Skip to content
2000
image of Ginsenoside Rg1 Attenuates Muscle Atrophy in Hyperglycemic Conditions, Inactivity and Protein Deprivation Models via AKT/mTOR Pathway Activation
file format pdf download PDF

Abstract

Background

Muscle atrophy, a debilitating condition prevalent in diabetes and extended periods of immobilization, lacks robust therapeutic strategies. This investigation examines ginsenoside Rg1's therapeutic potential in counteracting muscle atrophy under hyperglycemic conditions and in experimental models of immobilization and dietary protein restriction.

Methods

C2C12 murine myoblasts were cultured under variable glucose concentrations and treated with or without Rg1. Multiple cellular parameters were evaluated, including cell viability, apoptotic indices, cell cycle distribution, and protein synthesis rates. The activation status of the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling cascade and expression of atrophy-related markers were quantified using qRT-PCR and Western blot analyses. In parallel animal studies, rats were subjected to either immobilization or protein restriction protocols, with or without Rg1 administration. Muscle function, mass, and relevant biomarkers were evaluated.

Results

Hyperglycemic conditions significantly compromised C2C12 myoblast viability, triggered apoptotic pathways, and disrupted normal cell cycle progression. Rg1 administration effectively attenuated these detrimental effects through enhanced AKT/mTOR pathway activation, upregulation of Myogenin (MyoG) expression, and suppression of atrophy-associated markers. In the rat models, Rg1 supplementation significantly ameliorated muscle deterioration, maintaining muscle mass, contractile force, and exercise tolerance, while simultaneously modulating atrophy signaling pathways and attenuating inflammatory responses. The protective effects of Rg1 were abrogated after the co-treatment with an AKT inhibitor.

Conclusion

Ginsenoside Rg1 exhibits significant protective properties against muscle atrophy under hyperglycemic conditions and in experimental models of immobilization and protein restriction, primarily mediated through activation of the AKT/mTOR signaling pathway. These findings establish Rg1 as a promising therapeutic candidate for the treatment of muscle atrophy.

2025 © 2025 The Author(s). Published by Bentham Science Publisher.
This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Loading

Article metrics loading...

/content/journals/cmm/10.2174/0115665240355315250414051525
2025-04-23
2025-09-14

  • From This Site

    /content/journals/cmm/10.2174/0115665240355315250414051525
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

/deliver/fulltext/cmm/10.2174/0115665240355315250414051525/BMS-CMM-2024-353.html?itemId=/content/journals/cmm/10.2174/0115665240355315250414051525&mimeType=html&fmt=ahah

References

  1. Larsson L. Degens H. Li M. Salviati L. Lee Y. Thompson W. Kirkland J.L. Sandri M. Sarcopenia: Aging-related loss of muscle mass and function. Physiol. Rev. 2019 99 1 427 511 10.1152/physrev.00061.2017 30427277
    [Google Scholar]
  2. Wiedmer P. Jung T. Castro J.P. Pomatto L.C.D. Sun P.Y. Davies K.J.A. Grune T. Sarcopenia – Molecular mechanisms and open questions. Ageing Res. Rev. 2021 65 101200 10.1016/j.arr.2020.101200 33130247
    [Google Scholar]
  3. Yin L. Li N. Jia W. Wang N. Liang M. Yang X. Du G. Skeletal muscle atrophy: From mechanisms to treatments. Pharmacol. Res. 2021 172 105807 10.1016/j.phrs.2021.105807 34389456
    [Google Scholar]
  4. Cohen S. Nathan J.A. Goldberg A.L. Muscle wasting in disease: Molecular mechanisms and promising therapies. Nat. Rev. Drug Discov. 2015 14 1 58 74 10.1038/nrd4467 25549588
    [Google Scholar]
  5. Ding S. Dai Q. Huang H. Xu Y. Zhong C. An overview of muscle atrophy. Adv. Exp. Med. Biol. 2018 1088 3 19 10.1007/978‑981‑13‑1435‑3_1 30390245
    [Google Scholar]
  6. Huang L. Li M. Deng C. Qiu J. Wang K. Chang M. Zhou S. Gu Y. Shen Y. Wang W. Huang Z. Sun H. Potential therapeutic strategies for skeletal muscle atrophy. Antioxidants 2022 12 1 44 10.3390/antiox12010044 36670909
    [Google Scholar]
  7. He N. Ye H. Exercise and muscle atrophy. Adv. Exp. Med. Biol. 2020 1228 255 267 10.1007/978‑981‑15‑1792‑1_17 32342463
    [Google Scholar]
  8. Bagheri R. Robinson I. Moradi S. Purcell J. Schwab E. Silva T. Baker B. Camera D.M. Muscle protein synthesis responses following aerobic-based exercise or high-intensity interval training with or without protein ingestion: A systematic review. Sports Med. 2022 52 11 2713 2732 10.1007/s40279‑022‑01707‑x 35675022
    [Google Scholar]
  9. Drummond M.J. Dreyer H.C. Fry C.S. Glynn E.L. Rasmussen B.B. Nutritional and contractile regulation of human skeletal muscle protein synthesis and mTORC1 signaling. J. Appl. Physiol. 2009 106 4 1374 1384 10.1152/japplphysiol.91397.2008 19150856
    [Google Scholar]
  10. Rehman S.U. Ali R. Zhang H. Zafar M.H. Wang M. Research progress in the role and mechanism of Leucine in regulating animal growth and development. Front. Physiol. 2023 14 1252089 10.3389/fphys.2023.1252089 38046946
    [Google Scholar]
  11. Costamagna D. Costelli P. Sampaolesi M. Penna F. Role of inflammation in muscle homeostasis and myogenesis. Mediators Inflamm. 2015 2015 1 805172 10.1155/2015/805172 26508819
    [Google Scholar]
  12. Ji Y. Li M. Chang M. Liu R. Qiu J. Wang K. Deng C. Shen Y. Zhu J. Wang W. Xu L. Sun H. Inflammation: Roles in skeletal muscle atrophy. Antioxidants 2022 11 9 1686 10.3390/antiox11091686 36139760
    [Google Scholar]
  13. Chen H. Huang X. Dong M. Wen S. Zhou L. Yuan X. The association between sarcopenia and diabetes: From pathophysiology mechanism to therapeutic strategy. Diabetes Metab. Syndr. Obes. 2023 16 1541 1554 10.2147/DMSO.S410834 37275941
    [Google Scholar]
  14. Hirata Y. Nomura K. Senga Y. Okada Y. Kobayashi K. Okamoto S. Minokoshi Y. Imamura M. Takeda S. Hosooka T. Ogawa W. Hyperglycemia induces skeletal muscle atrophy via a WWP1/KLF15 axis. JCI Insight 2019 4 4 e124952 10.1172/jci.insight.124952 30830866
    [Google Scholar]
  15. González P. Lozano P. Ros G. Solano F. Hyperglycemia and oxidative stress: An integral, updated and critical overview of their metabolic interconnections. Int. J. Mol. Sci. 2023 24 11 9352 10.3390/ijms24119352 37298303
    [Google Scholar]
  16. Krause M.P. Riddell M.C. Hawke T.J. Effects of type 1 diabetes mellitus on skeletal muscle: Clinical observations and physiological mechanisms. Pediatr. Diabetes 2011 12 4pt1 345 364 10.1111/j.1399‑5448.2010.00699.x 20860561
    [Google Scholar]
  17. Ratan Z.A. Haidere M.F. Hong Y.H. Park S.H. Lee J.O. Lee J. Cho J.Y. Pharmacological potential of ginseng and its major component ginsenosides. J. Ginseng Res. 2021 45 2 199 210 10.1016/j.jgr.2020.02.004 33841000
    [Google Scholar]
  18. Liu T. Zhu L. Wang L. A narrative review of the pharmacology of ginsenoside compound K. Ann. Transl. Med. 2022 10 4 234 10.21037/atm‑22‑501 35280413
    [Google Scholar]
  19. Jeong H.J. So H.K. Jo A. Kim H.B. Lee S.J. Bae G.U. Kang J.S. Ginsenoside Rg1 augments oxidative metabolism and anabolic response of skeletal muscle in mice. J. Ginseng Res. 2019 43 3 475 481 10.1016/j.jgr.2018.04.005 31308819
    [Google Scholar]
  20. Ghafouri-Fard S. Balaei N. Shoorei H. Hasan S.M.F. Hussen B.M. Talebi S.F. Taheri M. Ayatollahi S.A. The effects of Ginsenosides on PI3K/AKT signaling pathway. Mol. Biol. Rep. 2022 49 7 6701 6716 10.1007/s11033‑022‑07270‑y 35220526
    [Google Scholar]
  21. Lee H.M. Lee O.H. Kim K.J. Lee B.Y. Ginsenoside Rg1 promotes glucose uptake through activated AMPK pathway in insulin-resistant muscle cells. Phytother. Res. 2012 26 7 1017 1022 10.1002/ptr.3686 22170817
    [Google Scholar]
  22. He M. Halima M. Xie Y. Schaaf M.J.M. Meijer A.H. Wang M. Ginsenoside Rg1 Acts as a selective glucocorticoid receptor agonist with anti-inflammatory action without affecting tissue regeneration in zebrafish larvae. Cells 2020 9 5 1107 10.3390/cells9051107 32365641
    [Google Scholar]
  23. Gao Y. Li J. Wang J. Li X. Li J. Chu S. Li L. Chen N. Zhang L. Ginsenoside Rg1 prevent and treat inflammatory diseases: A review. Int. Immunopharmacol. 2020 87 106805 10.1016/j.intimp.2020.106805 32731179
    [Google Scholar]
  24. Aldoss A. Lambarte R. Alsalleeh F. High-glucose media reduced the viability and induced differential pro-inflammatory cytokines in human periodontal ligament fibroblasts. Biomolecules 2023 13 4 690 10.3390/biom13040690 37189437
    [Google Scholar]
  25. Chandrasekaran K. Swaminathan K. Mathan Kumar S. Clemens D.L. Dey A. In vitro evidence for chronic alcohol and high glucose mediated increased oxidative stress and hepatotoxicity. Alcohol. Clin. Exp. Res. 2012 36 6 1004 1012 10.1111/j.1530‑0277.2011.01697.x 22309822
    [Google Scholar]
  26. Chung M.Y. Choi H.K. Hwang J.T. AMPK activity: A primary target for diabetes prevention with therapeutic phytochemicals. Nutrients 2021 13 11 4050 10.3390/nu13114050 34836306
    [Google Scholar]
  27. Zong Y. Yu W. Hong H. Zhu Z. Xiao W. Wang K. Xu G. Ginsenoside Rg1 improves inflammation and autophagy of the pancreas and spleen in streptozotocin-induced type 1 diabetic mice. Int. J. Endocrinol. 2023 2023 1 14 10.1155/2023/3595992 36960388
    [Google Scholar]
  28. Liu Q. Zhang F.G. Zhang W.S. Pan A. Yang Y.L. Liu J.F. Li P. Liu B.L. Qi L.W. Ginsenoside Rg1 inhibits glucagon-induced hepatic gluconeogenesis through Akt-FoxO1 interaction. Theranostics 2017 7 16 4001 4012 10.7150/thno.18788 29109794
    [Google Scholar]
  29. Yoon M.S. mTOR as a key regulator in maintaining skeletal muscle mass. Front. Physiol. 2017 8 788 10.3389/fphys.2017.00788 29089899
    [Google Scholar]
  30. Kim J.H. Yi Y.S. Kim M.Y. Cho J.Y. Role of ginsenosides, the main active components of Panax ginseng, in inflammatory responses and diseases. J. Ginseng Res. 2017 41 4 435 443 10.1016/j.jgr.2016.08.004 29021688
    [Google Scholar]
  31. Li F. Li X. Peng X. Sun L. Jia S. Wang P. Ma S. Zhao H. Yu Q. Huo H. Ginsenoside Rg1 prevents starvation-induced muscle protein degradation via regulation of AKT/mTOR/FoxO signaling in C2C12 myotubes. Exp. Ther. Med. 2017 14 2 1241 1247 10.3892/etm.2017.4615 28781621
    [Google Scholar]
  32. Go G.Y. Lee S.J. Jo A. Lee J. Seo D.W. Kang J.S. Kim S.K. Kim S.N. Kim Y.K. Bae G.U. Ginsenoside Rg1 from Panax ginseng enhances myoblast differentiation and myotube growth. J. Ginseng Res. 2017 41 4 608 614 10.1016/j.jgr.2017.05.006 29021711
    [Google Scholar]
  33. D’Souza D.M. Al-Sajee D. Hawke T.J. Diabetic myopathy: Impact of diabetes mellitus on skeletal muscle progenitor cells. Front. Physiol. 2013 4 379 10.3389/fphys.2013.00379 24391596
    [Google Scholar]
  34. Schiaffino S. Dyar K.A. Ciciliot S. Blaauw B. Sandri M. Mechanisms regulating skeletal muscle growth and atrophy. FEBS J. 2013 280 17 4294 4314 10.1111/febs.12253 23517348
    [Google Scholar]
  35. Bodine S.C. Baehr L.M. Skeletal muscle atrophy and the E3 ubiquitin ligases MuRF1 and MAFbx/atrogin-1. Am. J. Physiol. Endocrinol. Metab. 2014 307 6 E469 E484 10.1152/ajpendo.00204.2014 25096180
    [Google Scholar]
  36. Alway S.E. McCrory J.L. Kearcher K. Vickers A. Frear B. Gilleland D.L. Bonner D.E. Thomas J.M. Donley D.A. Lively M.W. Mohamed J.S. Resveratrol enhances exercise-induced cellular and functional adaptations of skeletal muscle in older men and women. J. Gerontol. A Biol. Sci. Med. Sci. 2017 72 12 1595 1606 10.1093/gerona/glx089 28505227
    [Google Scholar]
  37. Meador B.M. Mirza K.A. Tian M. Skelding M.B. Reaves L.A. Edens N.K. Tisdale M.J. Pereira S.L. The green tea polyphenol Epigallocatechin-3-Gallate (EGCg) attenuates skeletal muscle atrophy in a rat model of sarcopenia. J. Frailty Aging 2015 4 4 1 7 10.14283/jfa.2015.58 27031020
    [Google Scholar]
  38. Weijs P.J.M. Looijaard W.G.P.M. Dekker I.M. Stapel S.N. Girbes A.R. Straaten H.M.O. Beishuizen A. Low skeletal muscle area is a risk factor for mortality in mechanically ventilated critically ill patients. Crit. Care 2014 18 1 R12 10.1186/cc13189 24410863
    [Google Scholar]
/content/journals/cmm/10.2174/0115665240355315250414051525
Loading
Ginsenoside Rg1 Attenuates Muscle Atrophy in Hyperglycemic Conditions, Inactivity and Protein Deprivation Models via AKT/mTOR Pathway Activation
Bentham Science Publishers ; https://doi.org/10.2174/0115665240355315250414051525
/content/journals/cmm/10.2174/0115665240355315250414051525
/content/journals/cmm/10.2174/0115665240355315250414051525
Loading

Data & Media loading...


  • Article Type:     Research Article
Keywords: AKT/mTOR Pathway ; Inactivity ; Ginsenoside Rg1 ; Protein Restriction ; Hyperglycemia ; C2C12 Myoblasts ; Muscle Atrophy

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test