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Role of ginsenosides, the main active components of Panax ginseng, in inflammatory responses and diseases

  • Kim, Ji Hye (Department of Genetic Engineering, Sungkyunkwan University) ;
  • Yi, Young-Su (Department of Pharmaceutical Engineering, Cheongju University) ;
  • Kim, Mi-Yeon (School of Systems Biomedical Science, Soongsil University) ;
  • Cho, Jae Youl (Department of Genetic Engineering, Sungkyunkwan University)
  • Received : 2016.07.12
  • Accepted : 2016.08.09
  • Published : 2017.10.15

Abstract

Panax ginseng is one of the most universally used herbal medicines in Asian and Western countries. Most of the biological activities of ginseng are derived from its main constituents, ginsenosides. Interestingly, a number of studies have reported that ginsenosides and their metabolites/derivatives-including ginsenoside (G)-Rb1, compound K, G-Rb2, G-Rd, G-Re, G-Rg1, G-Rg3, G-Rg5, G-Rh1, G-Rh2, and G-Rp1-exert anti-inflammatory activities in inflammatory responses by suppressing the production of proinflammatory cytokines and regulating the activities of inflammatory signaling pathways, such as nuclear factor-${\kappa}B$ and activator protein-1. This review discusses recent studies regarding molecular mechanisms by which ginsenosides play critical roles in inflammatory responses and diseases, and provides evidence showing their potential to prevent and treat inflammatory diseases.

Acknowledgement

Supported by : Korean Ginseng Corporation (KGC)

References

  1. Abbas AK, Lichtman AH, Pillai S. Basic immunology: functions and disorders of the immune system. Elsevier Health Sciences; 2012.
  2. Medzhitov R. Recognition of microorganisms and activation of the immune response. Nature 2007;449:819-26. https://doi.org/10.1038/nature06246
  3. Lodish H, Berk A, Zipursky S. Molecular cell biology. 4th ed. New York: W.H. Freeman; 2000.
  4. Janeway CA, Travers P, Walport M, Shlomchik MJ. Immunobiology: the immune system in health and disease. New York: Garland; 2001.
  5. Medzhitov R, Janeway Jr CA. Innate immune recognition and control of adaptive immune responses. Semin Immunol 1998;10:351-3. https://doi.org/10.1006/smim.1998.0136
  6. Rus H, Cudrici C, Niculescu F. The role of the complement system in innate immunity. Immunol Res 2005;33:103-12. https://doi.org/10.1385/IR:33:2:103
  7. Janeway CA, Travers P, Walport M, Capra JD. Immunobiology: the immune system in health and disease. New York: Garland; 2005.
  8. Abbas AK, Murphy KM, Sher A. Functional diversity of helper T lymphocytes. Nature 1996;383:787-93. https://doi.org/10.1038/383787a0
  9. McHeyzer-Williams L, Malherbe L, McHeyzer-Williams M. Helper T cell-regulated B cell immunity. Curr Top Microbiol Immunol 2006;311:59-83.
  10. Hong BN, Ji MG, Kang TH. The efficacy of red ginseng in type 1 and type 2 diabetes in animals. Evidence Based Complement Alternat Med 2013;2013:593181.
  11. Helmes S. Cancer prevention and therapeutics: Panax ginseng. Altern Med Rev 2004;9:259-75.
  12. Ernst E. Complementary/alternative medicine for hypertension: a mini-review. Wiener Med Wochenschr 2005;155:386-91. https://doi.org/10.1007/s10354-005-0205-1
  13. Jeong CS. Effect of butanol fraction of Panax ginseng head on gastric lesion and ulcer. Arch Pharm Res 2002;25:61-6. https://doi.org/10.1007/BF02975263
  14. Kiefer D, Pantuso T. Panax ginseng. Am Fam Physician 2003;68:1539-44.
  15. Yun TK. Brief introduction of Panax ginseng CA Meyer. J Korean Med Sci 2001;16:S3. https://doi.org/10.3346/jkms.2001.16.S.S3
  16. Gillis CN. Panax ginseng pharmacology: a nitric oxide link? Biochem Pharmacol 1997;54:1-8. https://doi.org/10.1016/S0006-2952(97)00193-7
  17. Attele AS, Wu JA, Yuan C-S. Ginseng pharmacology: multiple constituents and multiple actions. Biochem Pharmacol 1999;58:1685-93. https://doi.org/10.1016/S0006-2952(99)00212-9
  18. Hasegawa H. Proof of the mysterious efficacy of ginseng: basic and clinical trials: metabolic activation of ginsenoside: deglycosylation by intestinal bacteria and esterification with fatty acid. J Pharmacol Sci 2004;95:153-7. https://doi.org/10.1254/jphs.FMJ04001X4
  19. Chang-Xiao L, Pei-Gen X. Recent advances on ginseng research in China. J Ethnopharmacol 1992;36:27-38. https://doi.org/10.1016/0378-8741(92)90057-X
  20. Ferrero-Miliani L, Nielsen O, Andersen P, Girardin S. Chronic inflammation: importance of NOD2 and NALP3 in interleukin-$1{\beta}$ generation. Clin Exp Immunol 2007;147:227-35.
  21. Medzhitov R. Origin and physiological roles of inflammation. Nature 2008;454:428-35. https://doi.org/10.1038/nature07201
  22. Lange C, Hemmrich G, Klostermeier UC, Lopez-Quintero JA, Miller DJ, Rahn T, Weiss Y, Bosch TC, Rosenstiel P. Defining the origins of the NOD-like receptor system at the base of animal evolution. Mol Biol Evol 2011;28:1687-702. https://doi.org/10.1093/molbev/msq349
  23. Proell M, Riedl SJ, Fritz JH, Rojas AM, Schwarzenbacher R. The Nod-like receptor (NLR) family: a tale of similarities and differences. PLoS One 2008;3:e2119. https://doi.org/10.1371/journal.pone.0002119
  24. Roach JC, Glusman G, Rowen L, Kaur A, Purcell MK, Smith KD, Hood LE, Aderem A. The evolution of vertebrate Toll-like receptors. Proc Natl Acad Sci U S A 2005;102:9577-82. https://doi.org/10.1073/pnas.0502272102
  25. Martinon F, Mayor A, Tschopp J. The inflammasomes: guardians of the body. Annu Rev Immunol 2009;27:229-65. https://doi.org/10.1146/annurev.immunol.021908.132715
  26. Coussens LM, Werb Z. Inflammation and cancer. Nature 2002;420:860-7. https://doi.org/10.1038/nature01322
  27. Gonzalez-Chavez A, Elizondo-Argueta S, Gutierrez-Reyes G, Leon-Pedroza JI. Pathophysiological implications between chronic inflammation and the development of diabetes and obesity. Cir Cir 2011;79:209-16.
  28. Tracy R. Emerging relationships of inflammation, cardiovascular disease and chronic diseases of aging. Int J Obes Relat Metab Disord 2003;27.
  29. Wyss-Coray T. Inflammation in Alzheimer disease: driving force, bystander or beneficial response? Nat Med 2006;12:1005-15.
  30. Rhule A, Navarro S, Smith JR, Shepherd DM. Panax notoginseng attenuates LPS-induced pro-inflammatory mediators in RAW264.7 cells. J Ethnopharmacol 2006;106:121-8. https://doi.org/10.1016/j.jep.2005.12.012
  31. Cho JY, Yoo ES, Baik KU, Park MH, Han BH. In vitro inhibitory effect of protopanaxadiol ginsenosides on tumor necrosis factor (TNF)-alpha production and its modulation by known TNF-alpha antagonists. Planta Med 2001;67:213-8. https://doi.org/10.1055/s-2001-12005
  32. Joh E-H, Lee I-A, Jung I-H, Kim D-H. Ginsenoside Rb1 and its metabolite compound K inhibit IRAK-1 activation-the key step of inflammation. Biochem Pharmacol 2011;82:278-86. https://doi.org/10.1016/j.bcp.2011.05.003
  33. Wood AJ, Eastell R. Treatment of postmenopausal osteoporosis. N Engl J Med 1998;338:736-46. https://doi.org/10.1056/NEJM199803123381107
  34. Ginaldi L, Di Benedetto MC, De Martinis M. Osteoporosis, inflammation and ageing. Immun Ageing 2005;2:1. https://doi.org/10.1186/1742-4933-2-1
  35. Spector T, Hall G, McCloskey E, Kanis J. Risk of vertebral fracture in women with rheumatoid arthritis. BMJ 1993;306:558. https://doi.org/10.1136/bmj.306.6877.558
  36. Gough A, Emery P, Holder R, Lilley J, Eyre S. Generalised bone loss in patients with early rheumatoid arthritis. Lancet 1994;344:23-7. https://doi.org/10.1016/S0140-6736(94)91049-9
  37. Bernstein CN, Blanchard JF, Leslie W, Wajda A, Yu BN. The incidence of fracture among patients with inflammatory bowel disease: a population-based cohort study. Ann Intern Med 2000;133:795-9. https://doi.org/10.7326/0003-4819-133-10-200011210-00012
  38. Schoon EJ, Blok BM, Geerling BJ, Russel MG, Stockbrugger RW, Brummer RJM. Bone mineral density in patients with recently diagnosed inflammatory bowel disease. Gastroenterology 2000;119:1203-8. https://doi.org/10.1053/gast.2000.19280
  39. Bultink IE, Lems WF, Kostense PJ, Dijkmans BA, Voskuyl AE. Prevalence of and risk factors for low bone mineral density and vertebral fractures in patients with systemic lupus erythematosus. Arthritis Rheum 2005;52:2044-50. https://doi.org/10.1002/art.21110
  40. Mundy GR. Osteoporosis and inflammation. Nutr Rev 2007;65:S147-51. https://doi.org/10.1301/nr.2007.dec.S147-S151
  41. Teitelbaum SL. Osteoclasts: what do they do and how do they do it? Am J Pathol 2007;170:427-35. https://doi.org/10.2353/ajpath.2007.060834
  42. Cheng B, Li J, Du J, Lv X, Weng L, Ling C. Ginsenoside Rb1 inhibits osteoclastogenesis by modulating $NF-{\kappa}B$ and MAPKs pathways. Food Chem Toxicol 2012;50:1610-5. https://doi.org/10.1016/j.fct.2012.02.019
  43. Cuong TT, Yang C-S, Yuk J-M, Lee H-M, Ko S-R, Cho B-G, Jo E-K. Glucocorticoid receptor agonist compound K regulates Dectin-1-dependent inflammatory signaling through inhibition of reactive oxygen species. Life Sci 2009;85:625-33. https://doi.org/10.1016/j.lfs.2009.08.014
  44. Park J-S, Shin JA, Jung J-S, Hyun J-W, Van Le TK, Kim D-H, Park E-M, Kim H-S. Anti-inflammatory mechanism of compound K in activated microglia and its neuroprotective effect on experimental stroke in mice. J Pharmacol Exp Ther 2012;341:59-67. https://doi.org/10.1124/jpet.111.189035
  45. Park E-K, Shin Y-W, Lee H-U, Kim S-S, Lee Y-C, Lee B-Y, Kim D-H. Inhibitory effect of ginsenoside Rb1 and compound K on NO and prostaglandin E2 biosyntheses of RAW264.7 cells induced by lipopolysaccharide. Biol Pharmacol Bull 2005;28:652-6. https://doi.org/10.1248/bpb.28.652
  46. Lee J-Y, Shin J-W, Chun K-S, Park K-K, Chung W-Y, Bang Y-J, Sung J-H, Surh Y-J. Antitumor promotional effects of a novel intestinal bacterial metabolite (IH-901) derived from the protopanaxadiol-type ginsenosides in mouse skin. Carcinogenesis 2005;26:359-67.
  47. Li J, Zhong W, Wang W, Hu S, Yuan J, Zhang B, Hu T, Song G. Ginsenoside metabolite compound K promotes recovery of dextran sulfate sodium-induced colitis and inhibits inflammatory responses by suppressing $NF-{\kappa}B$ activation. PLoS One 2014;9:e87810. https://doi.org/10.1371/journal.pone.0087810
  48. Yang CS, Ko SR, Cho BG, Shin DM, Yuk JM, Li S, Kim JM, Evans RM, Jung JS, Song DK. The ginsenoside metabolite compound K, a novel agonist of glucocorticoid receptor, induces tolerance to endotoxin-induced lethal shock. J Cell Mol Med 2008;12:1739-53. https://doi.org/10.1111/j.1582-4934.2007.00181.x
  49. Wu CF, Bi XL, Yang JY, Zhan JY, Dong YX, Wang JH, Wang JM, Zhang R, Li X. Differential effects of ginsenosides on NO and $TNF-{\alpha}$ production by LPS-activated N9 microglia. Int Immunopharmacol 2007;7:313-20. https://doi.org/10.1016/j.intimp.2006.04.021
  50. Ye R, Yang Q, Kong X, Han J, Zhang X, Zhang Y, Li P, Liu J, Shi M, Xiong L. Ginsenoside Rd attenuates early oxidative damage and sequential inflammatory response after transient focal ischemia in rats. Neurochem Int 2011;58:391-8. https://doi.org/10.1016/j.neuint.2010.12.015
  51. Kim DH, Chung JH, Yoon JS, Ha YM, Bae S, Lee EK, Jung KJ, Kim MS, Kim YJ, Kim MK. Ginsenoside Rd inhibits the expressions of iNOS and COX-2 by suppressing $NF-{\kappa}B$ in LPS-stimulated RAW264.7 cells and mouse liver. J Ginseng Res 2013;37:54-63. https://doi.org/10.5142/jgr.2013.37.54
  52. Lee I-A, Hyam SR, Jang S-E, Han MJ, Kim D-H. Ginsenoside Re ameliorates inflammation by inhibiting the binding of lipopolysaccharide to TLR4 on macrophages. J Agric Food Chem 2012;60:9595-602. https://doi.org/10.1021/jf301372g
  53. Olson JK, Miller SD. Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs. The J Immunol 2004;173:3916-24. https://doi.org/10.4049/jimmunol.173.6.3916
  54. McGeer P, Itagaki S, Boyes B, McGeer E. Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson's and Alzheimer's disease brains. Neurology 1988;38:1285-91. https://doi.org/10.1212/WNL.38.8.1285
  55. Lee K-W, Jung SY, Choi S-M, Yang EJ. Effects of ginsenoside Re on LPS-induced inflammatory mediators in BV2 microglial cells. BMC Complement Altern Med 2012;12:196. https://doi.org/10.1186/1472-6882-12-S1-P196
  56. Hu J-F, Song X-Y, Chu S-F, Chen J, Ji H-J, Chen X-Y, Yuan Y-H, Han N, Zhang J-T, Chen N-H. Inhibitory effect of ginsenoside Rg1 on lipopolysaccharide-induced microglial activation in mice. Brain Res 2011;1374:8-14. https://doi.org/10.1016/j.brainres.2010.11.069
  57. Zong Y, Ai Q-L, Zhong L-M, Dai J-N, Yang P, He Y, Sun J, Ling E-A, Lu D. Ginsenoside Rg1 attenuates lipopolysaccharide-induced inflammatory responses via the phospholipase $C-{\gamma}1$ signaling pathway in murine BV-2 microglial cells. Curr Med Chem 2012;19:770-9. https://doi.org/10.2174/092986712798992066
  58. Sun X-C, Ren X-F, Chen L, Gao X-Q, Xie J-X, Chen W-F. Glucocorticoid receptor is involved in the neuroprotective effect of ginsenoside Rg1 against inflammation-induced dopaminergic neuronal degeneration in substantia nigra. J Steroid Biochem Mol Biol 2016;155:94-103. https://doi.org/10.1016/j.jsbmb.2015.09.040
  59. Wang Y, Liu Y, Zhang X-Y, Xu L-H, Ouyang D-Y, Liu K-P, Pan H, He J, He X-H. Ginsenoside Rg1 regulates innate immune responses in macrophages through differentially modulating the $NF-{\kappa}B$ and PI3K/Akt/mTOR pathways. Int Immunopharmacol 2014;23:77-84. https://doi.org/10.1016/j.intimp.2014.07.028
  60. Gao Y, Chu S, Li J, Li J, Zhang Z, Xia C, Heng Y, Zhang M, Hu J, Wei G. Anti-inflammatory function of ginsenoside Rg1 on alcoholic hepatitis through glucocorticoid receptor related nuclear factor-kappa B pathway. J Ethnopharmacol 2015;173:231-40. https://doi.org/10.1016/j.jep.2015.07.020
  61. Lee S-Y, Jeong J-J, Eun S-H, Kim D-H. 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
  62. Tao T, Chen F, Bo L, Xie Q, Yi W, Zou Y, Hu B, Li J, Deng X. Ginsenoside Rg1 protects mouse liver against ischemia-reperfusion injury through anti-inflammatory and anti-apoptosis properties. J Surg Res 2014;191:231-8. https://doi.org/10.1016/j.jss.2014.03.067
  63. Guo Y, Yang T, Lu J, Li S, Wan L, Long D, Li Q, Feng L, Li Y. Rb1 postconditioning attenuates liver warm ischemia-reperfusion injury through ROS-NO-HIF pathway. Life Sci 2011;88:598-605. https://doi.org/10.1016/j.lfs.2011.01.022
  64. Yang Y, Li X, Zhang L, Liu L, Jing G, Cai H. Ginsenoside Rg1 suppressed inflammation and neuron apoptosis by activating $PPAR{\gamma}/HO-1$ in hippocampus in rat model of cerebral ischemia-reperfusion injury. Int J Clin Exp Pathol 2015;8:2484.
  65. Xie C-L, Li J-H, Wang W-W, Zheng G-Q, Wang L-X. Neuroprotective effect of ginsenoside-Rg1 on cerebral ischemia/reperfusion injury in rats by down-regulating protease-activated receptor-1 expression. Life Sci 2015;121:145-51. https://doi.org/10.1016/j.lfs.2014.12.002
  66. Li G, Qian W, Zhao C. Analyzing the anti-ischemia-reperfusion injury effects of ginsenoside Rb1 mediated through the inhibition of $p38{\alpha}$ MAPK. Can J Physiol Pharmacol 2015;94:97-103.
  67. Joo SS, Yoo YM, Ahn BW, Nam SY, Kim Y-B, Hwang KW, Lee DI. Prevention of inflammation-mediated neurotoxicity by Rg3 and its role in microglial activation. Biol Pharm Bull 2008;31:1392-6. https://doi.org/10.1248/bpb.31.1392
  68. Lee B, Sur B, Park J, Kim S-H, Kwon S, Yeom M, Shim I, Lee H, Hahm D-H. Ginsenoside rg3 alleviates lipopolysaccharide-induced learning and memory impairments by anti-inflammatory activity in rats. Biomol Ther (Seoul) 2013;21:381-90. https://doi.org/10.4062/biomolther.2013.053
  69. Yoon S-J, Park J-Y, Choi S, Lee J-B, Jung H, Kim T-D, Yoon SR, Choi I, Shim S, Park Y-J. Ginsenoside Rg3 regulates S-nitrosylation of the NLRP3 inflammasome via suppression of iNOS. Biochem Biophys Res Commun 2015;463:1184-9. https://doi.org/10.1016/j.bbrc.2015.06.080
  70. Kim TW, Joh EH, Kim B, Kim DH. Ginsenoside Rg5 ameliorates lung inflammation in mice by inhibiting the binding of LPS to toll-like receptor-4 on macrophages. Int Immunopharmacol 2012;12:110-6. https://doi.org/10.1016/j.intimp.2011.10.023
  71. Lee SM. Anti-inflammatory effects of ginsenosides Rg5, Rz1, and Rk1: inhibition of $TNF-{\alpha}$-induced $NF-{\kappa}B$, COX-2, and iNOS transcriptional expression. Phytother Res 2014;28:1893-6. https://doi.org/10.1002/ptr.5203
  72. Chu S, Gu J, Feng L, Liu J, Zhang M, Jia X, Liu M, Yao D. Ginsenoside Rg5 improves cognitive dysfunction and beta-amyloid deposition in STZ-induced memory impaired rats via attenuating neuroinflammatory responses. Int Immunopharmacol 2014;19:317-26. https://doi.org/10.1016/j.intimp.2014.01.018
  73. Kim E-J, Jung I-H, Van Le TK, Jeong J-J, Kim N-J, Kim D-H. Ginsenosides Rg5 and Rh3 protect scopolamine-induced memory deficits in mice. J Ethnopharmacol 2013;146:294-9. https://doi.org/10.1016/j.jep.2012.12.047
  74. Ahn S, Siddiqi MH, Aceituno VC, Simu SY, Zhang J, Perez ZEJ, Kim Y-J, Yang D-C. Ginsenoside Rg5: Rk1 attenuates $TNF-{\alpha}/IFN-{\gamma}$-induced production of thymus-and activation-regulated chemokine (TARC/CCL17) and LPS-induced NO production via downregulation of $NF-{\kappa}B$/p38 MAPK/STAT1 signaling in human keratinocytes and macrophages. In Vitro Cell Dev Biol Anim 2015:1-9.
  75. Park E-K, Choo M-K, Han MJ, Kim D-H. Ginsenoside Rh1 possesses antiallergic and anti-inflammatory activities. Int Allergy Immunol 2004;133:113-20. https://doi.org/10.1159/000076383
  76. Jung J-S, Kim D-H, Kim H-S. Ginsenoside Rh1 suppresses inducible nitric oxide synthase gene expression in $IFN-{\gamma}$-stimulated microglia via modulation of JAK/STAT and ERK signaling pathways. Biochem Biophys Res Commun 2010;397:323-8. https://doi.org/10.1016/j.bbrc.2010.05.117
  77. Zheng H, Jeong Y, Song J, Ji GE. Oral administration of ginsenoside Rh1 inhibits the development of atopic dermatitis-like skin lesions induced by oxazolone in hairless mice. Int Immunopharmacol 2011;11:511-8. https://doi.org/10.1016/j.intimp.2010.12.022
  78. Bae E-A, Kim E-J, Park J-S, Kim H-S, Ryu JH, Kim D-H. Ginsenosides Rg3 and Rh2 inhibit the activation of AP-1 and protein kinase A pathway in lipopolysaccharide/interferon-gamma-stimulated BV-2 microglial cells. Planta Med 2006;72:627-33. https://doi.org/10.1055/s-2006-931563
  79. Choi K, Kim M, Ryu J, Choi C. Ginsenosides compound K and Rh 2 inhibit tumor necrosis $ factor-{\alpha}$-induced activation of the $NF-{\kappa}B$ and JNK pathways in human astroglial cells. Neurosci Lett 2007;421:37-41. https://doi.org/10.1016/j.neulet.2007.05.017
  80. Li LC, Piao HM, Zheng MY, Lin ZH, Choi YH, Yan GH. Ginsenoside Rh2 attenuates allergic airway inflammation by modulating nuclear $factor-{\kappa}B$ activation in a murine model of asthma. Mol Med Rep 2015;12:6946-54. https://doi.org/10.3892/mmr.2015.4272
  81. Bi W-Y, Fu B-D, Shen H-Q, Wei Q, Zhang C, Song Z, Qin Q-Q, Li H-P, Lv S, Wu S-C. Sulfated derivative of 20 (S)-ginsenoside Rh2 inhibits inflammatory cytokines through MAPKs and NF-kappa B pathways in LPS-induced RAW264.7 macrophages. Inflammation 2012;35:1659-68. https://doi.org/10.1007/s10753-012-9482-1
  82. Yi P-F, Bi W-Y, Shen H-Q, Wei Q, Zhang L-Y, Dong H-B, Bai H-L, Zhang C, Song Z, Qin Q-Q. Inhibitory effects of sulfated 20 (S)-ginsenoside Rh2 on the release of pro-inflammatory mediators in LPS-induced RAW 264.7 cells. Eur J Pharmacol 2013;712:60-6. https://doi.org/10.1016/j.ejphar.2013.04.036
  83. Kim BH, Lee YG, Park TY, Kim HB, Rhee MH, Cho JY. Ginsenoside Rp1, a ginsenoside derivative, blocks lipopolysaccharide-induced interleukin-1beta production via suppression of the NF-kappaB pathway. Planta Med 2009;75:321-6. https://doi.org/10.1055/s-0028-1112218
  84. Shen T, Lee J-H, Park M-H, Lee Y-G, Rho H-S, Kwak Y-S, Rhee M-H, Park Y-C, Cho J-Y. Ginsenoside Rp 1, a ginsenoside derivative, blocks promoter activation of iNOS and Cox-2 genes by suppression of an $IKK{\beta}$-mediated $NF-{\kappa}B$ pathway in HEK293 cells. J Ginseng Res 2011;35:200-8. https://doi.org/10.5142/jgr.2011.35.2.200