Effect of resistance and endurance training with ursolic acid on oxidative stress and cognitive impairment in hippocampal tissue in HFD/STZ-induced aged diabetic rats | ||
| Iranian Journal of Basic Medical Sciences | ||
| مقاله 10، دوره 26، شماره 12، اسفند 2023، صفحه 1449-1459 اصل مقاله (524.15 K) | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22038/ijbms.2023.71230.15477 | ||
| نویسندگان | ||
| Safoura Alizade1؛ Mohammad Faramarzi* 2؛ Ebrahim Banitalebi1؛ Elham Saghaei3 | ||
| 1Department of Sport Sciences, Shahrekord University, Shahrekord, Iran | ||
| 2Department of Exercise Physiology, Faculty of Sport Sciences, University of Isfahan, Isfahan, Iran | ||
| 3Department of Pharmacology, Shahrekord University of Medical Sciences, Shahrekord, Iran | ||
| چکیده | ||
| Objective(s): The increase in age-related cognitive impairment (CIs) and diabetes mellitus is a global health concern. Exercise training has been reported to activate the Nrf2/Keap1/ARE signaling and enhance the antioxidant defense pathways in some animal models. This study aimed to investigate the effects of ursolic acid (UA) associated with resistance or endurance training on antioxidant markers, and the Nrf2/Keap1/ARE pathway in the brain of older diabetic rats. Materials and Methods: 23-month-aged diabetes induced male Wistar rats were randomly assigned to seven groups (n=8). UA supplementation (250 mg/kg, daily) was administered along with resistance (60% maximum capacity of voluntary carrying [MVCC], 14-20 climbs) or endurance training (60-75% velocity at maximal oxygen uptake [vVO2max]), five days/week for eight weeks. Cognitive-motor functioning was assessed through open-field and passive avoidance response tests. Nrf2, Keap1, and antioxidant markers including SOD, CAT, GPx, and GSH were measured in the hippocampus tissue. Results: The results showed positive effect of resistance training (P≤0.001) on Nrf2. There was endurance training with supplementation main effect (P=0.018) on Keap1 concentration. SOD revealed a significant endurance/resistance training by supplementation interaction effect (P≤0.05); however, there was no main training or UA supplementation effects on CAT, GPx, and GSH, despite improving spatial memory changes in exercise or UA groups. Conclusion: It appears that UA treatment with resistance or endurance exercise has some beneficial effects on Nrf2 and some antioxidant markers. However, more research is needed to elucidate UA’s interaction effects and exercise interventions in diabetic situations. | ||
| کلیدواژهها | ||
| Cognitive impairment؛ Diabetes؛ Hippocampus؛ Nrf2/Keap1/ARE signaling؛ Training؛ Ursolic acid | ||
| مراجع | ||
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1. Pu D, Zhao Y, Chen J, Lv A, Zhu S, Luo C, et al. Protective effects of sulforaphane on cognitive impairments and AD-like lesions in diabetic mice are associated with the upregulation of Nrf2 transcription activity. Neuroscience 2018;381:35-45. 2. Kim B, Feldman EL. Insulin resistance in the nervous system. Trends Endocrinol Metab 2012;23:133-141. 3. Sims-Robinson C, Kim B, Feldman EL. Diabetes and cognitive dysfunction. Neurobiology of Brain Disorders: Elsevier; 2015. p. 189-201. 4. Muriach M, Flores-Bellver M, Romero FJ, Barcia JM. Diabetes and the brain: Oxidative stress, inflammation, and autophagy. Oxid Med Cell Longev 2014;2014:102158-102166. 5. Zhang L, Ma Q, Zhou Y. Strawberry leaf extract treatment alleviates cognitive impairment by activating Nrf2/HO-1 signaling in rats with streptozotocin-induced diabetes. Front Aging Neurosci 2020;12:201-300. 6. Xue M, Xu W, Ou Y-N, Cao X-P, Tan M-S, Tan L, et al. Diabetes mellitus and risks of cognitive impairment and dementia: A systematic review and meta-analysis of 144 prospective studies. Ageing Res Rev 2019;55:100944. 7. Tebay LE, Robertson H, Durant ST, Vitale SR, Penning TM, Dinkova-Kostova AT, et al. Mechanisms of activation of the transcription factor Nrf2 by redox stressors, nutrient cues, and energy status and the pathways through which it attenuates degenerative disease. Free Radic Biol Med 2015;88:108-46. 8. Bryan HK, Olayanju A, Goldring CE, Park BK. The Nrf2 cell defence pathway: Keap1-dependent and-independent mechanisms of regulation. Biochem Pharmacol 2013;85:705-17. 9. Raghunath A, Sundarraj K, Nagarajan R, Arfuso F, Bian J, Kumar AP, et al. Anti-oxidant response elements: Discovery, classes, regulation and potential applications. Redox Biol 2018;17:297-314. 10. Liu Y, Deng J, Fan D. G-Rh4 improves pancreatic β-cells dysfunction in vivo and in vitro by increased expression of Nrf2 and its target genes. Food Chem Toxicol 2021;148:111925. 11. Lee KH, Cha M, Lee BH. Neuroprotective effect of anti-oxidants in the brain. Int J Mol Sci 2020;21:7152-7180. 12. Bian Y, Chen Y, Wang X, Cui G, Ung COL, Lu J-H, et al. Oxyphylla A ameliorates cognitive deficits and alleviates neuropathology via the Akt-GSK3β and Nrf2-Keap1-HO-1 pathways in vitro and in vivo murine models of Alzheimer’s disease. J Adv Res 2021;34:1-12. 13. Wang C, Wu H-m, Jing X-r, Meng Q, Liu B, Zhang H, et al. Oxidative parameters in the rat brain of chronic mild stress model for depression: relation to anhedonia-like responses. J Membr Biol 2012;245:675-681. 14. Mallard AR, Spathis JG, Coombes JS. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and exercise. Free Radic Biology Med 2020;160:471-479. 15. Cai M, Wang H, Li J-j, Zhang Y-L, Xin L, Li F, et al. The signaling mechanisms of hippocampal endoplasmic reticulum stress affecting neuronal plasticity-related protein levels in high fat diet-induced obese rats and the regulation of aerobic exercise. Brain Behav Immun 2016;57:347-359. 16. Powers SK, Jackson MJ. Exercise-induced oxidative stress: Cellular mechanisms and impact on muscle force production. Physiol Rev 2008;88:1243-1276. 17. Joseph AM, Adhihetty PJ, Leeuwenburgh C. Beneficial effects of exercise on age‐related mitochondrial dysfunction and oxidative stress in skeletal muscle. J physiol 2016;594:5105-5123. 18. Habtemariam S. Anti-oxidant and anti-inflammatory mechanisms of neuroprotection by ursolic acid: Addressing brain injury, cerebral ischemia, cognition deficit, anxiety, and depression. Oxid Med Cell Longev 2019;2019:8512048-8512065. 19. Lu J, Wu D-m, Zheng Y-l, Hu B, Cheng W, Zhang Z-f, et al. Ursolic acid improves high fat diet-induced cognitive impairments by blocking endoplasmic reticulum stress and IκB kinase β/nuclear factor-κB-mediated inflammatory pathways in mice. Brain Behav Immun 2011;25:1658-1667. 20. Alkreathy HM, Ahmad A. Catharanthus roseus combined with ursolic acid attenuates streptozotocin-induced diabetes through insulin secretion and glycogen storage. Oxid Med Cell Longev 2020;2020:8565760-586567. 21. Li L, Zhang X, Cui L, Wang L, Liu H, Ji H, et al. Ursolic acid promotes the neuroprotection by activating Nrf2 pathway after cerebral ischemia in mice. Brain Res 2013;1497:32-39. 22. Ding H, Wang H, Zhu L, Wei W. Ursolic acid ameliorates early brain injury after experimental traumatic brain injury in mice by activating the Nrf2 pathway. Neurochem Res 2017;42:337-346. 23. Qian C, Zhu C, Yu W, Jiang X, Zhang F. High-fat diet/low-dose streptozotocin-induced type 2 diabetes in rats impacts osteogenesis and Wnt signaling in bone marrow stromal cells. PLoS One 2015;10:e0136390-0136404. 24. Li S, Meng F, Liao X, Wang Y, Sun Z, Guo F, et al. Therapeutic role of ursolic acid on ameliorating hepatic steatosis and improving metabolic disorders in high-fat diet-induced non-alcoholic fatty liver disease rats. PLoS One 2014;9:e86724-86736. 25. Tófolo LP, Rinaldi W, Gôngora AB, Matiusso CCI, Pavanello A, Malta A, et al. Moderate physical training ameliorates cardiovascular dysfunction induced by high fat diet after cessation of training in adult rats. Front Physiol 2019;10:170-180. 26. Jayaprakasam B, Olson LK, Schutzki RE, Tai M-H, Nair MG. Amelioration of obesity and glucose intolerance in high-fat-fed C57BL/6 mice by anthocyanins and ursolic acid in Cornelian cherry (Cornus mas). J Agric Food Chem 2006;54:243-248. 27. Leandro C, AC Levada, SM Hirabara, R. Manhaes-de-Castro, CB De-Castro, R. Curi, and, Pithon-Curi T. Aprogram Of Moderate Physical Training For Wistar Rats Based On Maximal Oxygen Consumption. J Strength Cond Res 2007;21:751-756. 28. Shanazari Z, Farsani ZH, Faramarzi M, Banitalebi E. MyomiR-OsteomiR crosstalk induced by different modes and intensities of exercise training and its role in controlling osteogenic differentiation in old male Wistar rats. Exp Gerontol 2021;149:111305. 29. Singulani MP, Stringhetta-Garcia CT, Santos LF, Morais SRL, Louzada MJQ, Oliveira SHP, et al. Effects of strength training on osteogenic differentiation and bone strength in aging female Wistar rats. Sci Rep 2017;7:1-11. 30. Macedo AG, Krug AL, Herrera NA, Zago AS, Rush JW, Amaral SL. Low-intensity resistance training attenuates dexamethasone-induced atrophy in the flexor hallucis longus muscle. J Steroid Biochem Mol Biol 2014;143:357-364. 31. Salau VF, Erukainure OL, Ayeni G, Ibeji CU, Islam MS. Modulatory effect of ursolic acid on neurodegenerative activities in oxidative brain injury: An ex vivo study. J Food Biochem 2021;45:e13597. 32. Lin Y, Wang K, Ma C, Wang X, Gong Z, Zhang R, et al. Evaluation of metformin on cognitive improvement in patients with non-dementia vascular cognitive impairment and abnormal glucose metabolism. Front Aging Neurosci 2018;10:322. 33. Kamal M, Naz M, Jawaid T, Arif M. Natural products and their active principles used in the treatment of neurodegenerative diseases: A review. Orient Pharm Exp Med 2019;19:343-365. 34. Jang S-M, Yee S-T, Choi J, Choi M-S, Do G-M, Jeon S-M, et al. Ursolic acid enhances the cellular immune system and pancreatic β-cell function in streptozotocin-induced diabetic mice fed a high-fat diet. Int Immunopharmacol 2009;9:113-119. 35. Li W, Sun K, Hu F, Chen L, Zhang X, Wang F, et al. Protective effects of natural compounds against oxidative stress in ischemic diseases and cancers via activating the Nrf2 signaling pathway: A mini review. J Biochem Mol Toxicol 2021;35:e22658. 36. Xianchu L, Kang L, Huan P, Ming L. Ursolic acid mitigates cognitive dysfunction through amelioration of oxidative stress, inflammation and apoptosis in diabetic rats. Trop J Pharm Res 2021;20:803-807. 37. Wang X, Fang H, Xu G, Yang Y, Xu R, Liu Q, et al. Resveratrol prevents cognitive impairment in type 2 diabetic mice by upregulating Nrf2 expression and transcriptional level. Diabetes Metab Syndr Obes 2020;13:1061-1075. 38. Shih Y-H, Chein Y-C, Wang J-Y, Fu Y-S. Ursolic acid protects hippocampal neurons against kainate-induced excitotoxicity in rats. Neurosci Lett 2004;362:136-140. 39. Lu J, Zheng Y-L, Wu D-M, Luo L, Sun D-X, Shan Q. Ursolic acid ameliorates cognition deficits and attenuates oxidative damage in the brain of senescent mice induced by D-galactose. Biochem Pharmacol 2007;74:1078-1090. 40. Yoo K-Y, Park S-Y. Terpenoids as potential anti-Alzheimer’s disease therapeutics. Molecules 2012;17:3524-3538. 41. Zhang T, Su J, Wang K, Zhu T, Li X. Ursolic acid reduces oxidative stress to alleviate early brain injury following experimental subarachnoid hemorrhage. Neurosci Lett 2014;579:12-17. 42. Dumitrescu L, Popescu-Olaru I, Cozma L, Tulbă D, Hinescu ME, Ceafalan LC, et al. Oxidative stress and the microbiota-gut-brain axis. Oxid Med Cell Longev 2018;2018:2406594-2406605. 43. Shahidehpour RK, Higdon RE, Crawford NG, Neltner JH, Ighodaro ET, Patel E, et al. Dystrophic microglia are associated with neurodegenerative disease and not healthy aging in the human brain. Neurobiol Aging 2021;99:19-27. 44. Keshvari M, Rahmati M, Mirnasouri R, Chehelcheraghi F. Effects of endurance exercise and Urtica dioica on the functional, histological and molecular aspects of the hippocampus in STZ-Induced diabetic rats. J Ethnopharmacol 2020;256:112801. 45. Aksu I, Topcu A, Camsari UM, Acikgoz O. Effect of acute and chronic exercise on oxidant–anti-oxidant equilibrium in rat hippocampus, prefrontal cortex and striatum. Neurosci Lett 2009;452:281-255. 46. Zhao RR, O’Sullivan AJ, Singh MAF. Exercise or physical activity and cognitive function in adults with type 2 diabetes, insulin resistance or impaired glucose tolerance: A systematic review. Eur Rev Aging Phys Act 2018;15:1-16. 47. Baar K. Nutrition and the adaptation to endurance training. Sports Med 2014;44:5-12. 48. Dinkova-Kostova AT, Abramov AY. The emerging role of Nrf2 in mitochondrial function. Free Radic Biol Med 2015;88:179-188. 49. Iravanpour F, Dargahi L, Rezaei M, Haghani M, Heidari R, Valian N, et al. Intranasal insulin improves mitochondrial function and attenuates motor deficits in a rat 6‐OHDA model of Parkinson’s disease. CNS Neurosci Ther 2021;27:308-319. 50. Schoenfeld BJ, Contreras B, Krieger J, Grgic J, Delcastillo K, Belliard R, et al. Resistance training volume enhances muscle hypertrophy but not strength in trained men. Med Sci Sports Exerc 2019;51:94-103. 51. Rahimian R, Cordeau Jr P, Kriz J. Brain response to injuries: when microglia go sexist. Neuroscience 2019;405:14-23. 52. Camiletti-Moiron D, Aparicio V, Nebot E, Medina G, Martínez R, Kapravelou G, et al. High-intensity exercise modifies the effects of stanozolol on brain oxidative stress in rats. Int J Sports Med 2015;36:984-991. 53. Camiletti-Moirón D, Aparicio VA, Nebot E, Medina G, Martínez R, Kapravelou G, et al. High-protein diet induces oxidative stress in rat brain: Protective action of high-intensity exercise against lipid peroxidation. Nutr Hosp 2015;31:866-874. 54. da Silva Fiorin F, de Oliveira Ferreira AP, Ribeiro LR, Silva LF, de Castro MR, da Silva LR, et al. The impact of previous physical training on redox signaling after traumatic brain injury in rats: a behavioral and neurochemical approach. J Neurotrauma 2016;33:1317-1330. 55. Duan F-f, Guo Y, Li J-w, Yuan K. Antifatigue effect of luteolin-6-C-neohesperidoside on oxidative stress injury induced by forced swimming of rats through modulation of Nrf2/ARE signaling pathways. Oxid Med Cell Longev 2017;2017:3159358-315970. 56. Lappalainen Z, Lappalainen J, Oksala NK, Laaksonen DE, Khanna S, Sen CK, et al. Diabetes impairs exercise training-associated thioredoxin response and glutathione status in rat brain. J Appl Physiol 2009;106:461-467. 57. Martins RR, de Oliveira Macedo UB, Leite LD, Rezende AA, Brandão-Neto J, Almeida MdG. Lipoic acid and moderate swimming improves the estrous cycle and oxidative stress in Wistar rats. Appl Physiol Nutr Metab 2011;36:693-697. 58. Jeong J-W, Shim J-J, Choi I-D, Kim S-H, Ra J, Ku HK, et al. Apple pomace extract improves endurance in exercise performance by increasing strength and weight of skeletal muscle. J Med Food 2015;18:1380-1386. 59. Katashima CK, Silva VR, Gomes TL, Pichard C, Pimentel GD. Ursolic acid and mechanisms of actions on adipose and muscle tissue: A systematic review. Obes Rev 2017;18:700-711. 60. Kim JC, Kang YS, Noh EB, Seo BW, Seo DY, Park GD, et al. Concurrent treatment with ursolic acid and low-intensity treadmill exercise improves muscle atrophy and related outcomes in rats. Korean J Physiol Pharmacol 2018;22:427-436. | ||
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