Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Gintonin-enriched fraction improves sarcopenia by maintaining immune homeostasis in 20- to 24-month-old C57BL/6J mice

  • Oh, Hyun-Ji (Department of Food Science and Biotechnology, College of Life Science, CHA University) ;
  • Jin, Heegu (Department of Food Science and Biotechnology, College of Life Science, CHA University) ;
  • Nah, Seung-Yeol (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University) ;
  • Lee, Boo-Yong (Department of Food Science and Biotechnology, College of Life Science, CHA University)
  • Received : 2021.05.14
  • Accepted : 2021.07.19
  • Published : 2021.11.15
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Abstract

Background: Gintonin-enriched fraction (GEF) is a new non-saponin component glycolipoprotein isolated from ginseng root. This study examined the effect of GEF on age-related sarcopenia in old C57BL/6J mice. Methods: Young (3-6 months) and old (20-24 months) C57BL/6J mice received oral GEF (50 mg/kg/day or 150 mg/kg/day) daily for 5 weeks. During the oral administration period, body weight and grip strength were measured weekly. After sacrifice, muscles from the hindlimb were excised and used for hematoxylin and eosin staining and western blotting to determine the effects of GEF on sarcopenia. The thymus was photographed to compare size, and flow cytometry was performed to examine the effect of GEF on immune homeostasis in the thymus and spleen. Blood samples were collected, and the concentrations of pro-inflammatory cytokines and IGF-1 were measured. Results: GEF caused a significant increase in muscle strength, mass, and fiber size in old mice. GEF restored age-related disruption of immune homeostasis by maintaining T cell compartments and regulating inflammatory biomarkers. Thus, GEF reduced common low-grade chronic inflammatory parameters, which are the main cause of muscle loss. Conclusion: GEF maintained immune homeostasis and inhibited markers of chronic inflammation, resulting in anti-sarcopenia effects in aged C57BL/6J mice. Thus, GEF is a potential therapeutic agent that slows sarcopenia in the elderly.

Keywords

Acknowledgement

This work was partially supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2021R1A2C2006180), and by a grant from the Korean Society of Ginseng, funded by the Korean Ginseng Corporation.

References

  1. Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, et al. Sarcopenia: European consensus on definition and diagnosis: report of the European working group on sarcopenia in older people. Age Ageing 2010;39(4):412-23. https://doi.org/10.1093/ageing/afq034
  2. Visser M, Schaap LA. Consequences of sarcopenia. Clin Geriatr Med 2011;27(3):387-99. https://doi.org/10.1016/j.cger.2011.03.006
  3. Visser M. Obesity, sarcopenia and their functional consequences in old age. Proc Nutr Soc 2011;70(1):114-8. https://doi.org/10.1017/S0029665110003939
  4. Ziaaldini MM, Marzetti E, Picca A, Murlasits Z. Biochemical pathways of sarcopenia and their modulation by physical exercise: a narrative review. Front Med (Lausanne). 2017;4:167. https://doi.org/10.3389/fmed.2017.00167
  5. Bonaldo P, Sandri M. Cellular and molecular mechanisms of muscle atrophy. Dis Model Mech 2013;6(1):25-39. https://doi.org/10.1242/dmm.010389
  6. Frontera WR, Ochala J. Skeletal muscle: a brief review of structure and function. Calcif Tissue Int 2015;96(3):183-95. https://doi.org/10.1007/s00223-014-9915-y
  7. Robinson S, Cooper C, Aihie Sayer A. Nutrition and sarcopenia: a review of the evidence and implications for preventive strategies. J Aging Res 2012;2012:510801. https://doi.org/10.1155/2012/510801
  8. Kwon YN, Yoon SS. Sarcopenia: neurological point of view. J Bone Metab 2017;24(2):83-9. https://doi.org/10.11005/jbm.2017.24.2.83
  9. Thomas R, Wang W, Su DM. Contributions of age-related thymic involution to immunosenescence and inflammaging. Immun Ageing 2020;17:2. https://doi.org/10.1186/s12979-020-0173-8
  10. Tu W, Rao S. Mechanisms underlying T cell immunosenescence: aging and cytomegalovirus infection. Front Microbiol 2016;7:2111.
  11. Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca M, Ottaviani E, et al. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci 2000;908:244-54.
  12. Chei S, Oh HJ, Lee K, Jin H, Lee JY, Lee BY. Dysfunction of B Cell leading to failure of immunoglobulin response is ameliorated by dietary silk peptide in 14-month-old C57BL/6 mice. Front Nutr 2020;7:583186. https://doi.org/10.3389/fnut.2020.583186
  13. Palmer DB. The effect of age on thymic function. Front Immunol 2013;4:316. https://doi.org/10.3389/fimmu.2013.00316
  14. Shen SS, Kim JS, Weksler ME. Effect of age on thymic development, T cell immunity, and helper T cell function. Rev Physiol Biochem Pharmacol 1999;139:123-39. https://doi.org/10.1007/BFb0033650
  15. Dalle S, Rossmeislova L, Koppo K. The role of inflammation in age-related sarcopenia. Front Physiol 2017;8:1045. https://doi.org/10.3389/fphys.2017.01045
  16. Curcio F, Ferro G, Basile C, Liguori I, Parrella P, Pirozzi F, et al. Biomarkers in sarcopenia: a multifactorial approach. Exp Gerontol 2016;85:1-8. https://doi.org/10.1016/j.exger.2016.09.007
  17. Meng SJ, Yu LJ. Oxidative stress, molecular inflammation and sarcopenia. Int J Mol Sci 2010;11(4):1509-26. https://doi.org/10.3390/ijms11041509
  18. Nelke C, Dziewas R, Minnerup J, Meuth SG, Ruck T. Skeletal muscle as potential central link between sarcopenia and immune senescence. EBioMedicine 2019;49:381-8. https://doi.org/10.1016/j.ebiom.2019.10.034
  19. Bano G, Trevisan C, Carraro S, Solmi M, Luchini C, Stubbs B, et al. Inflammation and sarcopenia: a systematic review and meta-analysis. Maturitas 2017;96:10-5. https://doi.org/10.1016/j.maturitas.2016.11.006
  20. Chhetri JK, de Souto Barreto P, Fougere B, Rolland Y, Vellas B, Cesari M. Chronic inflammation and sarcopenia: a regenerative cell therapy perspective. Exp Gerontol 2018;103:115-23. https://doi.org/10.1016/j.exger.2017.12.023
  21. Cho HJ, Choi SH, Kim HJ, Lee BH, Rhim H, Kim HC, et al. Bioactive lipids in gintonin-enriched fraction from ginseng. J Ginseng Res 2019;43(2):209-17. https://doi.org/10.1016/j.jgr.2017.11.006
  22. Chei S, Song JH, Oh HJ, Lee K, Jin H, Choi SH, et al. Gintonin-enriched fraction suppresses heat stress-induced inflammation through LPA receptor. Molecules 2020;25(5).
  23. Chei S, Oh HJ, Jang H, Lee K, Jin H, Choi Y, et al. Korean red ginseng suppresses the expression of oxidative stress response and NLRP3 inflammasome genes in aged C57BL/6 mouse ovaries. Foods 2020;9(4).
  24. Lee SM, Bae BS, Park HW, Ahn NG, Cho BG, Cho YL, et al. Characterization of Korean red ginseng (panax ginseng meyer): history, preparation method, and chemical composition. J Ginseng Res 2015;39(4):384-91. https://doi.org/10.1016/j.jgr.2015.04.009
  25. Hwang SH, Shin EJ, Shin TJ, Lee BH, Choi SH, Kang J, et al. Gintonin, a ginseng-derived lysophosphatidic acid receptor ligand, attenuates Alzheimer's disease-related neuropathies: involvement of non-amyloidogenic processing. J Alzheimers Dis 2012;31(1):207-23. https://doi.org/10.3233/JAD-2012-120439
  26. Pyo MK, Choi SH, Shin TJ, Hwang SH, Lee BH, Kang J, et al. A simple method for the preparation of crude gintonin from ginseng root, stem, and leaf. J Ginseng Res 2011;35(2):209-18. https://doi.org/10.5142/jgr.2011.35.2.209
  27. Choi SH, Jung SW, Kim HS, Kim HJ, Lee BH, Kim JY, et al. A brief method for preparation of gintonin-enriched fraction from ginseng. J Ginseng Res 2015;39(4):398-405. https://doi.org/10.1016/j.jgr.2015.05.002
  28. Choi SH, Hong MK, Kim HJ, Ryoo N, Rhim H, Nah SY, et al. Structure of ginseng major latex-like protein 151 and its proposed lysophosphatidic acid-binding mechanism. Acta Crystallogr D Biol Crystallogr 2015;71(Pt 5):1039-50. https://doi.org/10.1107/S139900471500259X
  29. Lee BH, Kim HK, Jang M, Kim HJ, Choi SH, Hwang SH, et al. Effects of gintonin-enriched fraction in an atopic dermatitis animal model: involvement of autotaxin regulation. Biol Pharm Bull 2017;40(7):1063-70. https://doi.org/10.1248/bpb.b17-00124
  30. Choi JH, Jang M, Oh S, Nah SY, Cho IH. Multi-target protective effects of gintonin in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Mediated model of Parkinson's disease via lysophosphatidic acid receptors. Front Pharmacol 2018;9:515. https://doi.org/10.3389/fphar.2018.00515
  31. Nair AB, Jacob S. A simple practice guide for dose conversion between animals and human. J Basic Clin Pharm 2016;7(2):27-31. https://doi.org/10.4103/0976-0105.177703
  32. Farini A, Sitzia C, Villa C, Cassani B, Tripodi L, Legato M, et al. Defective dystrophic thymus determines degenerative changes in skeletal muscle. Nat Commun 2021;12(1):2099. https://doi.org/10.1038/s41467-021-22305-x
  33. Bektas A, Schurman SH, Sen R, Ferrucci L. Human T cell immunosenescence and inflammation in aging. J Leukoc Biol 2017;102(4):977-88. https://doi.org/10.1189/jlb.3RI0716-335R
  34. Wang HX, Pan W, Zheng L, Zhong XP, Tan L, Liang Z, et al. Thymic epithelial cells contribute to thymopoiesis and T cell development. Front Immunol 2019;10:3099. https://doi.org/10.3389/fimmu.2019.03099
  35. Dutta S, Sengupta P. Men and mice: relating their ages. Life Sci 2016;152:244-8. https://doi.org/10.1016/j.lfs.2015.10.025
  36. Anthony TG. Mechanisms of protein balance in skeletal muscle. Domest Anim Endocrinol 2016;56(Suppl):S23-32. https://doi.org/10.1016/j.domaniend.2016.02.012
  37. Tipton KD, Hamilton DL, Gallagher IJ. Assessing the role of muscle protein breakdown in response to nutrition and exercise in humans. Sports Med 2018;48(Suppl 1):53-64. https://doi.org/10.1007/s40279-017-0845-5
  38. Kim C, Hwang JK. The 5,7-dimethoxyflavone suppresses sarcopenia by regulating protein turnover and mitochondria biogenesis-related pathways. Nutrients 2020;12(4).
  39. Mauricio SF, de Vasconcelos Generoso S, Leandro Marciano Vieira E, Xiao J, Prado CM, Gonzalez MC, et al. Relationship between sarcopenia and mTOR pathway in patients with colorectal cancer: preliminary report. Nutr Cancer 2019;71(1):172-7. https://doi.org/10.1080/01635581.2018.1540716
  40. Yoon MS. mTOR as a key regulator in maintaining skeletal muscle mass. Front Physiol 2017;8:788. https://doi.org/10.3389/fphys.2017.00788
  41. Andre LM, Ausems CRM, Wansink DG, Wieringa B. Abnormalities in skeletal muscle myogenesis, growth, and regeneration in myotonic dystrophy. Front Neurol 2018;9:368. https://doi.org/10.3389/fneur.2018.00368
  42. Charge SB, Rudnicki MA. Cellular and molecular regulation of muscle regeneration. Physiol Rev 2004;84(1):209-38. https://doi.org/10.1152/physrev.00019.2003
  43. Lu J, McKinsey TA, Zhang CL, Olson EN. Regulation of skeletal myogenesis by association of the MEF2 transcription factor with class II histone deacetylases. Mol Cell 2000;6(2):233-44. https://doi.org/10.1016/S1097-2765(00)00025-3
  44. Abrigo J, Rivera JC, Aravena J, Cabrera D, Simon F, Ezquer F, et al. High fat diet-induced skeletal muscle wasting is decreased by mesenchymal stem cells administration: implications on oxidative stress, ubiquitin proteasome pathway activation, and myonuclear apoptosis. Oxid Med Cell Longev 2016;2016:9047821. https://doi.org/10.1155/2016/9047821
  45. Lee C, Jeong H, Lee H, Hong M, Park SY, Bae H. Magnolol attenuates cisplatin-induced muscle wasting by M2c macrophage activation. Front Immunol 2020;11:77. https://doi.org/10.3389/fimmu.2020.00077
  46. Adams GR. Insulin-like growth factor in muscle growth and its potential abuse by athletes. Br J Sports Med 2000;34(6):412-3. https://doi.org/10.1136/bjsm.34.6.412
  47. Beyer I, Mets T, Bautmans I. Chronic low-grade inflammation and age-related sarcopenia. Curr Opin Clin Nutr Metab Care 2012;15(1):12-22. https://doi.org/10.1097/MCO.0b013e32834dd297
  48. Haynes L, Maue AC. Effects of aging on T cell function. Curr Opin Immunol 2009;21(4):414-7. https://doi.org/10.1016/j.coi.2009.05.009
  49. Bredenkamp N, Nowell CS, Blackburn CC. Regeneration of the aged thymus by a single transcription factor. Development 2014;141(8):1627-37. https://doi.org/10.1242/dev.103614
  50. Castilho JL, Shepherd BE, Koethe J, Turner M, Bebawy S, Logan J, et al. CD4+/CD8+ ratio, age, and risk of serious noncommunicable diseases in HIV-infected adults on antiretroviral therapy. AIDS 2016;30(6):899-908. https://doi.org/10.1097/QAD.0000000000001005
  51. Macaulay R, Akbar AN, Henson SM. The role of the T cell in age-related inflammation. Age (Dordr) 2013;35(3):563-72. https://doi.org/10.1007/s11357-012-9381-2
  52. Moro-Garcia MA, Mayo JC, Sainz RM, Alonso-Arias R. Influence of inflammation in the process of T lymphocyte differentiation: proliferative, metabolic, and oxidative changes. Front Immunol 2018;9:339. https://doi.org/10.3389/fimmu.2018.00339
  53. Coder BD, Wang H, Ruan L, Su DM. Thymic involution perturbs negative selection leading to autoreactive T cells that induce chronic inflammation. J Immunol 2015;194(12):5825-37. https://doi.org/10.4049/jimmunol.1500082
  54. Bruunsgaard H, Pedersen M, Pedersen BK. Aging and proinflammatory cytokines. Curr Opin Hematol 2001;8(3):131-6. https://doi.org/10.1097/00062752-200105000-00001
  55. Rong YD, Bian AL, Hu HY, Ma Y, Zhou XZ. Study on relationship between elderly sarcopenia and inflammatory cytokine IL-6, anti-inflammatory cytokine IL-10. BMC Geriatr 2018;18(1):308. https://doi.org/10.1186/s12877-018-1007-9
  56. Wang J, Leung KS, Chow SK, Cheung WH. Inflammation and age-associated skeletal muscle deterioration (sarcopaenia). J Orthop Translat 2017;10:94-101. https://doi.org/10.1016/j.jot.2017.05.006
  57. Bruunsgaard H, Skinhoj P, Pedersen AN, Schroll M, Pedersen BK. Ageing, tumour necrosis factor-alpha (TNF-alpha) and atherosclerosis. Clin Exp Immunol 2000;121(2):255-60. https://doi.org/10.1046/j.1365-2249.2000.01281.x
  58. Ferrucci L, Corsi A, Lauretani F, Bandinelli S, Bartali B, Taub DD, et al. The origins of age-related proinflammatory state. Blood 2005;105(6):2294-9. https://doi.org/10.1182/blood-2004-07-2599
  59. Bruunsgaard H, Andersen-Ranberg K, Jeune B, Pedersen AN, Skinhoj P, Pedersen BK. A high plasma concentration of TNF-alpha is associated with dementia in centenarians. J Gerontol A Biol Sci Med Sci 1999;54(7):M357-64. https://doi.org/10.1093/gerona/54.7.M357