Journal of Sport and Exercise Physiology

Journal of Sport and Exercise Physiology

Effects of six weeks of resistance training and curcumin supplementation on NF-κB, IGF-1, FOXO3a, and cata-lase expression in skeletal muscle of female rats with experimentally induced sarcopenia

Document Type : Original Article

Authors
1 Department of Exercise Physiology and Corrective Exercises, Faculty of Sport Sciences, Urmia University, Urmia, Iran
2 Department of Sports Sciences, Faculty of Humanities, University of Maragheh, Maragheh, Iran
Abstract
Background and Purpose: Sarcopenia, a major consequence of aging and sedentary lifestyle, leads to a reduced skeletal muscle function. Combining exercise interventions with anti-inflammatory compounds like curcumin may be an effective strategy to mitigate the adverse effects of sarcopenia. This study aimed to investigate the effect of six weeks of resistance training and curcumin supplementation on the protein content of NF-κB, IGF-1, FOXO3a, and catalase in the soleus muscle of female Wistar rats modeled with sarcopenia.
Materials and methods: In this experimental study, 40 female Wistar rats with an average age of 12±1 weeks were injected with dexamethasone for 10 days as an animal model of sarcopenia and randomly were divided into five groups: healthy control (C1), sarcopenic control (C2), resistance training (RT), curcumin supplementation (CS), and combined resistance training and curcumin supplementation (RTCS). The resistance training protocol involved lad-der climbing at moderate intensity (60% MVCC), three sessions per week for 6 weeks. The supplementation groups received curcumin (30 mg/kg, intraperitoneally) three times per week for 6 weeks. Soleus muscle samples were col-lected 24 hours before the intervention and immediately after the last training session. Protein levels of NF-κB, IGF-1, FOXO3a, and catalase were measured using Western blot. One-way ANOVA with Bonferroni post-hoc tests was used for data analysis.
Results: One-way ANOVA revealed significant differences in NF-κB, FOXO3a, catalase, and IGF-1 protein expres-sion among groups (p
Keywords
Subjects

1. TRASLAVIÑA Y. VEJEZ,¿ EDAD DE ORO O DE LATA? Pensamiento Republicano. 2019(11):63-80. https://doi.org/10.21017/pen.repub.2019.n11.a56 2. Amarya S, Singh K, Sabharwal M. Ageing process and physiological changes. Gerontology. 2018;32:137-44. https://doi.org/10.5772/intechopen.76249 3. Barajas-Galindo DE, Arnáiz EG, Vicente PF, Ballesteros-Pomar MD. Effects of physical exercise in sarcopenia. A systematic review. Endocrinología, Diabetes y Nutrición (English ed). 2021;68(3):159-69. https://doi.org/10.1016/j.endien.2020.02.007 4. Phu S, Vogrin S, Zanker J, Hassan EB, Al Saedi A, Duque G. Agreement between initial and revised European working group on sarcopenia in older people definitions. Journal of the American Medical Directors Association. 2019;20(3):382-3. e1. https://doi.org/10.1093/ageing/afac164 5. Chen L-Y, Wu Y-H, Liu L-K, Lee W-J, Hwang A-C, Peng L-N, et al. Association among serum insulin-like growth factor-1, frailty, muscle mass, bone mineral density, and physical performance among community-dwelling middle-aged and older adults in Taiwan. Rejuvenation Research. 2018;21(3):270-7.https://doi.org/10.3389/fendo.2024.1422472 6. Thoma A, Lightfoot AP. NF-kB and inflammatory cytokine signalling: role in skeletal muscle atrophy. Muscle Atrophy. 2018:267-79.https://doi.org/10.3390/antiox11091686 7. Sergi D, Naumovski N, Heilbronn LK, Abeywardena M, O’Callaghan N, Lionetti L, et al. Mitochondrial (dys) function and insulin resistance: from pathophysiological molecular mechanisms to the impact of diet. Frontiers in physiology. 2019;10:449821.https://doi.org/10.3389/fphys.2019.00532 8. Landi F, Calvani R, Cesari M, Tosato M, Martone AM, Ortolani E, et al. Sarcopenia: an overview on current definitions, diagnosis and treatment. Current Protein and Peptide Science. 2018;19(7):633-8.https://doi.org/10.2174/1389203718666170607113459 9. Fanzani A, Conraads VM, Penna F, Martinet W. Molecular and cellular mechanisms of skeletal muscle atrophy: an update. Journal of cachexia, sarcopenia and muscle. 2012;3:163-79. https://doi.org/10.1007/s13539-012-0074-6 10. Khaddour K, Castellanos K, Fantuzzi G, Mutlu E, Gomez-Perez SL. IGF-1 and IL-6 as predictors of sarcopenia in non-metastatic colorectal cancer patients. American Society of Clinical Oncology; 2019. https://doi.org/10.1200/JCO.2019.37.15_SUPPL.E15150 11. Tanaka K-i, Kanazawa I, Sugimoto T. Elevated serum pentosidine and decreased serum IGF-I levels are associated with loss of muscle mass in postmenopausal women with type 2 diabetes mellitus. Experimental and clinical endocrinology & diabetes. 2016;124(03):163-6.https://doi.org/10.1055/s-0035-1565103 12. Stefanetti RJ, Voisin S, Russell A, Lamon S. Recent advances in understanding the role of FOXO3. F1000Research. 2018;7:F1000 Faculty Rev-372.https://doi.org/10.12688/f1000research.15258.1 13. Urbánek P, Klotz LO. Posttranscriptional regulation of FOXO expression: microRNAs and beyond. British journal of pharmacology. 2017;174(12):1514-32.https://doi.org/10.1111/bph.13471 14. Xu H, Ranjit R, Richardson A, Van Remmen H. Muscle mitochondrial catalase expression prevents neuromuscular junction disruption, atrophy, and weakness in a mouse model of accelerated sarcopenia. Journal of Cachexia, Sarcopenia and Muscle. 2021;12(6):1582-96.https://doi.org/10.1002/jcsm.12768 15. Bellanti F, Buglio AL, Vendemiale G. Oxidative stress and sarcopenia. Aging: Elsevier; 2020. p. 95-103. https://doi.org/10.1016/j.maturitas.2017.12.002 16. Denison HJ, Cooper C, Sayer AA, Robinson SM. Prevention and optimal management of sarcopenia: a review of combined exercise and nutrition interventions to improve muscle outcomes in older people. Clinical interventions in aging. 2015:859-69.https://doi.org/10.2147/cia.s55842 17. Jiang Q, Lou K, Hou L, Lu Y, Sun L, Tan SC, et al. The effect of resistance training on serum insulin-like growth factor 1 (IGF-1): a systematic review and meta-analysis. Complementary therapies in medicine. 2020;50:102360.https://doi.org/10.1016/j.ctim.2020.102360 18. Jing Y, Zuo Y, Yu Y, Sun L, Yu Z, Ma S, et al. Single-nucleus profiling unveils a geroprotective role of the FOXO3 in primate skeletal muscle aging. Protein & Cell. 2023;14(7):499-514. https://doi.org/10.1093/procel/pwac061 19. Feng L, Li B, Xi Y, Cai M, Tian Z. Aerobic exercise and resistance exercise alleviate skeletal muscle atrophy through IGF-1/IGF-1R-PI3K/Akt pathway in mice with myocardial infarction. American Journal of Physiology-Cell Physiology. 2022;322(2):C164-C76.https://doi.org/10.1152/ajpcell.00344.2021 20. Gupta SC, Patchva S, Aggarwal BB. Therapeutic roles of curcumin: lessons learned from clinical trials. The AAPS journal. 2013;15:195-218.https://doi.org/10.1208/s12248-012-9432-8 21. Gorza L, Germinario E, Tibaudo L, Vitadello M, Tusa C, Guerra I, et al. Chronic systemic curcumin administration antagonizes murine sarcopenia and presarcopenia. International journal of molecular sciences. 2021;22(21):11789.https://doi.org/10.3390/ijms222111789 22. Tsai S-W, Huang C-C, Hsu Y-J, Chen C-J, Lee P-Y, Huang Y-H, et al. Accelerated muscle recovery after in vivo curcumin supplementation. Natural Product Communications. 2020;15(1):1934578X20901898. https://doi.org/10.1177/1934578X20901898 23. Receno CN, Liang C, Korol DL, Atalay M, Heffernan KS, Brutsaert TD, et al. Effects of prolonged dietary curcumin exposure on skeletal muscle biochemical and functional responses of aged male rats. International journal of molecular sciences. 2019;20(5):1178.https://doi.org/10.3390/ijms20051178 24. Stokes T, Hector AJ, Morton RW, McGlory C, Phillips SM. Recent perspectives regarding the role of dietary protein for the promotion of muscle hypertrophy with resistance exercise training. Nutrients. 2018;10(2):180. https://doi.org/10.3390/nu10020180 25. Christian CJ, Benian GM. Animal models of sarcopenia. Aging Cell. 2020;19(10):e13223. https://doi.org/10.1111/acel.13223 26. Daniel S, Limson JL, Dairam A, Watkins GM, Daya S. Through metal binding, curcumin protects against lead-and cadmium-induced lipid peroxidation in rat brain homogenates and against lead-induced tissue damage in rat brain. Journal of inorganic biochemistry. 2004;98(2):266-75.https://doi.org/10.1016/j.jinorgbio.2003.10.014 27. 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. The Journal of steroid biochemistry and molecular biology. 2014;143:357-64.https://doi.org/10.1016/j.jsbmb.2014.05.010 28. de Cássia Marqueti R, Almeida JA, Nakagaki WR, Guzzoni V, Boghi F, Renner A, et al. Resistance training minimizes the biomechanical effects of aging in three different rat tendons. Journal of biomechanics. 2017;53:29-35.https://doi.org/10.1016/j.jbiomech.2016.12.029 29. Cao Y, Zhou J, Quan H, Li W, Li T, Wang L. Resistance training alleviates muscle atrophy and muscle dysfunction by reducing inflammation and regulating compromised autophagy in aged skeletal muscle. Frontiers in Immunology. 2025;16:1597222.https://doi.org/10.3389/fimmu.2025.1597222 30. Papisad M, Habibi A, Shakerian S, Rami M. Comparison of the effect of resistance and continuous training on the content of PAX7, NF-KB, FOXO3 and nAChR proteins in female sarcopenia model rats. Journal of Practical Studies of Biosciences in Sport. 2025.https://doi.org/10.22077/jpsbs.2025.8286.1919 31. Vella L, Caldow MK, Larsen AE, Tassoni D, Della Gatta PA, Gran P, et al. Resistance exercise increases NF-κB activity in human skeletal muscle. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 2012;302(6):R667-R73.https://doi.org/10.1152/ajpregu.00336.2011 32. Williamson DL, Raue U, Slivka DR, Trappe S. Resistance exercise, skeletal muscle FOXO3A, and 85-year-old women. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences. 2010;65(4):335-43. https://doi.org/10.1093/gerona/glq005 33. Xue J, Han X, Zheng Y, Zhang Q, Kong L. Effectiveness of resistance training in modulating inflammatory biomarkers among Asian patients with sarcopenia: a systematic review and meta-analysis of randomized controlled trials. Frontiers in Immunology. 2024;15:1385902.https://doi.org/10.3389/fimmu.2024.1385902 34. Buhrmann C, Mobasheri A, Busch F, Aldinger C, Stahlmann R, Montaseri A, et al. Curcumin modulates nuclear factor κB (nf-κB)-mediated inflammation in human tenocytes in vitro: role of the phosphatidylinositol 3-kinase/Akt pathway. Journal of Biological Chemistry. 2011;286(32):28556-66. https://doi.org/10.1074/jbc.m111.256180 35. Saud Gany SL, Chin K-Y, Tan JK, Aminuddin A, Makpol S. Curcumin as a therapeutic agent for sarcopenia. Nutrients. 2023;15(11):2526.https://doi.org/10.3390/nu15112526 36. Lee D-Y, Chun Y-S, Kim J-K, Lee J-O, Ku S-K, Shim S-M. Curcumin attenuates sarcopenia in chronic forced exercise executed aged mice by regulating muscle degradation and protein synthesis with antioxidant and anti-inflammatory effects. Journal of Agricultural and Food Chemistry. 2021;69(22):6214-28. https://doi.org/10.1021/acs.jafc.1c00699 37. Zhang J, Zheng J, Chen H, Li X, Ye C, Zhang F, et al. Curcumin targeting NF‐κB/ubiquitin‐proteasome‐system axis ameliorates muscle atrophy in triple‐negative breast cancer cachexia mice. Mediators of Inflammation. 2022;2022(1):2567150.https://doi.org/10.1155/2022/2567150 38. McKay BR, Ogborn DI, Baker JM, Toth KG, Tarnopolsky MA, Parise G. Elevated SOCS3 and altered IL-6 signaling is associated with age-related human muscle stem cell dysfunction. American Journal of Physiology-Cell Physiology. 2013;304(8):C717-C28.https://doi.org/10.1152/ajpcell.00305.2012 39. McKay BR, Ogborn DI, Bellamy LM, Tarnopolsky MA, Parise G. Myostatin is associated with age‐related human muscle stem cell dysfunction. The FASEB Journal. 2012;26(6):2509-21. https://doi.org/10.1096/fj.11-198663 40. Midhun SJ, Arun D, Edatt L, Sruthi M, Thushara V, Oommen OV, et al. Modulation of digestive enzymes, GH, IGF-1 and IGF-2 genes in the teleost, Tilapia (Oreochromis mossambicus) by dietary curcumin. Aquaculture International. 2016;24(5):1277-86.https://doi.org/10.1007/s10499-016-9984-1 41. Ahtiainen JP, Hulmi JJ, Lehti M, Kraemer WJ, Nyman K, Selänne H, et al. Effects of resistance training on expression of IGF-I splice variants in younger and older men. European journal of sport science. 2016;16(8):1055-63.https://doi.org/10.1080/17461391.2016.1185164 42. Roberts MD, Dalbo VJ, Sunderland KL, Poole CN, Hassell SE, Bemben D, et al. IGF-1 splice variant and IGF-1 peptide expression patterns in young and old human skeletal muscle prior to and following sequential exercise bouts. European Journal of Applied Physiology. 2010;110(5):961-9. https://doi.org/10.1007/s00421-010-1588-2 43. Retamales A, Zuloaga R, Valenzuela C, Gallardo-Escarate C, Molina A, Valdés J. Insulin-like growth factor-1 suppresses the Myostatin signaling pathway during myogenic differentiation. Biochemical and biophysical research communications. 2015;464(2):596-602.https://doi.org/10.1016/j.bbrc.2015.07.018 44. Gao S, Durstine JL, Koh H-J, Carver WE, Frizzell N, Carson JA. Acute myotube protein synthesis regulation by IL-6-related cytokines. American Journal of Physiology-Cell Physiology. 2017;313(5):C487-C500. https://doi.org/10.1152/ajpcell.00112.2017 45. Firth SM, Baxter RC. Cellular actions of the insulin-like growth factor binding proteins. Endocrine reviews. 2002;23(6):824-54.https://doi.org/10.1210/er.2001-0033 46. Kuemmerle JF, Zhou H. Insulin-like growth factor-binding protein-5 (IGFBP-5) stimulates growth and IGF-I secretion in human intestinal smooth muscle by Ras-dependent activation of p38 MAP kinase and Erk1/2 pathways. Journal of Biological Chemistry. 2002;277(23):20563-71.https://doi.org/10.1074/jbc.M200885200 47. Ashrafizadeh M, Ahmadi Z, Mohammadinejad R, Farkhondeh T, Samarghandian S. Curcumin activates the Nrf2 pathway and induces cellular protection against oxidative injury. Current Molecular Medicine. 2020;20(2):116-33.https://doi.org/10.2174/1566524019666191016150757 48. Durham WJ, Arbogast S, Gerken E, Li YP, Reid MB. Progressive nuclear factor‐κB activation resistant to inhibition by contraction and curcumin in mdx mice. Muscle & Nerve: Official Journal of the American Association of Electrodiagnostic Medicine. 2006;34(3):298-303.https://doi.org/10.1002/mus.20579 49. Wang C, Bai L. Sarcopenia in the elderly: basic and clinical issues. Geriatrics & gerontology international. 2012;12(3):388-96.https://doi.org/10.1111/j.1447-0594.2012.00851 50. Seo DY, Hwang BG. Effects of exercise training on the biochemical pathways associated with sarcopenia. Physical Activity and Nutrition. 2020;24(3):32.https://doi.org/10.20463/pan.2020.0019 51. Jung W-S, Kim S-W, Kim J-W, Park H-Y. Resistance training in hypoxia as a new therapeutic modality for sarcopenia—a narrative review. Life. 2021;11(2):106.https://doi.org/10.3390/life11020106 52. Burton LA, Sumukadas D. Optimal management of sarcopenia. Clinical interventions in aging. 2010:217-28.https://doi.org/10.2147/cia.s11473 53. Chen N, He X, Feng Y, Ainsworth BE, Liu Y. Effects of resistance training in healthy older people with sarcopenia: a systematic review and meta-analysis of randomized controlled trials. European Review of Aging and Physical Activity. 2021;18(1):23.https://doi.org/10.1186/s11556-021-00277-7 54. Seo KI, Choi MS, Jung UJ, Kim HJ, Yeo J, Jeon SM, et al. Effect of curcumin supplementation on blood glucose, plasma insulin, and glucose homeostasis related enzyme activities in diabetic db/db mice. Molecular nutrition & food research. 2008;52(9):995-1004.https://doi.org/10.1002/mnfr.200700184 55. Dai C, Xiao X, Zhang Y, Xiang B, Hoyer D, Shen J, et al. Curcumin attenuates colistin-induced peripheral neurotoxicity in mice. ACS Infectious Diseases. 2020;6(4):715-24.https://doi.org/10.1021/acsinfecdis.9b00341 56. Alizadeh M, Kheirouri S. Curcumin reduces malondialdehyde and improves antioxidants in humans with diseased conditions: A comprehensive meta-analysis of randomized controlled trials. BioMedicine. 2019;9(4):23. https://doi.org/10.1051/bmdcn/2019090423

  • Receive Date 06 September 2025
  • Revise Date 04 October 2025
  • Accept Date 16 October 2025
  • First Publish Date 01 November 2025
  • Publish Date 22 June 2026