Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Longevity, tumor, and physical vitality in rats consuming ginsenoside Rg1

  • Chao-Chieh, Hsieh (Laboratory of Exercise Biochemistry, University of Taipei) ;
  • Chiung-Yun, Chang (Laboratory of Exercise Biochemistry, University of Taipei) ;
  • Tania Xu Yar, Lee (Laboratory of Exercise Biochemistry, University of Taipei) ;
  • Jinfu, Wu (Laboratory of Exercise Biochemistry, University of Taipei) ;
  • Suchada, Saovieng (Laboratory of Exercise Biochemistry, University of Taipei) ;
  • Yu-Wen, Hsieh (Laboratory of Exercise Biochemistry, University of Taipei) ;
  • Maijian, Zhu (Laboratory of Exercise Biochemistry, University of Taipei) ;
  • Chih-Yang, Huang (Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation) ;
  • Chia-Hua, Kuo (Laboratory of Exercise Biochemistry, University of Taipei)
  • Received : 2020.11.30
  • Accepted : 2021.04.18
  • Published : 2023.03.02
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Abstract

Background: Effects of the major ginsenoside Rg1 on mammalian longevity and physical vitality are rarely reported. Purpose: To examine longevity, tumor, and spontaneous locomotor activity in rats consuming Rg1. Methods: A total of 138 Wistar rats were randomized into 2 groups: control (N = 69) and Rg1 (N = 69). Rg1 (0.1 mg/kg per day) were orally supplemented from 6 months of age until natural death. Spontaneous mobility was measured by video-tracking together with body composition (dual energy x-ray absorptiometry) and inflammation markers at 5, 14, 21, and 28 months of age. Results: No significant differences in longevity (control: 706 days; Rg1: 651 days, p = 0.77) and tumor incidence (control: 19%; Rg1: 12%, p = 0.24) were observed between the two groups. Movement distance in the control group declined significantly by ~60% at 21 months of age, together with decreased TNF-α (p = 0.01) and increased IL-10 (p = 0.02). However, the movement distance in the Rg1 group was maintained ~50% above the control groups (p = 0.01) at 21 months of age with greater magnitudes of TNF-α decreases and IL-10 increases. Glucose, insulin, and body composition (bone, muscle and fat percentages) were similar for both groups during the entire observation period. Conclusion: The results of the study suggest a delay age-dependent decline in physical vitality during late life by lifelong Rg1 consumption. This improvement is associated with inflammatory modulation. Significant effects of Rg1 on longevity and tumorigenesis were not observed.

Keywords

Acknowledgement

This study was supported by grants from Ministry of Science & Technology, Taiwan (107-2410-H-845-019) with Nuliv Science and University of Taipei, Taiwan.

References

  1. Bittles AH, Fulder SJ, Grant EC, Nicholls MR. The effect of ginseng on lifespan and stress responses in mice. Gerontology 1979;25(3):125-31. https://doi.org/10.1159/000212330
  2. Miller SC, Delorme D, Shan JJ. Extract of North American ginseng (Panax quinquefolius), administered to leukemic, juvenile mice extends their life span. J Complement Integr Med 2011;8.
  3. Sievenpiper JL, Arnason JT, Leiter LA, Vuksan V. Variable effects of American ginseng: a batch of American ginseng (Panax quinquefolius L.) with a depressed ginsenoside profile does not affect postprandial glycemia. Eur J Clin Nutr 2003;57(2):243-8. https://doi.org/10.1038/sj.ejcn.1601550
  4. Sievenpiper JL, Arnason JT, Leiter LA, Vuksan V. Decreasing, null and increasing effects of eight popular types of ginseng on acute postprandial glycemic indices in healthy humans: the role of ginsenosides. J Am Coll Nutr 2004;23(3):248-58. https://doi.org/10.1080/07315724.2004.10719368
  5. Chaunchaiyakul R, Leelayuwat N, Wu JF, Huang CY, Kuo CH. Contrasting actions of ginsenosides Rb1 and Rg1 on glucose tolerance in rats. Chin J Physiol 2019;62(6):267-72. https://doi.org/10.4103/cjp.cjp_61_19
  6. Sengupta S, Toh SA, Sellers LA, Skepper JN, Koolwijk P, Leung HW, Yeung HW, Wong RN, Sasisekharan R, Fan TP. Modulating angiogenesis: the yin and the yang in ginseng. Circulation 2004;110(10):1219-25. https://doi.org/10.1161/01.CIR.0000140676.88412.CF
  7. Zhang Y, Hu W, Zhang B, Yin Y, Zhang J, Huang D, Huang R, Li W, Li W. Ginsenoside Rg1 protects against neuronal degeneration induced by chronic dexamethasone treatment by inhibiting NLRP-1 inflammasomes in mice. Int J Mol Med 2017;40(4):1134-42. https://doi.org/10.3892/ijmm.2017.3092
  8. Wu J, Saovieng S, Cheng IS, Liu T, Hong S, Lin CY, Su IC, Huang CY, Kuo CH. Ginsenoside Rg1 supplementation clears senescence-associated b-galactosidase in exercising human skeletal muscle. J Ginseng Res 2019;43(4):580-8. https://doi.org/10.1016/j.jgr.2018.06.002
  9. Jiang W, Wang Z, Jiang Y, Lu M, Li X. Ginsenoside Rg1 ameliorates motor function in an animal model of Parkinson's disease. Pharmacology 2015;96(1-2):25-31. https://doi.org/10.1159/000431100
  10. Jiang B, Xiong Z, Yang J, Wang W, Wang Y, Hu Z-L, Wang F, Chen J-G. Antidepressant-like effects of ginsenoside Rg1 are due to activation of the BDNF signalling pathway and neurogenesis in the hippocampus. Br J Pharmacol 2012;166(6):1872-87. https://doi.org/10.1111/j.1476-5381.2012.01902.x
  11. Byberg L, Melhus H, Gedeborg R, Sundstrom J, Ahlbom A, Zethelius B, Berglund LG, Wolk A, Michaelsson K. Total mortality after changes in leisure € time physical activity in 50 year old men: 35 year follow-up of population based cohort. BMJ 2009;338:b688.
  12. Lee SY, Jeong JJ, Eun SH, Kim DH. Anti-inflammatory effects of ginsenoside Rg1 and its metabolites ginsenoside Rh1 and 20(S)-protopanaxatriol in mice with TNBS-induced colitis. Eur J Pharmacol 2015;762:333-43. https://doi.org/10.1016/j.ejphar.2015.06.011
  13. Candore G, Caruso C, Jirillo E, Magrone T, Vasto S. Low grade inflammation as a common pathogenetic denominator in age-related diseases: novel drug targets for anti-ageing strategies and successful ageing achievement. Curr Pharm Des 2010;16(6):584-96. https://doi.org/10.2174/138161210790883868
  14. Almanan M, Raynor J, Ogunsulire I, Malyshkina A, Mukherjee S, Hummel SA, Ingram JT, Saini A, Xie MM, Alenghat T, et al. IL-10-producing Tfh cells accumulate with age and link inflammation with age-related immune suppression. Sci Adv 2020;6(31):eabb0806.
  15. Wang Y, Wehling-Henricks M, Samengo G, Tidball JG. Increases of M2a macrophages and fibrosis in aging muscle are influenced by bone marrow aging and negatively regulated by muscle-derived nitric oxide. Aging Cell 2015;14(4):678-88. https://doi.org/10.1111/acel.12350
  16. Tidball JG. Regulation of muscle growth and regeneration by the immune system. Nat Rev Immunol 2017;17(3):165-78. https://doi.org/10.1038/nri.2016.150
  17. Wu J, Saovieng S, Cheng IS, Jensen J, Jean W-H, Alkhatib A, Kao C-L, Huang C-Y, Kuo C-H. Satellite cells depletion in exercising human skeletal muscle is restored by ginseng component Rg1 supplementation. J Func Foods 2019;58: 27-33. https://doi.org/10.1016/j.jff.2019.04.032
  18. Malley LA, Kennedy GL, Elliott GS, Slone TW, Mellert W, Deckardt K, Kuttler K, Hildebrand B, Banton MI, Parod RJ, et al. Chronic toxicity and oncogenicity of N-methylpyrrolidone (NMP) in rats and mice by dietary administration. Drug Chem Toxicol 2001;24(4):315-38. https://doi.org/10.1081/DCT-100106262
  19. Liu H, Wang J, Liu M, Zhao H, Yaqoob S, Zheng M, Cai D, Liu J. Antiobesity effects of ginsenoside Rg1 on 3T3-L1 preadipocytes and high fat diet-induced obese mice mediated by AMPK. Nutrients 2018;10(7).
  20. Schafer MJ, White TA, Evans G, Tonne JM, Verzosa GC, Stout MB, Mazula DL, Palmer AK, Baker DJ, Jensen MD, et al. Exercise prevents diet-induced cellular senescence in adipose tissue. Diabetes 2016;65(6):1606-15. https://doi.org/10.2337/db15-0291
  21. W€ arnberg J, Moreno LA, Mesana MI, Marcos A. Inflammatory mediators in overweight and obese Spanish adolescents. The AVENA Study. Int J Obes Relat Metab Disord 2004;28(Suppl 3):S59-63. https://doi.org/10.1038/sj.ijo.0802809
  22. Ratcliff WC, Denison RF, Borrello M, Travisano M. Experimental evolution of multicellularity. Proc Natl Acad Sci U S A 2012;109(5):1595-600. https://doi.org/10.1073/pnas.1115323109
  23. Lasry A, Ben-Neriah Y. Senescence-associated inflammatory responses: aging and cancer perspectives. Trends Immunol 2015;36(4):217-28. https://doi.org/10.1016/j.it.2015.02.009
  24. Sorensen JR, Kaluhiokalani JP, Hafen PS, Deyhle MR, Parcell AC, Hyldahl RD. An altered response in macrophage phenotype following damage in aged human skeletal muscle: implications for skeletal muscle repair. FASEB J 2019;33(9): 10353-68. https://doi.org/10.1096/fj.201900519r
  25. Jung M, Ma Y, Iyer RP, DeLeon-Pennell KY, Yabluchanskiy A, Garrett MR, Lindsey ML. IL-10 improves cardiac remodeling after myocardial infarction by stimulating M2 macrophage polarization and fibroblast activation. Basic Res Cardiol 2017;112(3):33.
  26. Wang F, Dai Y, Xu T, Xu B, Wang K. Effect of IL-10 on formation of foam cell induced by ox-LDL. Frontiers Med in China 2008;2(3):298e302.
  27. Kessler B, Rinchai D, Kewcharoenwong C, Nithichanon A, Biggart R, Hawrylowicz CM, Bancroft GJ, Lertmemongkolchai G. Interleukin 10 inhibits pro-inflammatory cytokine responses and killing of Burkholderia pseudomallei. Sci Rep 2017;7(1):42791.
  28. Meador BM, Krzyszton CP, Johnson RW, Huey KA. Effects of IL-10 and age on IL-6, IL-1b, and TNF-a responses in mouse skeletal and cardiac muscle to an acute inflammatory insult. J Appl Physiol 2008;104(4):991-7. https://doi.org/10.1152/japplphysiol.01079.2007
  29. Luo J, Hendryx M, Manson JE, Figueiredo JC, LeBlanc ES, Barrington W, Rohan TE, Howard BV, Reding K, Ho GY, et al. Intentional weight loss and obesity-related cancer risk. JNCI Cancer Spectr 2019;3(4):pkz054.
  30. Hsu MF, Yu SH, Korivi M, Jean WH, Lee SD, Huang CY, Liao YH, Lu J, Kuo CH. Hormetic property of ginseng steroids on anti-oxidant status against exercise challenge in rat skeletal muscle. Antioxidants (Basel) 2017;6(2).
  31. Won HJ, Kim HI, Park T, Kim H, Jo K, Jeon H, Ha SJ, Hyun JM, Jeong A, Kim JS, et al. Non-clinical pharmacokinetic behavior of ginsenosides. J Ginseng Res 2019;43(3):354-60. https://doi.org/10.1016/j.jgr.2018.06.001