Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Systems-level mechanisms of action of Panax ginseng: a network pharmacological approach

  • Park, Sa-Yoon (Department of Physiology, College of Korean Medicine, Gachon University) ;
  • Park, Ji-Hun (Department of Physiology, College of Korean Medicine, Gachon University) ;
  • Kim, Hyo-Su (Department of Physiology, College of Korean Medicine, Gachon University) ;
  • Lee, Choong-Yeol (Department of Physiology, College of Korean Medicine, Gachon University) ;
  • Lee, Hae-Jeung (Department of Food and Nutrition, College of BioNano Technology, Gachon University) ;
  • Kang, Ki Sung (Department of Preventive Medicine, College of Korean Medicine, Gachon University) ;
  • Kim, Chang-Eop (Department of Physiology, College of Korean Medicine, Gachon University)
  • Received : 2017.08.18
  • Accepted : 2017.09.05
  • Published : 2018.01.15
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Abstract

Panax ginseng has been used since ancient times based on the traditional Asian medicine theory and clinical experiences, and currently, is one of the most popular herbs in the world. To date, most of the studies concerning P. ginseng have focused on specific mechanisms of action of individual constituents. However, in spite of many studies on the molecular mechanisms of P. ginseng, it still remains unclear how multiple active ingredients of P. ginseng interact with multiple targets simultaneously, giving the multidimensional effects on various conditions and diseases. In order to decipher the systems-level mechanism of multiple ingredients of P. ginseng, a novel approach is needed beyond conventional reductive analysis. We aim to review the systems-level mechanism of P. ginseng by adopting novel analytical framework-network pharmacology. Here, we constructed a compound-target network of P. ginseng using experimentally validated and machine learning-based prediction results. The targets of the network were analyzed in terms of related biological process, pathways, and diseases. The majority of targets were found to be related with primary metabolic process, signal transduction, nitrogen compound metabolic process, blood circulation, immune system process, cell-cell signaling, biosynthetic process, and neurological system process. In pathway enrichment analysis of targets, mainly the terms related with neural activity showed significant enrichment and formed a cluster. Finally, relative degrees analysis for the target-disease association of P. ginseng revealed several categories of related diseases, including respiratory, psychiatric, and cardiovascular diseases.

Keywords

References

  1. Park HJ, Kim DH, Park SJ, Kim JM, Ryu JH. Ginseng in traditional herbal prescriptions. J Ginseng Res 2012;36:225-41. https://doi.org/10.5142/jgr.2012.36.3.225
  2. Kuk YB, Kim SC, Park SD, Park SK, Seo BY, Seo YB, Shin SS, Lee SI, Lee JC, CH L. Formula study. Younglimsa. 1999 [in Korean].
  3. Xiang YZ, Shang HC, Gao XM, Zhang BL. A comparison of the ancient use of ginseng in traditional Chinese medicine with modern pharmacological experiments and clinical trials. Phytother Res 2008;22:851-8. https://doi.org/10.1002/ptr.2384
  4. Choi J, Kim TH, Choi TY, Lee MS. Ginseng for health care: a systematic review of randomized controlled trials in Korean literature. PLoS One 2013;8, e59978. https://doi.org/10.1371/journal.pone.0059978
  5. Lee HW, Lim HJ, Jun JH, Choi J, Lee MS. Ginseng for the treatment of hypertension: a systematic review and meta-analysis of double-blind, randomized, placebo-controlled trials. Curr Vasc Pharmacol 2017;15:549.
  6. Lee CH, Kim JH. A review on the medicinal potentials of ginseng and ginsenosides on cardiovascular diseases. J Ginseng Res 2014;38:161-6. https://doi.org/10.1016/j.jgr.2014.03.001
  7. Kim JH. Cardiovascular diseases and Panax ginseng: a review on molecular mechanisms and medical applications. J Ginseng Res 2012;36:16-26. https://doi.org/10.5142/jgr.2012.36.1.16
  8. Yuan CS, Wang CZ, Wicks SM, Qi LW. Chemical and pharmacological studies of saponins with a focus on American ginseng. J Ginseng Res 2010;34:160-7. https://doi.org/10.5142/jgr.2010.34.3.160
  9. Rhee YH, Ahn JH, Choe J, Kang KW, Joe C. Inhibition of mutagenesis and transformation by root extracts of Panax ginseng in vitro. Planta Med 1991;57: 125-8. https://doi.org/10.1055/s-2006-960047
  10. Attele AS, Wu JA, Yuan CS. Ginseng pharmacology: multiple constituents and multiple actions. Biochem Pharmacol 1999;58:1685-93. https://doi.org/10.1016/S0006-2952(99)00212-9
  11. Chen X, Lee TJ. Ginsenosides-induced nitric oxide-mediated relaxation of the rabbit corpus cavernosum. Br J Pharmacol 1995;115:15-8. https://doi.org/10.1111/j.1476-5381.1995.tb16313.x
  12. Lee MH, Jeong JH, Seo JW, Shin CG, Kim YS, In JG, Yang DC, Yi JS, Choi YE. Enhanced triterpene and phytosterol biosynthesis in Panax ginseng overexpressing squalene synthase gene. Plant Cell Physiol 2004;45:976-84. https://doi.org/10.1093/pcp/pch126
  13. Richter R, Basar S, Koch A, Konig WA. Three sesquiterpene hydrocarbons from the roots of Panax ginseng C.A. Meyer (Araliaceae). Phytochemistry 2005;66: 2708-13. https://doi.org/10.1016/j.phytochem.2005.09.012
  14. Kim JS. Investigation of phenolic, flavonoid, and vitamin contents in different parts of Korean Ginseng (Panax ginseng C.A. Meyer). Prev Nutr Food Sci 2016;21:263-70. https://doi.org/10.3746/pnf.2016.21.3.263
  15. Han BH, Park MH, Han YN, Woo LK. Alkaloidal components of Panax ginseng. Archives of Pharmacal Research 1986;9:21-3. https://doi.org/10.1007/BF02857702
  16. Huong NT, Matsumoto K, Kasai R, Yamasaki K, Watanabe H. In vitro antioxidant activity of Vietnamese ginseng saponin and its components. Biol Pharm Bull 1998;21:978-81. https://doi.org/10.1248/bpb.21.978
  17. Chang TK, Chen J, Benetton SA. In vitro effect of standardized ginseng extracts and individual ginsenosides on the catalytic activity of human CYP1A1, CYP1A2, and CYP1B1. Drug Metab Dispos 2002;30:378-84. https://doi.org/10.1124/dmd.30.4.378
  18. Rimar S, Lee-Mengel M, Gillis CN. Pulmonary protective and vasodilator effects of a standardized Panax ginseng preparation following artificial gastric digestion. Pulm Pharmacol 1996;9:205-9. https://doi.org/10.1006/pulp.1996.0025
  19. Hopkins AL. Network pharmacology: the next paradigm in drug discovery. Nat Chem Biol 2008;4:682-90. https://doi.org/10.1038/nchembio.118
  20. Ru J, Li P, Wang J, Zhou W, Li B, Huang C, Li P, Guo Z, Tao W, Yang Y, et al. 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
  21. Mi H, Huang X, Muruganujan A, Tang H, Mills C, Kang D, Thomas PD. PANTHER version 11: expanded annotation data from Gene Ontology and Reactome pathways, and data analysis tool enhancements. Nucleic Acids Res 2017;45: D183-9. https://doi.org/10.1093/nar/gkw1138
  22. Mi H, Muruganujan A, Casagrande JT, Thomas PD. Large-scale gene function analysis with the PANTHER classification system. Nat Protoc 2013;8:1551-66. https://doi.org/10.1038/nprot.2013.092
  23. Elyakov G, Strigina L, Uvarova N, Vaskovsky V, Dzizenko A, Kochetkov N. Glycosides from ginseng roots. Tetrahedron Letters 1964;5:3591-7. https://doi.org/10.1016/S0040-4039(01)89378-3
  24. Tansakul P, Shibuya M, Kushiro T, Ebizuka Y. Dammarenediol-II synthase, the first dedicated enzyme for ginsenoside biosynthesis, in Panax ginseng. FEBS Lett 2006;580:5143-9. https://doi.org/10.1016/j.febslet.2006.08.044
  25. Shin BK, Kwon SW, Park JH. Chemical diversity of ginseng saponins from Panax ginseng. J Ginseng Res 2015;39:287-98. https://doi.org/10.1016/j.jgr.2014.12.005
  26. Hasegawa H, Suzuki R, Nagaoka T, Tezuka Y, Kadota S, Saiki I. Prevention of growth and metastasis of murine melanoma through enhanced natural-killer cytotoxicity by fatty acid-conjugate of protopanaxatriol. Biol Pharm Bull 2002;25:861-6. https://doi.org/10.1248/bpb.25.861
  27. Tawab MA, Bahr U, Karas M, Wurglics M, Schubert-Zsilavecz M. Degradation of ginsenosides in humans after oral administration. Drug Metab Dispos 2003;31:1065-71. https://doi.org/10.1124/dmd.31.8.1065
  28. Ling WH, Jones PJ. Dietary phytosterols: a review of metabolism, benefits and side effects. Life Sci 1995;57:195-206. https://doi.org/10.1016/0024-3205(95)00263-6
  29. Iwabuchi H, Kato N, Yoshikura M. Studies on the sesquiterpenoids of Panax ginseng C. A. Meyer. IV. Chem Pharm Bull (Tokyo) 1990;38:1405-7. https://doi.org/10.1248/cpb.38.1405
  30. Kumar S, Pandey AK. Chemistry and biological activities of flavonoids: an overview. Sci World J 2013;2013, 162750.
  31. Takahashi M, Yoshikura M. Studies on the components of Panax ginseng C.A. Meyer. V. On the structure of a new acetylene derivative "Panaxynol" (3). Synthesis of 1,9-(cis)-heptadecadiene-4,6-diyn-3-ol. Yakugaku Zasshi 1966;86:1053-6 [in Japanese]. https://doi.org/10.1248/yakushi1947.86.11_1053
  32. Matsunaga H, Katano M, Yamamoto H, Fujito H, Mori M, Takata K. Cytotoxic activity of polyacetylene compounds in Panax ginseng C. A. Meyer. Chem Pharm Bull (Tokyo) 1990;38:3480-2. https://doi.org/10.1248/cpb.38.3480
  33. Kong Y-H, Lee Y-C, Choi S-Y. Neuroprotective and anti-inflammatory effects of phenolic compounds in Panax ginseng CA Meyer. J Ginseng Res 2009;33: 111-4. https://doi.org/10.5142/JGR.2009.33.2.111
  34. Lee LS, Cho CW, Hong HD, Lee YC, Choi UK, Kim YC. Hypolipidemic and antioxidant properties of phenolic compound-rich extracts from white ginseng (Panax ginseng) in cholesterol-fed rabbits. Molecules 2013;18:12548-60. https://doi.org/10.3390/molecules181012548
  35. Zhou W, Wang J, Wu Z, Huang C, Lu A, Wang Y. Systems pharmacology exploration of botanic drug pairs reveals the mechanism for treating different diseases. Sci Rep 2016;6, 36985. https://doi.org/10.1038/srep36985
  36. Yu H, Chen J, Xu X, Li Y, Zhao H, Fang Y, Li X, Zhou W, Wang W, Wang Y. A systematic prediction of multiple drug-target interactions from chemical, genomic, and pharmacological data. PLoS One 2012;7, e37608. https://doi.org/10.1371/journal.pone.0037608
  37. Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 2003;13:2498-504. https://doi.org/10.1101/gr.1239303
  38. Chen EY, Tan CM, Kou Y, Duan Q, Wang Z, Meirelles GV, Clark NR, Ma'ayan A. Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinformatics 2013;14:128. https://doi.org/10.1186/1471-2105-14-128
  39. Kanehisa M, Goto S, Kawashima S, Nakaya A. The KEGG databases at GenomeNet. Nucleic Acids Res 2002;30:42-6. https://doi.org/10.1093/nar/30.1.42
  40. Jung JH, Kang IG, Kim DY, Hwang YJ, Kim ST. The effect of Korean red ginseng on allergic inflammation in a murine model of allergic rhinitis. J Ginseng Res 2013;37:167-75. https://doi.org/10.5142/jgr.2013.37.167
  41. Babayigit A, Olmez D, Karaman O, Bagriyanik HA, Yilmaz O, Kivcak B, Erbil G, Uzuner N. Ginseng ameliorates chronic histopathologic changes in a murine model of asthma. Allergy Asthma Proc 2008;29:493-8. https://doi.org/10.2500/aap.2008.29.3137
  42. Lim CY, Moon JM, Kim BY, Lim SH, Lee GS, Yu HS, Cho SI. Comparative study of Korean White Ginseng and Korean Red Ginseng on efficacies of OVA-induced asthma model in mice. J Ginseng Res 2015;39:38-45. https://doi.org/10.1016/j.jgr.2014.07.004
  43. Kim DY, Yang WM. Panax ginseng ameliorates airway inflammation in an ovalbumin-sensitized mouse allergic asthma model. J Ethnopharmacol 2011;136:230-5. https://doi.org/10.1016/j.jep.2011.04.048
  44. Tran TV, Shin EJ, Ko SK, Nam Y, Chung YH, Jeong JH, Jang CG, Nah SY, Yamada K, Nabeshima T, et al. Mountain-cultivated ginseng attenuates phencyclidine-induced abnormal behaviors in mice by positive modulation of glutathione in the prefrontal cortex of mice. J Med Food 2016;19:961-9. https://doi.org/10.1089/jmf.2016.3751
  45. Dang H, Sun L, Liu X, Peng B, Wang Q, Jia W, Chen Y, Pan A, Xiao P. Preventive action of Kai Xin San aqueous extract on depressive-like symptoms and cognition deficit induced by chronic mild stress. Exp Biol Med (Maywood) 2009;234:785-93. https://doi.org/10.3181/0812-RM-354
  46. Zhu KY, Mao QQ, Ip SP, Choi RC, Dong TT, Lau DT, Tsim KW. A standardized Chinese herbal decoction, Kai-Xin-San, restores decreased levels of neurotransmitters and neurotrophic factors in the brain of chronic stressinduced depressive rats. Evid Based Complement Alternat Med 2012;2012, 149256.
  47. Yan L, Hu Q, Mak MS, Lou J, Xu SL, Bi CW, Zhu Y, Wang H, Dong TT, Tsim KW. A Chinese herbal decoction, reformulated from Kai-Xin-San, relieves the depression-like symptoms in stressed rats and induces neurogenesis in cultured neurons. Sci Rep 2016;6, 30014. https://doi.org/10.1038/srep30014
  48. Zhu Y, Duan X, Cheng X, Cheng X, Li X, Zhang L, Liu P, Su S, Duan JA, Dong TT, et al. Kai-Xin-San, a standardized traditional Chinese medicine formula, upregulates the expressions of synaptic proteins on hippocampus of chronic mild stress induced depressive rats and primary cultured rat hippocampal neuron. J Ethnopharmacol 2016;193:423-32. https://doi.org/10.1016/j.jep.2016.09.037
  49. Zhu Y, Chao C, Duan X, Cheng X, Liu P, Su S, Duan J, Dong TT, Tsim KW. Kai-Xin-San series formulae alleviate depressive-like behaviors on chronic mild stressed mice via regulating neurotrophic factor system on hippocampus. Sci Rep 2017;7, 1467. https://doi.org/10.1038/s41598-017-01561-2
  50. Yan S, You ZL, Zhao QY, Peng C, He G, Gou XJ, Lin B. Antidepressant-like effects of Sanyuansan in the mouse forced swim test, tail suspension test, and chronic mild stress model. Kaohsiung J Med Sci 2015;31:605-12. https://doi.org/10.1016/j.kjms.2015.10.009
  51. Zhang K, Wang F, Yang JY, Wang LJ, Pang HH, Su GY, Ma J, Song SJ, Xiong ZL, Wu CF. Analysis of main constituents and mechanisms underlying antidepressant-like effects of Xiaochaihutang in mice. J Ethnopharmacol 2015;175:48-57. https://doi.org/10.1016/j.jep.2015.08.031
  52. Kuribara H, Tomioka H, Takahashi R, Onozato K, Murohashi N, Numajiri T, Iwata H, Koya S. An antidepressant effect of Sho-ju-sen, a Japanese herbal medicine, assessed by learned helplessness model in mice. Phytother Res 2004;18:173-6. https://doi.org/10.1002/ptr.1412
  53. Lee KJ, Ji GE. The effect of fermented red ginseng on depression is mediated by lipids. Nutr Neurosci 2014;17:7-15. https://doi.org/10.1179/1476830513Y.0000000059
  54. Jeong HG, Ko YH, Oh SY, Han C, Kim T, Joe SH. Effect of Korean Red Ginseng as an adjuvant treatment for women with residual symptoms of major depression. Asia Pac Psychiatry 2015;7:330-6. https://doi.org/10.1111/appy.12169
  55. Kim YO, Lee HY, Won H, Nah SS, Lee HY, Kim HK, Kwon JT, Kim HJ. Influence of Panax ginseng on the offspring of adult rats exposed to prenatal stress. Int J Mol Med 2015;35:103-9. https://doi.org/10.3892/ijmm.2014.2003
  56. Hong SY, Kim JY, Ahn HY, Shin JH, Kwon O. Panax ginseng extract rich in ginsenoside protopanaxatriol attenuates blood pressure elevation in spontaneously hypertensive rats by affecting the Akt-dependent phosphorylation of endothelial nitric oxide synthase. J Agric Food Chem 2012;60:3086-91. https://doi.org/10.1021/jf204447y
  57. Lei Y, Tao LL, Wang GL. Effect of extracts from Panax ginseng, Panax notoginseng, and Ligusticum chuanxiong on vascular smooth muscle cells of aging and hypertension rats. Zhongguo Zhong Xi Yi Jie He Za Zhi 2012;32:1374-9 [in Chinese].
  58. Zhou W, Chai H, Lin PH, Lumsden AB, Yao Q, Chen CJ. Molecular mechanisms and clinical applications of ginseng root for cardiovascular disease. Med Sci Monit 2004;10:RA187-R192.
  59. Rhee MY, Kim YS, Bae JH, Nah DY, Kim YK, Lee MM, Kim HY. Effect of Korean red ginseng on arterial stiffness in subjects with hypertension. J Altern Complement Med 2011;17:45-9. https://doi.org/10.1089/acm.2010.0065
  60. Jeon BH, Kim CS, Kim HS, Park JB, Nam KY, Chang SJ. Effect of Korean red ginseng on blood pressure and nitric oxide production. Acta Pharmacol Sin 2000;21:1095-100.
  61. Jeon BH, Kim CS, Park KS, Lee JW, Park JB, Kim KJ, Kim SH, Chang SJ, Nam KY. Effect of Korea red ginseng on the blood pressure in conscious hypertensive rats. Gen Pharmacol 2000;35:135-41. https://doi.org/10.1016/S0306-3623(01)00096-9
  62. Kang SY, Schini-Kerth VB, Kim ND. Ginsenosides of the protopanaxatriol group cause endothelium-dependent relaxation in the rat aorta. Life Sci 1995;56:1577-86. https://doi.org/10.1016/0024-3205(95)00124-O
  63. Kim ND, Kang SY, Schini VB. Ginsenosides evoke endothelium-dependent vascular relaxation in rat aorta. Gen Pharmacol 1994;25:1071-7. https://doi.org/10.1016/0306-3623(94)90121-X
  64. Shin W, Yoon J, Oh GT, Ryoo S. Korean red ginseng inhibits arginase and contributes to endothelium dependent vasorelaxation through endothelial nitric oxide synthase coupling. J Ginseng Res 2013;37:64-73. https://doi.org/10.5142/jgr.2013.37.64
  65. Lee JJ, Kwon HK, Jung IH, Cho YB, Kim KJ, Kim JL. Anti-cancer activities of ginseng extract fermented with Phellinus linteus. Mycobiology 2009;37:21-7. https://doi.org/10.4489/MYCO.2009.37.1.021
  66. Hwang SH, Lee BH, Choi SH, Kim HJ, Won KJ, Lee HM, Rhim H, Kim HC, Nah SY. Effects of gintonin on the proliferation, migration, and tube formation of human umbilical-vein endothelial cells: involvement of lysophosphatidic-acid receptors and vascular-endothelial-growth-factor signaling. J Ginseng Res 2016;40:325-33. https://doi.org/10.1016/j.jgr.2015.10.002
  67. Yue PY, Wong DY, Wu PK, Leung PY, Mak NK, Yeung HW, Liu L, Cai Z, Jiang ZH, Fan TP, et al. The angiosuppressive effects of 20(R)- ginsenoside Rg3. Biochem Pharmacol 2006;72:437-45. https://doi.org/10.1016/j.bcp.2006.04.034
  68. Kim JW, Jung SY, Kwon YH, Lee JH, Lee YM, Lee BY, Kwon SM. Ginsenoside Rg3 attenuates tumor angiogenesis via inhibiting bioactivities of endothelial progenitor cells. Cancer Biol Ther 2012;13:504-15. https://doi.org/10.4161/cbt.19599
  69. Choi KS, Song H, Kim EH, Choi JH, Hong H, Han YM, Hahm KB. Inhibition of hydrogen sulfide-induced angiogenesis and inflammation in vascular endothelial cells: potential mechanisms of gastric cancer prevention by Korean Red Ginseng. J Ginseng Res 2012;36:135-45. https://doi.org/10.5142/jgr.2012.36.2.135
  70. Zhou H, Hou SZ, Luo P, Zeng B, Wang JR, Wong YF, Jiang ZH, Liu L. Ginseng protects rodent hearts from acute myocardial ischemia-reperfusion injury through GR/ER-activated RISK pathway in an endothelial NOS-dependent mechanism. J Ethnopharmacol 2011;135:287-98. https://doi.org/10.1016/j.jep.2011.03.015
  71. Kim TH, Lee SM. The effects of ginseng total saponin, panaxadiol and panaxatriol on ischemia/reperfusion injury in isolated rat heart. Food Chem Toxicol 2010;48:1516-20. https://doi.org/10.1016/j.fct.2010.03.018
  72. Aravinthan A, Kim JH, Antonisamy P, Kang CW, Choi J, Kim NS, Kim JH. Ginseng total saponin attenuates myocardial injury via anti-oxidative and anti-inflammatory properties. J Ginseng Res 2015;39:206-12. https://doi.org/10.1016/j.jgr.2014.12.001
  73. Luo P, Dong G, Liu L, Zhou H. The long-term consumption of ginseng extract reduces the susceptibility of intermediate-aged hearts to acute ischemia reperfusion injury. PLoS One 2015;10, e0144733. https://doi.org/10.1371/journal.pone.0144733
  74. Van Kampen JM, Baranowski DB, Shaw CA, Kay DG. Panax ginseng is neuroprotective in a novel progressive model of Parkinson's disease. Exp Gerontol 2014;50:95-105. https://doi.org/10.1016/j.exger.2013.11.012
  75. Hu S, Han R, Mak S, Han Y. Protection against 1-methyl-4-phenylpyridinium ion (MPP+)-induced apoptosis by water extract of ginseng (Panax ginseng C.A. Meyer) in SH-SY5Y cells. J Ethnopharmacol 2011;135:34-42. https://doi.org/10.1016/j.jep.2011.02.017
  76. Nah JJ, Hahn JH, Chung S, Choi S, Kim YI, Nah SY. Effect of ginsenosides, active components of ginseng, on capsaicin-induced pain-related behavior. Neuropharmacology 2000;39:2180-4. https://doi.org/10.1016/S0028-3908(00)00048-4
  77. Mogil JS, Shin YH, McCleskey EW, Kim SC, Nah SY. Ginsenoside Rf, a trace component of ginseng root, produces antinociception in mice. Brain Res 1998;792:218-28. https://doi.org/10.1016/S0006-8993(98)00133-4
  78. Yin H, Park SA, Park SJ, Han SK. Korean Red Ginseng extract activatesnon-NMDA glutamate and GABAA receptors on the substantia gelatinosa neurons of the trigeminal subnucleus caudalis in mice. J Ginseng Res 2011;35:219-25. https://doi.org/10.5142/jgr.2011.35.2.219
  79. Lee JH, Lee JH, Lee YM, Kim PN, Jeong CS. Potential analgesic and antiinflammatory activities of Panax ginseng head butanolic fraction in animals. Food Chem Toxicol 2008;46:3749-52. https://doi.org/10.1016/j.fct.2008.09.055
  80. Wang Y, Chen Y, Xu H, Luo H, Jiang R. Analgesic effects of glycoproteins from Panax ginseng root in mice. J Ethnopharmacol 2013;148:946-50. https://doi.org/10.1016/j.jep.2013.05.049
  81. Suzuki T, Yamamoto A, Ohsawa M, Motoo Y, Mizukami H, Makino T. Effect of ninjin'yoeito and ginseng extracts on oxaliplatin-induced neuropathies in mice. J Nat Med 2017;71:757-64. https://doi.org/10.1007/s11418-017-1113-6

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