Skip to main content

Protective effects of saffron extract and resistance training against atrophic markers: a study on rats with dexamethasone-induced muscle atrophy

Abstract

Objectives

Multiple physiopathological conditions through stimulate atrogene led to trigger skeletal muscle atrophy, which the regulation of this signaling pathway is still not fully understood. In this study, researchers evaluated the assumptions that saffron extract and resistance training may inhibit muscle atrophy and Atrogene expression, increase testosterone concentration as well as weight in rats with dexamethasone (dex)-induced muscle atrophy.

Study design

We evaluated the effects of saffron extract and resistance training on atrophic markers in rats with dex-induced muscle atrophy using seven experimental groups.

Methods

42 male SD (Sprague-Dawley) rats were randomly distributed into seven subgroups: (1) dex-control (cn), (2) dex-resistance training (tn), (3) dex-saffron feeding 20 mg/kg/day (sa 20 mg), (4) dex-saffron feeding 40 mg/kg/day (sa 40 mg), (5) dex-saffron feeding 20 mg/kg/day + resistance training (sa 20 mg + tn), (6) dex-saffron feeding 40 mg/kg/day + resistance training (sa 40 mg + tn), and (7) healthy control i.e. non-injected dex (cn-i). order to induce muscle atrophy, groups 1 to 6 were intraperitoneally injected with dexamethasone (750 μg/kg). The resistance training protocol and 20 and 40 mg/kg/day saffron treatments were carried out for 2 months.

Results

Total weight, soleus, and EDL muscles weight in dex + 20 and 40 mg Saffron, resistance training, resistance training + 20, and 40 mg Saffron groups were significantly increased compared to pre-experimental levels or the health control group (P < 0.05). The serum testosterone level was significantly increased in resistance training + 20 and 40 mg Saffron groups compared to the health control group (P < 0.05). The level of Atrogin-1, Murf-1, and Mir-29b gene expressions in soleus and EDL muscles was significantly elevated in resistance training + 20 and 40 mg Saffron groups compared to the health control group (P < 0.05).

Conclusion

These findings set saffron alongside resistance exercise as a new target in therapeutic approaches toward clinical conditions causing muscle mass loss.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

References

  1. Ninfali C et al (2018) Regulation of muscle atrophy-related genes by the opposing transcriptional activities of ZEB1/CtBP and FOXO3. Nucleic Acids Res 46(20):10697–10708

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Lecker SH et al (1999) Muscle protein breakdown and the critical role of the ubiquitin-proteasome pathway in normal and disease states. J Nutr 129(1):227S-237S

    Article  CAS  PubMed  Google Scholar 

  3. Milan G et al (2015) Regulation of autophagy and the ubiquitin–proteasome system by the FoxO transcriptional network during muscle atrophy. Nat Commun 6:6670

    Article  CAS  PubMed  Google Scholar 

  4. Sacheck JM et al (2007) Rapid disuse and denervation atrophy involve transcriptional changes similar to those of muscle wasting during systemic diseases. FASEB J 21(1):140–155

    Article  CAS  PubMed  Google Scholar 

  5. Lecker SH et al (2004) Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression. FASEB J 18(1):39–51

    Article  CAS  PubMed  Google Scholar 

  6. Centner T et al (2001) Identification of muscle specific ring finger proteins as potential regulators of the titin kinase domain. J Mol Biol 306(4):717–726

    Article  CAS  PubMed  Google Scholar 

  7. Bodine SC et al (2001) Identification of ubiquitin ligases required for skeletal muscle atrophy. Science 294(5547):1704–1708

    Article  CAS  PubMed  Google Scholar 

  8. Glass D, Roubenoff R (2010) Recent advances in the biology and therapy of muscle wasting. Ann N Y Acad Sci 1211(1):25–36

    Article  PubMed  Google Scholar 

  9. Kedar V et al (2004) Muscle-specific RING finger 1 is a bona fide ubiquitin ligase that degrades cardiac troponin I. Proc Natl Acad Sci 101(52):18135–18140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Li J et al (2017) miR-29b contributes to multiple types of muscle atrophy. Nat Commun 8:15201

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Schroeder ET et al (2013) Are acute post-resistance exercise increases in testosterone, growth hormone, and IGF-1 necessary to stimulate skeletal muscle anabolism and hypertrophy? Med Sci Sports Exerc 45(11):2044–2051

    Article  PubMed  Google Scholar 

  12. Baehr LM et al (2017) Muscle-specific and age-related changes in protein synthesis and protein degradation in response to hindlimb unloading in rats. J Appl Physiol 122(5):1336–1350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Marzetti E et al (2008) Age-related activation of mitochondrial caspase-independent apoptotic signaling in rat gastrocnemius muscle. Mech Ageing Dev 129(9):542–549

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Su J et al (2015) A novel atlas of gene expression in human skeletal muscle reveals molecular changes associated with aging. Skelet Muscle 5(1):35

    Article  PubMed  PubMed Central  Google Scholar 

  15. Gao Y et al (2018) One-pot synthesis of 3-functionalized 4-hydroxycoumarin under catalyst-free conditions. Molecules 23(1):235

    Article  PubMed  PubMed Central  Google Scholar 

  16. Magne H et al (2013) Nutritional strategies to counteract muscle atrophy caused by disuse and to improve recovery. Nutr Res Rev 26(2):149–165

    Article  CAS  PubMed  Google Scholar 

  17. Wiggs MP (2015) Can endurance exercise preconditioning prevention disuse muscle atrophy? Front Physiol 6:63

    Article  PubMed  PubMed Central  Google Scholar 

  18. Bodine SC (2013) Disuse-induced muscle wasting. Int J Biochem Cell Biol 45(10):2200–2208

    Article  CAS  PubMed  Google Scholar 

  19. Fujino H et al (2009) Protective effects of exercise preconditioning on hindlimb unloading-induced atrophy of rat soleus muscle. Acta Physiol 197(1):65–74

    Article  CAS  Google Scholar 

  20. Schoenfeld BJ et al (2016) Muscular adaptations in low-versus high-load resistance training: a meta-analysis. Eur J Sport Sci 16(1):1–10

    Article  PubMed  Google Scholar 

  21. McGlory C, Phillips SM (2015) Exercise and the regulation of skeletal muscle hypertrophy. Progress in molecular biology and translational science. Elsevier, Amsterdam, pp 153–173

    Google Scholar 

  22. McLeod M et al (2016) Live strong and prosper: the importance of skeletal muscle strength for healthy ageing. Biogerontology 17(3):497–510

    Article  PubMed  PubMed Central  Google Scholar 

  23. Tung NH, Shoyama Y (2013) New minor glycoside components from saffron. J Nat Med 67(3):672–676

    Article  PubMed  Google Scholar 

  24. Bhattacharjee B et al (2012) Comparative reverse screening approach to identify potential anti-neoplastic targets of saffron functional components and binding mode. Asian Pac J Cancer Prev 13(11):5605–5611

    Article  PubMed  Google Scholar 

  25. Asai A et al (2005) Orally administered crocetin and crocins are absorbed into blood plasma as crocetin and its glucuronide conjugates in mice. J Agric Food Chem 53(18):7302–7306

    Article  CAS  PubMed  Google Scholar 

  26. Yang L et al (2010) Inhibitory effect on protein kinase Cθ by Crocetin attenuates palmitate-induced insulin insensitivity in 3T3-L1 adipocytes. Eur J Pharmacol 642(1):47–55

    Article  CAS  PubMed  Google Scholar 

  27. Xi L et al (2007) Beneficial impact of crocetin, a carotenoid from saffron, on insulin sensitivity in fructose-fed rats. J Nutr Biochem 18(1):64–72

    Article  CAS  PubMed  Google Scholar 

  28. Srivastava R et al (2010) Crocus sativus L.: a comprehensive review. Pharmacogn Rev 4(8):200–208

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Bathaie SZ, Mousavi SZ (2010) New applications and mechanisms of action of saffron and its important ingredients. Crit Rev Food Sci Nutr 50(8):761–786

    Article  CAS  PubMed  Google Scholar 

  30. Abdullaev FI (1993) Biological effects of saffron. BioFactors (Oxford, England) 4(2):83–86

    CAS  PubMed  Google Scholar 

  31. Feizzadeh B et al (2008) Cytotoxic effect of saffron stigma aqueous extract on human transitional cell carcinoma and mouse fibroblast. Urol J 5(3):161–167

    PubMed  Google Scholar 

  32. Abdullaev F, Espinosa-Aguirre J (2004) Biomedical properties of saffron and its potential use in cancer therapy and chemoprevention trials. Cancer Detect Prev 28(6):426–432

    Article  CAS  PubMed  Google Scholar 

  33. Schmidt M, Betti G, Hensel A (2007) Saffron in phytotherapy: pharmacology and clinical uses. Wien Med Wochenschr 157(13–14):315

    Article  PubMed  Google Scholar 

  34. Howes M-JR, Perry E (2011) The role of phytochemicals in the treatment and prevention of dementia. Drugs Aging 28(6):439–468

    Article  CAS  PubMed  Google Scholar 

  35. Zheng YQ et al (2010) Effects and mechanism of Weinaokang on reperfusion-induced vascular injury to cerebral microvessels after global cerebral ischemia. Chin J Integr Med 16(2):145–150

    Article  PubMed  Google Scholar 

  36. Mashmoul M et al (2016) Protective effects of saffron extract and crocin supplementation on fatty liver tissue of high-fat diet-induced obese rats. BMC Complement Altern Med 16(1):401

    Article  PubMed  PubMed Central  Google Scholar 

  37. Minet-Quinard R et al (2000) Induction of a catabolic state in rats by dexamethasone: dose or time dependency? J Parenter Enter Nutr 24(1):30–36

    Article  CAS  Google Scholar 

  38. Dehghan F et al (2016) Saffron with resistance exercise improves diabetic parameters through the GLUT4/AMPK pathway in-vitro and in-vivo. Sci Rep 6:25139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Leite RD et al (2009) Effects of ovariectomy and resistance training on lipid content in skeletal muscle, liver, and heart; fat depots; and lipid profile. Appl Physiol Nutr Metab 34(6):1079–1086

    Article  PubMed  Google Scholar 

  40. Wolfe RR (2006) The underappreciated role of muscle in health and disease. Am J Clin Nutr 84(3):475–482

    Article  CAS  PubMed  Google Scholar 

  41. Ruiz JR et al (2008) Association between muscular strength and mortality in men: prospective cohort study. BMJ 337:a439

    Article  PubMed  Google Scholar 

  42. Inoue T et al (2020) Undernutrition, sarcopenia, and frailty in fragility hip fracture: advanced strategies for improving clinical outcomes. Nutrients 12(12):3743

    Article  PubMed  PubMed Central  Google Scholar 

  43. Turati M et al (2020) What’s new about etiopathogenesis of musculoskeletal injuries in adolescent athletes? Minerva Pediatr. https://doi.org/10.23736/S0026-4946.20.05944-7

    Article  Google Scholar 

  44. Mohajeri D et al (2008) Anti-diabetic activity of Crocus sativus L. (Saffron) stigma ethanolic extract in alloxan-induced diabetic rats. Res J Biol Sci 3(9):1102–1108

    Google Scholar 

  45. Elgazar AF, Rezq AA, Bukhari HM (2013) Anti-hyperglycemic effect of saffron extract in alloxan-induced diabetic rats. Eur J Biol Sci 5(1):14–22

    Google Scholar 

  46. Kianbakht S, Hajiaghaee R (2011) Anti-hyperglycemic effects of saffron and its active constituents, crocin and safranal, in alloxan-induced diabetic rats. J Med Plants 3(39):82–89

    Google Scholar 

  47. Miller T et al (2018) Resistance training combined with diet decreases body fat while preserving lean mass independent of resting metabolic rate: a randomized trial. Int J Sport Nutr Exerc Metab 28(1):46

    Article  CAS  PubMed  Google Scholar 

  48. Nahid K et al (2009) The effect of an Iranian herbal drug on primary dysmenorrhea: a clinical controlled trial. J Midwifery Womens Health 54(5):401–404

    Article  PubMed  Google Scholar 

  49. Modaresi M et al (2008) Effect of Saffron (Crocus sativus) extract on level of FSH, LH and testosterone in mice. J Adv Med Biomed Res 16(63):11–18

    Google Scholar 

  50. Vaez A, Mardani M, Razavi S (2014) Impact of saffron on rat sperm membrane integrity and spermatogenesis status. Adv Biomed Res 3:146–146

    PubMed  PubMed Central  Google Scholar 

  51. Marin D, Junior A (2007) Responses of serum testosterone and triiodothyronine after intense resistance training. R Bras Ci e Mov 15(4):31–38

    Google Scholar 

  52. Raastad T, Bjøro T, Hallen J (2000) Hormonal responses to high-and moderate-intensity strength exercise. Eur J Appl Physiol 82(1–2):121–128

    Article  CAS  PubMed  Google Scholar 

  53. Kraemer WJ et al (1991) Endogenous anabolic hormonal and growth factor responses to heavy resistance exercise in males and females. Int J Sports Med 12(02):228–235

    Article  CAS  PubMed  Google Scholar 

  54. Miyazaki M et al (2011) Early activation of mTORC1 signalling in response to mechanical overload is independent of phosphoinositide 3-kinase/Akt signalling. J Physiol 589(7):1831–1846

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Bickel CS et al (2005) Time course of molecular responses of human skeletal muscle to acute bouts of resistance exercise. J Appl Physiol 98(2):482–488

    Article  CAS  PubMed  Google Scholar 

  56. Goodman CA et al (2011) Novel insights into the regulation of skeletal muscle protein synthesis as revealed by a new nonradioactive in vivo technique. FASEB J 25(3):1028–1039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Snijders T et al (2015) Satellite cells in human skeletal muscle plasticity. Front Physiol 6:283

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Firouzeh Dehghan.

Ethics declarations

Conflict of interest

The authors declare to have no conflicts of interest.

Ethical approval and funding

Animal experiments were approved at Islamic Azad University, North branch with ethics number 227/2018/36 for the care and use of laboratory animals. The authors have no funding to report.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Dehghan, F., Amiri, F. & Amiri, F. Protective effects of saffron extract and resistance training against atrophic markers: a study on rats with dexamethasone-induced muscle atrophy. Sport Sci Health 19, 85–94 (2023). https://doi.org/10.1007/s11332-022-01002-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11332-022-01002-2

Keywords

  • Muscle mass loss
  • Saffron
  • Resistance exercise
  • Atrophic markers