DOI QR코드

DOI QR Code

A network pharmacology approach to explore the potential role of Panax ginseng on exercise performance

  • Kim, Jisu (Physical Activity & Performance Institute, Konkuk University) ;
  • Lee, Kang Pa (Research & Development Center, UMUST R&D Corporation) ;
  • Kim, Myoung-Ryu (Department of Nursing, Cheju Halla University) ;
  • Kim, Bom Sahn (Department of Nuclear Medicine, Ewha Womans University Seoul Hospital, Ewha Womans University College of Medicine) ;
  • Moon, Byung Seok (Department of Nuclear Medicine, Ewha Womans University Seoul Hospital, Ewha Womans University College of Medicine) ;
  • Shin, Chul Ho (Department of Sports Healthcare Management, Namseoul University) ;
  • Baek, Suji (Research & Development Center, UMUST R&D Corporation) ;
  • Hong, Bok Sil (Department of Nursing, Cheju Halla University)
  • Received : 2021.09.13
  • Accepted : 2021.09.29
  • Published : 2021.09.30

Abstract

[Purpose] As Panax ginseng C. A. Meyer (ginseng) exhibits various physiological activities and is associated with exercise, we investigated the potential active components of ginseng and related target genes through network pharmacological analysis. Additionally, we analyzed the association between ginseng-related genes, such as the G-protein-coupled receptors (GPCRs), and improved exercise capacity. [Methods] Active compounds in ginseng and the related target genes were searched in the Traditional Chinese Medicine Database and Analysis Platform (TCMSP). Gene ontology functional analysis was performed to identify biological processes related to the collected genes, and a compound-target network was visualized using Cytoscape 3.7.2. [Results] A total of 21 ginseng active compounds were detected, and 110 targets regulated by 17 active substances were identified. We found that the active compound protein was involved in the biological process of adrenergic receptor activity in 80%, G-protein-coupled neurotransmitter in 10%, and leucocyte adhesion to arteries in 10%. Additionally, the biological response centered on adrenergic receptor activity showed a close relationship with G protein through the beta-1 adrenergic receptor gene reactivity. [Conclusion] According to bioavailability analysis, ginseng comprises 21 active compounds. Furthermore, we investigated the ginseng-stimulated gene activation using ontology analysis. GPCR, a gene upregulated by ginseng, is positively correlated to exercise. Therefore, if a study on this factor is conducted, it will provide useful basic data for improving exercise performance and health.

Keywords

Acknowledgement

This work was supported by the Ministry of Education of the Republic of Korea and the National Research Foundation of Korea (NRF-2019S1A5A8033825). This study was supported by the KU Research Professor Program of Konkuk University.

References

  1. Nobile M. The who definition of health: a critical reading. Med Law. 2014;33:33-40.
  2. Farhud DD. Impact of lifestyle on health. Iran J Public Health. 2015;44:1442-4.
  3. Booth FW, Roberts CK, Laye MJ. Lack of exercise is a major cause of chronic diseases. Compr Physiol. 2012;2:1143-211. https://doi.org/10.1002/cphy.c110025
  4. Koehler K, Drenowatz C. Integrated role of nutrition and physical activity for lifelong health. Nutrients. 2019;11:1437. https://doi.org/10.3390/nu11071437
  5. Balan E, Decottignies A, Deldicque L. Physical activity and nutrition: two promising strategies for telomere maintenance? Nutrients. 2018;10:1942. https://doi.org/10.3390/nu10121942
  6. Ferrer MD, Capo X, Martorell M, Busquets-Cortes C, Bouzas C, Carreres S, Mateos D, Sureda A, Tur JA, Pons A. Regular practice of moderate physical activity by older adults ameliorates their anti-inflammatory status. Nutrients. 2018;10:1780. https://doi.org/10.3390/nu10111780
  7. Husted AS, Trauelsen M, Rudenko O, Hjorth SA, Schwartz TW. GPCR-mediated signaling of metabolites. Cell Metab. 2017;25:777-96. https://doi.org/10.1016/j.cmet.2017.03.008
  8. Huang CJ, Slusher AL, Whitehurst M, Wells M, Mock JT, Maharaj A, Shibata Y. Acute aerobic exercise mediates G protein-coupled receptor kinase 2 expression in human PBMCs. Life Sci. 2015;135:87-91. https://doi.org/10.1016/j.lfs.2015.05.018
  9. Meadows A, Lee JH, Wu CS, Wei Q, Pradhan G, Yafi M, Lu HC, Sun Y. Deletion of G-protein-coupled receptor 55 promotes obesity by reducing physical activity. Int J Obes (Lond). 2016;40:417-24. https://doi.org/10.1038/ijo.2015.209
  10. Yahara S, Kaji K, Tanaka O. Further study on dammarane type of root, leaves, flower-buds, and fruits of Panax ginseng C. A. Meyer. Chem Pharm Bull. 1979;27:88-92. https://doi.org/10.1248/cpb.27.88
  11. Zhao B, Lv C, Lu J. Natural occurring polysaccharides from Panax ginseng C. A. Meyer: a review of isolation, structures, and bioactivities. Int J Biol Macromol. 2019;133:324-36. https://doi.org/10.1016/j.ijbiomac.2019.03.229
  12. Hwang H, Kim J, Lim K. The effect of a 2-week red ginseng supplementation on food efficiency and energy metabolism in mice. Nutrients. 2020;12:1726. https://doi.org/10.3390/nu12061726
  13. Biondo PD, Robbins SJ, Walsh JD, McCargar LJ, Harber VJ, Field CJ. A randomized controlled crossover trial of the effect of ginseng consumption on the immune response to moderate exercise in healthy sedentary men. Appl Physiol Nutr Metab. 2008;33:966-75. https://doi.org/10.1139/H08-080
  14. Hyun SH, Kim SW, Seo HW, Youn SH, Kyung JS, Lee YY, In G, Park CK, Han CK. Physiological and pharmacological features of the non-saponin components in Korean Red Ginseng. J Ginseng Res. 2020;44:527-37. https://doi.org/10.1016/j.jgr.2020.01.005
  15. Suo T, Liu J, Chen X, Yu H, Wang T, Li C, Wang Y, Wang C, Li Z. Combining chemical profiling and network analysis to investigate the pharmacology of complex prescriptions in traditional Chinese medicine. Sci Rep. 2017;7:40529. https://doi.org/10.1038/srep40529
  16. Lv X, Xu Z, Xu G, Li H, Wang C, Chen J, Sun J. Investigation of the active components and mechanisms of Schisandra chinensis in the treatment of asthma based on a network pharmacology approach and experimental validation. Food Funct. 2020;11:3032-42. https://doi.org/10.1039/D0FO00087F
  17. Kelley EF, Snyder EM, Johnson BD. Influence of Beta-1 adrenergic receptor genotype on cardiovascular response to exercise in healthy subjects. Cardiol Res. 2018;9:343-9. https://doi.org/10.14740/cr785
  18. Ru J, Li P, Wang J, Zhou W, Li B, Huang C, Li P, Guo Z, Tao W, Yang Y, Xu X, Li Y, Wang Y, Yang L. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines. J Cheminform. 2014;6:13. https://doi.org/10.1186/1758-2946-6-13
  19. Yang Y, Li Y, Wang J, Sun K, Tao W, Wang Z, Xiao W, Pan Y, Zhang S, Wang Y. Systematic investigation of ginkgo biloba leaves for treating cardio-cerebrovascular diseases in an animal model. ACS Chem Biol. 2017;12:1363-72. https://doi.org/10.1021/acschembio.6b00762
  20. Kiefer D, Pantuso T. Panax ginseng. Am Fam Physician. 2003;68:1539-42.
  21. Shergis JL, Zhang AL, Zhou W, Xue CC. Panax ginseng in randomised controlled trials: a systematic review. Phytother Res. 2013;27:949-65. https://doi.org/10.1002/ptr.4832
  22. Guest NS, VanDusseldorp TA, Nelson MT, Grgic J, Schoenfeld BJ, Jenkins NDM, Arent SM, Antonio J, Stout JR, Trexler ET, Smith-Ryan AE, Goldstein ER, Kalman DS, Campbell BI. International society of sports nutrition position stand: caffeine and exercise performance. J Int Soc Sports Nutr. 2021;18:1. https://doi.org/10.1186/s12970-020-00383-4
  23. Spriet LL. Exercise and sport performance with low doses of caffeine. Sports Med. 2014;44:S175-84.
  24. Hwang D, Seo JB, Kim J, Lim K. Effect of mild-intensity exercise training with capsiate intake on fat deposition and substrate utilization during exercise in diet-induced obese mice. Phys Act Nutr. 2020;24:1-6. https://doi.org/10.20463/pan.2020.0014
  25. Hwang D, Seo JB, Park HY, Kim J, Lim K. Capsiate intake with exercise training additively reduces fat deposition in mice on a high-fat diet, but not without exercise training. Int J Mol Sci. 2021;22:769. https://doi.org/10.3390/ijms22020769
  26. Ahmadian M, Roshan VD, Aslani E, Stannard SR. Taurine supplementation has anti-atherogenic and anti-inflammatory effects before and after incremental exercise in heart failure. Ther Adv Cardiovasc Dis. 2017;11:185-94. https://doi.org/10.1177/1753944717711138
  27. Aminifard T, Razavi BM, Hosseinzadeh H. The effects of ginseng on the metabolic syndrome: an updated review. Food Sci Nutr. 2021;9:5293-311. https://doi.org/10.1002/fsn3.2475
  28. Li Z, Ji GE. Ginseng and obesity. J Ginseng Res. 2018;42:1-8. https://doi.org/10.1016/j.jgr.2016.12.005
  29. Kim HG, Cho JH, Yoo SR, Lee JS, Han JM, Lee NH, Ahn YC, Son CG. Antifatigue effects of Panax ginseng C. A. Meyer: a randomised, double-blind, placebo-controlled trial. PLoS One. 2013;8:e61271. https://doi.org/10.1371/journal.pone.0061271
  30. Kim J, Park J, Lim K. Nutrition supplements to stimulate lipolysis: a review in relation to endurance exercise capacity. J Nutr Sci Vitaminol. 2016;62:141-61. https://doi.org/10.3177/jnsv.62.141
  31. Chang Y, Yu LC, Sung HW. A natural compound (ginsenoside Re) isolated from Panax ginseng as a novel angiogenic agent for tissue regeneration. Pharm Res. 2005;22:636-46. https://doi.org/10.1007/s11095-005-2500-3
  32. Barari A, Daloii AA, Dorooky E. Effects of endurance training and six weeks of ginseng supplementation on serum vascular endothelial growth factor and platelet-derived growth factor in unathletes female students. Koomesh. 2017;19:75-83.
  33. Biondo PD, Robbins SJ, Walsh JD, McCargar LJ, Harber VJ, Field CJ. A randomized controlled crossover trial of the effect of ginseng consumption on the immune response to moderate exercise in healthy sedentary men. Appl Physiol Nutr Metab. 2008;33:966-75. https://doi.org/10.1139/H08-080
  34. Kim SH, Park KS, Chang MJ, Sung JH. Effects of Panax ginseng extract on exercise-induced oxidative stress. J Sports Med Phys Fitness. 2005;45:178-82.
  35. Hayder M. Al-Kuraishy, Taissir Lateef Ali. Panax ginseng and ergogenic profile: randomized, placebo controlled study. J Adv Med Med Res. 2016;17:1.
  36. Kiefer D, Pantuso T. Panax ginseng. Am Fam Physician. 2003;68:1539-42.
  37. Arring NM, Millstine D, Marks LA, Nail LM. Ginseng as a treatment for fatigue: a systematic review. J Altern Complement Med. 2018;24:624-33. https://doi.org/10.1089/acm.2017.0361
  38. Jin TY, Rong PQ, Liang HY, Zhang PP, Zheng GQ, Lin Y. Clinical and preclinical systematic review of Panax ginseng C.A. Meyer and its compounds for fatigue. Front Pharmacol. 2020;11:1031. https://doi.org/10.3389/fphar.2020.01031
  39. Bucci LR. Selected herbals and human exercise performance. Am J Clin Nutr. 2000;72:624S-36S. https://doi.org/10.1093/ajcn/72.2.624S
  40. Sellami M, Slimeni O, Pokrywka A, Kuvacic Goran, Hayes LD, Milic M, Padulo J. Herbal medicine for sports: a review. J Int Soc Sports Nutr. 2018;15:14. https://doi.org/10.1186/s12970-018-0218-y
  41. Lu G, Liu Z, Wang X, Wang C. Recent advances in Panax ginseng C. A. Meyer as a herb for anti-fatigue: an effects and mechanisms review. Foods. 2021;10:1030. https://doi.org/10.3390/foods10051030
  42. Hargreaves M, Spriet LL. Exercise metabolism: fuels for the fire. Cold Spring Harb Perspect Med. 2018;8:a029744. https://doi.org/10.1101/cshperspect.a029744
  43. Chepurnov SA, Suleimanova EM, Guliaev MV, Abbasova KR, Pirogov IuA, Chepurnova NE. Neuroprotection in epilepsy. Usp Fiziol Nauk. 2012;43:55-71.
  44. Liu MY, Liu F, Gao YL, Yin JN, Yan WQ, Liu JG, Li HJ. Pharmacological activities of ginsenoside Rg5 (review). Exp Ther Med. 202;22:840. https://doi.org/10.3892/etm.2021.10272
  45. Marshall CJ. MAP kinase kinase kinase, MAP kinase kinase and MAP kinase. Curr Opin Genet Dev. 1994;4:82-9. https://doi.org/10.1016/0959-437X(94)90095-7
  46. Stewart A, Huang J, Fisher RA. RGS proteins in heart: brakes on the vagus. Front Physiol. 2012;3:95. https://doi.org/10.3389/fphys.2012.00095
  47. Filardo EJ, Quinn JA, Frackelton AR Jr, Bland KI. Estrogen action via the G protein-coupled receptor, GPR30: stimulation of adenylyl cyclase and cAMP-mediated attenuation of the epidermal growth factor receptor-to-MAPK signaling axis. Mol Endocrinol. 2002;16:70-84. https://doi.org/10.1210/mend.16.1.0758
  48. Zhang W, Elimban V, Nijjar MS, Gupta SK, Dhalla NS. Role of mitogen-activated protein kinase in cardiac hypertrophy and heart failure. Exp Clin Cardiol. 2003;8:173-83.
  49. Strniskova M, Barancik M, Ravingerova T. Mitogen-activated protein kinases and their role in regulation of cellular processes. Gen Physiol Biophys. 2002;21:231.