame Noor University, Tehran, Iran.

3 Department of Sports Sciences, Faculty of Humanities, Payame Noor University, Tehran, Iran.

https://doi.org/10.22059/jsb.2023.363750.1602
Abstract
Introduction: Type-1 diabetes is associated with the weakness of the body's antioxidant defense and also affects skeletal muscles. This research aimed to investigate the interaction of Berberine supplementation with aerobic exercise on Malondialdehyde (MDA), Superoxide Dismutase (SOD), Glutathione Peroxidase (GPX), and also the Caspase-3 gene expression in quadriceps muscle tissue of type-1 diabetic rats.
Methods: 35 male Wistar rats were randomly divided into five groups: 1) healthy control, 2) diabetic control, 3) Berberine supplement, 4) aerobic exercise and 5) Aerobic exercise + Berberine supplement. After ensuring the induction of diabetes by STZ in the treatment groups, moderate intensity aerobic exercise was performed for six weeks with a frequency of five sessions per week according to the schedule. Berberine supplementation with a dose of 50 mg/kg was implemented by gavage on all days of the week and half an hour before exercise.
Results: The MDA and SOD levels in Berberine + aerobic exercise group significantly decreased (P<0.0019) and increased (P<0.0063), respectively compared to other groups. The level of GPX in the Berberine + aerobic exercise group had a significant increase compared to the diabetes control and aerobic exercise groups (P<0.0005 and P<0.001, respectively). Also, there was a significant increase in GPX level in the Berberine supplement group compared to the diabetes control group (P<0.0017), however, there was no significant difference between the group of Berberine + aerobic exercise and Berberine supplement (P=0.132). The Caspase-3 gene expression in Berberine + aerobic exercise group had a significant decrease compared to diabetes control and aerobic exercise groups (P<0.0001 and P<0.001, respectively). This variable also had a significant decrease in the Berberine supplement group compared to the diabetes control group (P<0.0005).
Conclusion: It seems that the simultaneous intervention of Berberine supplementation and aerobic exercise has positive synergistic effects and plays an important role in reducing MDA, caspase-3 gene expression, and increasing SOD and GPX in the quadriceps muscle of type-1 diabetic rats.

Keywords

Aerobic Exercise
Berberine
Caspase-3
Diabetic
Oxidative
Streptozotocin
Subjects

1] Anderson J, Couper JJ, Mpundu-Kaambwa C, Giles LC, Gent R, Coppin B, et al. An extra 1,000 steps per day relates to improved cardiovascular health in children with type 1 diabetes. Diabetes Care. 2016;39(8):e108–9. https://doi.org/10.2337/dc16-0526

[2] Vazeou A, Papadopoulou A, Miha M, Drakatos A, Georgacopoulos D. Cardiovascular impairment in children, adolescents, and young adults with type 1 diabetes mellitus (T1DM). Eur J Pediatr. 2008;167:877–84. https://doi.org/10.1007/s00431-007-0603-z

[3] Krause MP, Riddell MC, Hawke TJ. Effects of type 1 diabetes mellitus on skeletal muscle: clinical observations and physiological mechanisms. Pediatr Diabetes. 2011;12(4pt1):345–64. https://doi.org/10.1111/j.1399-5448.2010.00699.x

[4] Mehta MM, Weinberg SE, Chandel NS. Mitochondrial control of immunity: beyond ATP. Nat Rev Immunol. 2017;17(10):608–20. https://www.nature.com/articles/nri.2017.66

 [5] Sifuentes-Franco S, Pacheco-Moisés FP, Rodríguez-Carrizalez AD, Miranda-Díaz AG. The role of oxidative stress, mitochondrial function, and autophagy in diabetic polyneuropathy. J Diabetes Res. 2017;2017. https://doi.org/10.1155/2017/1673081

[6] Scarpulla RC. Nucleus-encoded regulators of mitochondrial function: integration of respiratory chain expression, nutrient sensing and metabolic stress. Biochim Biophys Acta (BBA)-Gene Regul Mech. 2012;1819(9–10):1088–97. https://doi.org/10.1016/j.bbagrm.2011.10.011

[7] Ibuki FK, Bergamaschi CT, da Silva Pedrosa M, Nogueira FN. Effect of vitamin C and E on oxidative stress and antioxidant system in the salivary glands of STZ-induced diabetic rats. Arch Oral Biol. 2020;116:104765. https://doi.org/10.1016/j.archoralbio.2020.104765

[8] Powers SK, Kavazis AN, McClung JM. Oxidative stress and disuse muscle atrophy. J Appl Physiol. 2007;102(6):2389–97. https://doi.org/10.1152/japplphysiol.01202.2006

[9] Sala D, Zorzano A. Differential control of muscle mass in type 1 and type 2 diabetes mellitus. Cell Mol life Sci. 2015;72:3803–17. https://doi.org/10.1007/s00018-015-1954-7

[10] Tang L, Li N, Jian W, Kang Y, Yin B, Sun S, et al. Low-intensity pulsed ultrasound prevents muscle atrophy induced by type 1 diabetes in rats. Skelet Muscle. 2017;7:1–10. https://doi.org/10.1186/s13395-017-0145-7

[11] Perry BD, Caldow MK, Brennan-Speranza TC, Sbaraglia M, Jerums G, Garnham A, et al. Muscle atrophy in patients with Type 2 Diabetes Mellitus: roles of inflammatory pathways, physical activity and exercise. Exerc Immunol Rev. 2016;22:94.

[12] Kannan K, Jain SK. Oxidative stress and apoptosis. Pathophysiology. 2000;7(3):153–63. https://doi.org/10.1016/S0928-4680(00)00053-5

[13] Yu Z, Jia Y, Chen G. Possible involvement of cathepsin B/D and caspase‐3 in deferoxamine‐related neuroprotection of early brain injury after subarachnoid haemorrhage in rats. Neuropathol Appl Neurobiol. 2014;40(3):270–83. https://doi.org/10.1111/nan.12091

[14] McClung JM, Kavazis AN, DeRuisseau KC, Falk DJ, Deering MA, Lee Y, et al. Caspase-3 regulation of diaphragm myonuclear domain during mechanical ventilation–induced atrophy. Am J Respir Crit Care Med. 2007;175(2):150–9. https://doi.org/10.1164/rccm.200601-142OC

[15] Primeau AJ, Adhihetty PJ, Hood DA. Apoptosis in heart and skeletal muscle. Can J Appl Physiol. 2002;27(4):349–95. https://doi.org/10.1139/h02-020

[16] Pal S, Chaki B, Chattopadhyay S, Bandyopadhyay A. High-intensity exercise induced oxidative stress and skeletal muscle damage in postpubertal boys and girls: A comparative study. J strength Cond Res. 2018;32(4):1045–52. https://doi: 10.1519/JSC.0000000000002167

[17] Powers SK, Deminice R, Ozdemir M, Yoshihara T, Bomkamp MP, Hyatt H. Exercise-induced oxidative stress: Friend or foe?. Journal of sport and health science. 2020 Sep 1;9(5):415-25. https://doi.org/10.1016/j.jshs.2020.04.001

[18] Margaritelis NV, Theodorou AA, Paschalis V, Veskoukis AS, Dipla K, Zafeiridis A, Panayiotou G, Vrabas IS, Kyparos A, Nikolaidis MG. Adaptations to endurance training depend on exercise‐induced oxidative stress: exploiting redox interindividual variability. Acta Physiologica. 2018 Feb;222(2):e12898. https://doi.org/10.1111/apha.12898

[19] Feinberg MJ, Lumia AR, McGinnis MY. The effect of anabolic-androgenic steroids on sexual behavior and reproductive tissues in male rats. Physiol Behav. 1997/07/01. 1997;62(1):23–30. https://doi.org/10.1016/S0031-9384(97)00105-4

[20] Møller P, Wallin H, Knudsen LE. Oxidative stress associated with exercise, psychological stress and life-style factors. Chem Biol Interact. 1996;102(1):17–36. https://doi.org/10.1016/0009-2797(96)03729-5

[21] Golbidi S, Badran M, Laher I. Antioxidant and Anti-Inflammatory Effects of Exercise in Diabetic Patients. Exp Diabetes Res. 2012;2012:1–16. https://doi.org/10.1155/2012/941868. [In persian]

[22] Ramezani J, Azarbayjani MA, Peeri M. The Aerobic Training and Berberine Chloride Intervention on Pancreatic Tissue Antioxidant Enzymes and Lipid Peroxidation in Type 1 Diabetic Rats. Iran J diabetes Obes. 2020;11(4):257–64. https://doi.org/10.18502/ijdo.v11i4.2882. [In persian]

[23] Chae CH, Jung SL, An SH, Park BY, Wang SW, Cho IH, et al. RETRACTED: Treadmill exercise improves cognitive function and facilitates nerve growth factor signaling by activating mitogen-activated protein kinase/extracellular signal-regulated kinase1/2 in the streptozotocin-induced diabetic rat hippocampus. Elsevier; 2009. https://doi.org/10.1016/j.neuroscience.2009.09.075

[24] Pan X-R, Li G-W, Hu Y-H, Wang J-X, Yang W-Y, An Z-X, et al. Effects of Diet and Exercise in Preventing NIDDM in People With Impaired Glucose Tolerance: The Da Qing IGT and Diabetes Study. Diabetes Care. 1997 Apr 1;20(4):537 LP – 544. https://doi.org/10.2337/diacare.20.4.537

[25] Yardley JE, Kenny GP, Perkins BA, Riddell MC, Balaa N, Malcolm J, et al. Resistance Versus Aerobic Exercise: Acute effects on glycemia in type 1 diabetes. Diabetes Care [Internet]. 2013 Mar 1;36(3):537–42. https://doi.org/10.2337/dc12-0963

[26] Coskun O, Ocakci A, Bayraktaroglu T, Kanter M. Exercise training prevents and protects streptozotocin-induced oxidative stress and β-cell damage in rat pancreas. Tohoku J Exp Med. 2004;203(3):145–54. https://doi.org/10.1620/tjem.203.145

[27] Yeung AWK, Orhan IE, Aggarwal BB, Battino M, Belwal T, Bishayee A, et al. Berberine, a popular dietary supplement for human and animal health: Quantitative research literature analysis a review. 2020;

[28] Vuddanda PR, Chakraborty S, Singh S. Berberine: a potential phytochemical with multispectrum therapeutic activities. Expert Opin Investig Drugs. 2010;19(10):1297–307. https://doi.org/10.1517/13543784.2010.517745

[29] Thirumalai T, Therasa SV, Elumalai EK, David E. Intense and exhaustive exercise induce oxidative stress in skeletal muscle. Asian Pacific J Trop Dis. 2011;1(1):63–6. https://doi.org/10.1016/S2222-1808(11)60016-9

[30] Alghobashy AA, Alkholy UM, Talat MA, Abdalmonem N, Zaki A, Ahmed IA, et al. Trace elements and oxidative stress in children with type 1 diabetes mellitus. Diabetes, Metab Syndr Obes. 2018;11:85–92. https://doi.org/10.2147/DMSO.S157348

[31] Landers-Ramos RQ, Jenkins NT, Spangenburg EE, Hagberg JM, Prior SJ. Circulating angiogenic and inflammatory cytokine responses to acute aerobic exercise in trained and sedentary young men. Eur J Appl Physiol. 2014;114:1377–84. https://doi.org/10.1007/s00421-014-2861-6

[32] Dede ND, Ipekci S, Kebapcilar L, Arslan M, Kurban S, Yildiz M, et al. Effect of aerobic exercise training on serum malondialdehyde level and quality of life in type 2 diabetes. In: Endocrine Abstracts. Bioscientifica; 2018. https://www.endocrine-abstracts.org/ea/0056/ea0056gp100

[33] Radak Z, Zhao Z, Koltai E, Ohno H, Atalay M. Oxygen consumption and usage during physical exercise: the balance between oxidative stress and ROS-dependent adaptive signaling. Antioxid Redox Signal. 2013;18(10):1208–46. https://doi.org/10.1089/ars.2011.4498

[34] Pereira AS, Spagnol AR, Luciano E, de Almeida Leme JAC. Influência do treinamento físico aeróbio nos marcadores séricos de estresse oxidativo em ratos diabéticos. J Phys Educ. 2016;27(1).

[35] Lima TI, Monteiro IC, Valença S, Leal-Cardoso JH, Fortunato RS, Carvalho DP, et al. Effect of exercise training on liver antioxidant enzymes in STZ-diabetic rats. Life Sci [Internet]. 2015;128:64–71. https://doi.org/10.1016/j.lfs.2015.01.031

[36] Baynes JW, Thorpe SR. The role of oxidative stress in diabetic complications. Curr Opin Endocrinol Diabetes Obes. 1996;3(4):277–84.

[37] Xie X, Chang X, Chen L, Huang K, Huang J, Wang S, et al. Berberine ameliorates experimental diabetes-induced renal inflammation and fibronectin by inhibiting the activation of RhoA/ROCK signaling. Mol Cell Endocrinol. 2013;381(1–2):56–65. https://doi.org/10.1016/j.mce.2013.07.019

[38] Wu D, Wen W, Qi C-L, Zhao R-X, Lü J-H, Zhong C-Y, et al. Ameliorative effect of berberine on renal damage in rats with diabetes induced by high-fat diet and streptozotocin. Phytomedicine. 2012;19(8–9):712–8. https://doi.org/10.1016/j.phymed.2012.03.003

[39] Maritim AC, Sanders aRA, Watkins Iii JB. Diabetes, oxidative stress, and antioxidants: a review. J Biochem Mol Toxicol. 2003;17(1):24–38. https://doi.org/10.1002/jbt.10058

[40] Wang Y, Campbell T, Perry B, Beaurepaire C, Qin L. Hypoglycemic and insulin-sensitizing effects of berberine in high-fat diet-and streptozotocin-induced diabetic rats. Metabolism. 2011;60(2):298–305. https://doi.org/10.1016/j.metabol.2010.02.005

[41] Chatuphonprasert W, Lao-Ong T, Jarukamjorn K. Improvement of superoxide dismutase and catalase in streptozotocin–nicotinamide-induced type 2-diabetes in mice by berberine and glibenclamide. Pharm Biol. 2014;52(4):419–27. https://doi.org/10.3109/13880209.2013.839714

[42] Zhu X, Guo X, Mao G, Gao Z, Wang H, He Q, et al. Hepatoprotection of Berberine Against Hydrogen Peroxide‐induced Apoptosis by Upregulation of Sirtuin 1. Phyther Res. 2013;27(3):417–21. https://doi.org/10.1002/ptr.4728

[43] van der Horst A, Tertoolen LGJ, de Vries-Smits LMM, Frye RA, Medema RH, Burgering BMT. FOXO4 is acetylated upon peroxide stress and deacetylated by the longevity protein hSir2SIRT1. J Biol Chem. 2004;279(28):28873–9. https://doi.org/10.1074/jbc.M401138200

[44] Wang Q, Zhang M, Liang B, Shirwany N, Zhu Y, Zou M-H. Activation of AMP-activated protein kinase is required for berberine-induced reduction of atherosclerosis in mice: the role of uncoupling protein 2. PLoS One. 2011;6(9):e25436. https://doi.org/10.1371/journal.pone.0025436

[45] Gao Y, Ordas R, Klein JD, Price SR. Regulation of caspase-3 activity by insulin in skeletal muscle cells involves both PI3-kinase and MEK-1/2. J Appl Physiol. 2008;105(6):1772–8. https://doi.org/10.1152/japplphysiol.90636.2008

[46] Leeuwenburgh C. Role of apoptosis in sarcopenia. Journals Gerontol Ser A Biol Sci Med Sci. 2003;58(11):M999–1001. https://doi.org/10.1093/gerona/58.11.M999

[47] Phillips T, Leeuwenburgh C. Muscle fiber‐specific apoptosis and TNF‐α signaling in sarcopenia are attenuated by life‐long calorie restriction. FASEB J. 2005;19(6):1–33. https://doi.org/10.1096/fj.04-2870fje

[48] Payne AM, Dodd SL, Leeuwenburgh C. Life-long calorie restriction in Fischer 344 rats attenuates age-related loss in skeletal muscle-specific force and reduces extracellular space. J Appl Physiol. 2003;95(6):2554–62. https://doi.org/10.1152/japplphysiol.00758.2003

[49] Hengartner MO. The biochemistry of apoptosis. Nature. 2000;407(6805):770–6. https://doi.org/10.1038/35037710

[50] Chueh WH, Lin JY. Berberine, an isoquinoline alkaloid, inhibits streptozotocin-induced apoptosis in mouse pancreatic islets through down-regulating Bax/Bcl-2 gene expression ratio. Food Chem [Internet]. 2012;132(1):252–60. https://doi.org/10.1016/j.foodchem.2011.10.065

  • Receive Date 23 August 2023
  • Revise Date 05 November 2023
  • Accept Date 18 November 2023

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