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http://dx.doi.org/10.1016/j.jgr.2021.12.001

Long-term administration of red ginseng non-saponin fraction rescues the loss of skeletal muscle mass and strength associated with aging in mice  

Cho, Da-Eun (Department of Biomedical Sciences, Graduate School, Kyung Hee University)
Choi, Gwang-Muk (Department of Biomedical Sciences, Graduate School, Kyung Hee University)
Lee, Yong-Seok (Department of Biomedical Sciences, Graduate School, Kyung Hee University)
Hong, Joon-Pyo (Department of Biomedical Sciences, Graduate School, Kyung Hee University)
Yeom, Mijung (Acupuncture and Meridian Science Research Center, Kyung Hee University)
Lee, Bombi (Acupuncture and Meridian Science Research Center, Kyung Hee University)
Hahm, Dae-Hyun (Department of Biomedical Sciences, Graduate School, Kyung Hee University)
Publication Information
Journal of Ginseng Research / v.46, no.5, 2022 , pp. 657-665 More about this Journal
Abstract
Background: Sarcopenia is a new and emerging risk factor aggravating the quality of life of elderly population. Because Korean Red Ginseng (RG) is known to have a great effect on relieving fatigue and enhancing physical performance, it is invaluable to examine its potential as an anti-sarcopenic drug. Methods: Anti-sarcopenic effect of non-saponin fraction of Korean Red Ginseng (RGNS) was evaluated in C2C12 myoblasts treated with C2-ceramide to induce senescence phenotypes, and 22-month-old mice fed with chow diet containing 2% RGNS (w/w) for 4 further months. Results: The RGNS treatment significantly alleviated cellular senescence indicated by intracellular lipid accumulation, increased amount of lysosomal β-galactosidase, and reduced proliferative capacity in C2C12 myoblasts. This effect was not observed with saponin fraction. In an aged mouse, the 4-month-RGNS diet significantly improved aging-associated loss of muscle mass and strength, assessed by the weights of hindlimb skeletal muscles such as tibialis anterior (TA), extensor digitorum longus (EDL), gastrocnemius (GN) and soleus (SOL), and the cross-sectional area (CSA) of SOL muscle, and the behaviors in grip strength and hanging wire tests, respectively. During the same period, an aging-associated shift of fast-to slow-twitch muscle in SOL muscle was also retarded by the RGNS treatment. Conclusions: These findings suggested that the long-term diet of RGNS significantly prevented aging-associated muscle atrophy and reduced physical performance, and thus RGNS has a strong potential to be developed as a drug that prevents or improves sarcopenia.
Keywords
Non-saponin fraction of Korean Red Ginseng; Sarcopenia; Muscle atrophy; C2C12 myoblast; Aged mouse;
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1 Miljikovic N, Lim JY, Iva M, Frontera WR. Aging of skeletal muscle fibers. Ann Rehabil Med 2015;39:155-62.   DOI
2 Woo J. Sarcopenia. Clin Geriatr Med 2017;33:305-14.   DOI
3 Enwere EK, Lacasse EC, Adam NJ, Korneluk RG. Role of the TWEAK-Fn14- cIAP1-NF-kB signaling axis in the regulation of myogenesis and muscle homeostasis. Front Immunol 2014;5:34.
4 Kwak JY, Kwon KS. Pharmacological interventions for treatment of sarcopenia: current status of drug development for sarcopenia. Ann Geriatr Med Res 2019;23:98-104.   DOI
5 Kim YH, Park HR, Cha SY, Lee SH, Jo JW, Go JN, Lee KH, Lee SY, Shin SS. Effect of red ginseng natural GEL on skin aging. J Ginseng Res 2020;44:115-22.   DOI
6 Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, Medrano EE, Linskens M, Rubelj I, Pereira-Smith O, Peacocke M, Campisi J. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci USA 1995;92:9363-7.   DOI
7 Augusto V, Padovani CR, Campos GER. Skeletal muscle fiber types in C57BL/6J mice. Braz J Morphol Sci 2004;21:89-94.
8 Rossi MN, Antonangeli F. Cellular response upon stress: p57 contribution to the final outcome. Mediat Inflamm 2015;2015:259325.
9 Zhu S, Tian Z, Torigoe D, Zhao J, Xie P, Sugizaki T, Sato M, Horiguchi H, Terada K, Dadomatsu T, et al. Aging- and obesity-related peri-muscular adipose tissue accelerates muscle atrophy. PLoS One 2019;14:e0221366.   DOI
10 Lopes-Paciencia S, Saint-Germain E, Rowell M-C, Ruiz AF, Kalegari P, Ferbeyre G. The senescence-associated secretory phenotype and its regulation. Cytokine 2019;117:15-22.   DOI
11 Gumucio JP, Mendias CL. Atrogin-1, MuRF-1, and sarcopenia. Endocrine 2013;43:12-21.   DOI
12 Natanek SA, Riddoch-Contreras J, Marsh GS, Hopkinson NS, Moxham J, Man WD, Kemp PR, Polkey MI. MuRF-1 and atrogin-1 protein expression and quadriceps fiber size and muscle mass in stable patients with COPD. COPD 2013;10:618-24.   DOI
13 Rossi MN, Antonangeli F. Cellular response upon stress: p57 contribution to the final outcome. Mediat Inflamm 2015;2015:259325.
14 Claflin DR, Larkin LM, Cederna PS, Horowitz JF, Alexander NB, Cole NM, Galecki AT, Chen S, Nyquist LV, Carlson BM, et al. Effects of high- and lowvelocity resistance training on the contractile properties of skeletal muscle fibers from young and older humans. J Appl Physiol 1985;111(2011): 1021-30.   DOI
15 Jang DJ, Lee MS, Shin BC, Lee YC, Ernst E. Red ginseng for treating erectile dysfunction: a systematic review. Br J Clin Pharmacol 2008;66:444-50.   DOI
16 White ZR. Protein homeostasis and sarcopenia: the influence of fasting and exercise on protein synthesis and degradation pathways [dissertation]. Crawley (WA): University of Western Australia; 2016.
17 Hou J, Yun Y, Xue J, Jeo B, Kim S. Doxorubicin-induced normal breast epithelial cellular aging and its related breast cancer growth through mitochondrial autophagy and oxidative stress mitigated by ginsenoside Rh2. Phytother Res 2020;34:1659-69.   DOI
18 Brook MS, Wilkinson DJ, Phillips BE, Perez-schindler J, Phip A, Smith K, Atherton PJ. Skeletal muscle homeostasis and plasticity in youth and ageing: impact of nutrition and exercise. Acta Physiol 2016;216:15-41.   DOI
19 Wen Y, Bi P, Liu W, Asakura A, Keller C, Kuang S. Constitutive Notch activation upregulates PAX7 and promotes the self-renewal of skeletal muscle satellite cells. Mol Cell Biol 2012;32:2300-11.   DOI
20 Sharples AP, Al-Shanti N, Lewis MP, Stewart CE. Reduction of myoblast differentiation following multiple population doublings in mouse C2C12 cells: a model to investigate ageing. J Cell Biochem 2011;112:3773-85.   DOI
21 Lee SM, Bae BS, Park HW, Ahn NG, Cho BG, Cho YL, Kwak YS. Characterization of Korean red ginseng (Panax ginseng Meyer): history, preparation method, and chemical composition. J Ginseng Res 2015;39:384-91.   DOI
22 Dong Z, Xu M, Huang J, Chen L, Xia J, Chen X, Jiang R, Wang L, Wang Y. The protective effect of ginsenoside Rg1 on aging mouse pancreas damage induced by D-galactose. Exp Ther Med 2017;14:616-22.   DOI
23 Nam GY, Go SR, Choe GJ. Relationship of saponin and non-saponin for the quality of ginseng. J Ginseng Res 1998;22:274-83.
24 Choi KM. Sarcopenia and sarcopenic obesity. Korean J Intern Med 2016;31: 1054-60.   DOI
25 Morley JE, Malmstrom TK, Rodriguez-Manas L, Sinclair AJ. Frailty, sarcopenia and diabetes. J Am Med Dir Assoc 2014;15:853-9.   DOI
26 Lee M, Oilkawa S, Ushida T, Suzuki K, Akimoto T. Effects of exercise training on growth and differentiation factor 11 expression in aged mice. Front Physiol 2019;10:970.
27 Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, Martin FC, Michel JP, Rolland Y, Schneider SM, et al. Sarcopenia: European consensus on definition and diagnosis: report of the European working group on sarcopenia in older people. Age Ageing 2010;39:412-23.   DOI
28 Zeng Y, Hu W, Jing P, Chen X, Wang Z, Wang L, Wang Y. The regulation of ginsenoside Rg1 upon aging of bone marrow stromal cell contribute to delaying senescence of bone marrow mononuclear cells (BMNCs). Life Sci 2018;209:63-8.   DOI
29 Jadhav KS, Dungan CM, Williamson DL. Metformin limits ceramide-induced senescence in C2C12 myoblast. Mech Ageing Dev 2013;34:548-59.
30 Zhu XF, Liu ZC, Xie BF, Feng GK, Zeng YX. Ceramide induces cell cycle arrest and upregulates p27kip in nasopharyngeal carcinoma cells. Cancer Lett 2003;193:149-54.   DOI
31 LeBrasseur NK, Tchkonia T, Kirkland JL. Cellular senescence and the biology of aging, disease, and frailty. Nestle Nutr Inst Workshop Ser 2015;83:11-8.   DOI
32 Venable ME, Lee JY, Smyth MJ, Bielawska A, Obeid LM. Role of Ceramide in cellular senescence. J Biol Chem 1995;270:30701-8.   DOI
33 Deursen JM. The role of senescence cells in ageing. Nature 2014;509:439-46.   DOI
34 Shankland SJ, Eitner F, Hudkins KL, Goodpaster T, D'Agati V, Alpers CE. Differential expression of cyclin-dependent kinase inhibitors in human glomerular disease: role in podocyte proliferation and maturation. Kidney Int 2000;58:674-83.   DOI
35 Park YC, Lim JD, Kim JB, Lee S. Review of red ginseng in terms of mechanisms for pharmacodynamics and toxicity. J Korean Oriental Med 2012;33(3): 200-30.   DOI