Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Potential application of ginseng in sepsis: Applications of ginseng in sepsis

  • Fuxun Yang (Department of ICU, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China) ;
  • Jiajia Li (Department of ICU, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China) ;
  • Yunping Lan (Department of ICU, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China) ;
  • Yu Lei (Department of ICU, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China) ;
  • Fan Zeng (Department of ICU, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China) ;
  • Xiaobo Huang (Department of ICU, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China) ;
  • Xiaoxiu Luo (Department of ICU, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China) ;
  • Rongan Liu (Department of ICU, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China)
  • Received : 2022.03.15
  • Accepted : 2022.05.02
  • Published : 2023.05.01
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Abstract

Sepsis and septic shock affect millions of people worldwide each year with high clinical mortality rates. At present, basic research on sepsis has emerged in an endless stream, but there are few effective clinical translation results. Ginseng, a medicinal and edible representative of Araliaceae plants, contains a variety of biologically active compounds including ginsenosides, alkaloids, glycosides, polysaccharides, and polypeptides. Neuromodulation, anticancer activity, blood lipid regulation, and antithrombotic activity have been linked to ginseng treatment. At present, basic and clinical research have suggested various applications of ginseng in sepsis. In view of the different effects of various ginseng components on the pathogenesis of sepsis, and in order to further understand and develop the possible value of ginseng in sepsis, this manuscript reviews the application of various components of ginseng in the treatment of sepsis in recent years.

Keywords

References

  1. Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, Machado FR, McIntyre L, Ostermann M, Prescott HC, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med 2021;47(11):1181-247. https://doi.org/10.1007/s00134-021-06506-y
  2. Gentile LF, Moldawer LL. HMGB1 as a therapeutic target for sepsis: it's all in the timing! Expert Opin Ther Targets 2014;18(3):243-5. https://doi.org/10.1517/14728222.2014.883380
  3. Deutschman CS, Hellman J. Ferrer roca R, de backer D, coopersmith CM: the surviving sepsis campaign: basic/translational science research priorities. Crit Care Med 2020;48(8):1217-32. https://doi.org/10.1097/CCM.0000000000004408
  4. Ru W, Wang D, Xu Y, He X, Sun YE, Qian L, Zhou X, Qin Y. Chemical constituents and bioactivities of Panax ginseng (C. A. Mey.). Drug Discov Ther 2015;9(1):23-32. https://doi.org/10.5582/ddt.2015.01004
  5. van der Poll T, van de Veerdonk FL, Scicluna BP, Netea MG. The immunopathology of sepsis and potential therapeutic targets. Nat Rev Immunol 2017;17(7):407-20. https://doi.org/10.1038/nri.2017.36
  6. Xu HL, Chen GH, Wu YT, Xie LP, Tan ZB, Liu B, Fan HJ, Chen HM, Huang GQ, Liu M, et al. Ginsenoside Ro, an oleanolic saponin of Panax ginseng, exerts anti-inflammatory effect by direct inhibiting toll like receptor 4 signaling pathway. J Ginseng Res 2022;46(1):156-66. https://doi.org/10.1016/j.jgr.2021.05.011
  7. Kim MK, Kang H, Baek CW, Jung YH, Woo YC, Choi GJ, Shin HY, Kim KS. Antinociceptive and anti-inflammatory effects of ginsenoside Rf in a rat model of incisional pain. J Ginseng Res 2018;42(2):183-91. https://doi.org/10.1016/j.jgr.2017.02.005
  8. Yoon SJ, Park JY, Choi S, Lee JB, Jung H, Kim TD, Yoon SR, Choi I, Shim S, Park YJ. Ginsenoside Rg3 regulates S-nitrosylation of the NLRP3 inflammasome via suppression of iNOS. Biochem Biophys Res Commun 2015;463(4):1184-9. https://doi.org/10.1016/j.bbrc.2015.06.080
  9. Shi Y, Wang H, Zheng M, Xu W, Yang Y, Shi F. Ginsenoside Rg3 suppresses the NLRP3 inflammasome activation through inhibition of its assembly. Faseb J 2020;34(1):208-21. https://doi.org/10.1096/fj.201901537R
  10. Yayeh T, Jung KH, Jeong HY, Park JH, Song YB, Kwak YS, Kang HS, Cho JY, Oh JW, Kim SK, et al. Korean red ginseng saponin fraction downregulates proinflammatory mediators in LPS stimulated RAW264.7 cells and protects mice against endotoxic shock. J Ginseng Res 2012;36(3):263-9. https://doi.org/10.5142/jgr.2012.36.3.263
  11. Yang CS, Ko SR, Cho BG, Shin DM, Yuk JM, Li S, Kim JM, Evans RM, Jung JS, Song DK, et al. The ginsenoside metabolite compound K, a novel agonist of glucocorticoid receptor, induces tolerance to endotoxin-induced lethal shock. J Cell Mol Med 2008;12(5a):1739-53. https://doi.org/10.1111/j.1582-4934.2007.00181.x
  12. Wu LL, Jia BH, Sun J, Chen JX, Liu ZY, Liu Y. Protective effects of ginsenoside Rb1 on septic rats and its mechanism. Biomed Environ Sci 2014;27(4):300-3.
  13. Hur J, Lee HG, Kim E, Won JP, Cho Y, Choi MJ, Lee H, Seo HG. Ginseng leaf extract ameliorates the survival of endotoxemic mice by inhibiting the release of high mobility group box 1. J Food Biochem 2021;45(7):e13805.
  14. Kim JE, Lee W, Yang S, Cho SH, Baek MC, Song GY, Bae JS. Suppressive effects of rare ginsenosides, Rk1 and Rg5, on HMGB1-mediated septic responses. Food Chem Toxicol 2019;124:45-53. https://doi.org/10.1016/j.fct.2018.11.057
  15. Huynh DTN, Baek N, Sim S, Myung CS, Heo KS. Minor ginsenoside Rg2 and Rh1 attenuates LPS-induced acute liver and kidney damages via downregulating activation of TLR4-STAT1 and inflammatory cytokine production in macrophages. Int J Mol Sci 2020;21(18).
  16. Su F, Xue Y, Wang Y, Zhang L, Chen W, Hu S. Protective effect of ginsenosides Rg1 and Re on lipopolysaccharide-induced sepsis by competitive binding to Toll-like receptor 4. Antimicrob Agents Chemother 2015;59(9):5654-63. https://doi.org/10.1128/AAC.01381-15
  17. Lim J-K, Kang H-J, Kang S-N, Lee B-Y. Antioxidant and antimicrobial activities of various solvent fractions of fine ginseng root. Food Sci Biotechnol 2009;18(2):513-8.
  18. Xu L-L, Han T, Wu J-Z, Zhang Q-Y, Zhang H, Huang B-K, Rahman K, Qin L-P. Comparative research of chemical constituents, antifungal and antitumor properties of ether extracts of Panax ginseng and its endophytic fungus. Phytomedicine 2009;16(6e7):609-16. https://doi.org/10.1016/j.phymed.2009.03.014
  19. Ahn JY, Song JY, Yun YS, Jeong G, Choi IS. Protection of Staphylococcus aureus-infected septic mice by suppression of early acute inflammation and enhanced antimicrobial activity by ginsan. FEMS Immunol Med Microbiol 2006;46(2):187-97. https://doi.org/10.1111/j.1574-695X.2005.00021.x
  20. Lim DS, Bae KG, Jung IS, Kim CH, Yun YS, Song JY. Anti-septicaemic effect of polysaccharide from Panax ginseng by macrophage activation. J Infect 2002;45(1):32-8. https://doi.org/10.1053/jinf.2002.1007
  21. Nguyen CT, Luong TT, Lee SY, Kim GL, Kwon H, Lee HG, Park CK, Rhee DK. Panax ginseng aqueous extract prevents pneumococcal sepsis in vivo by potentiating cell survival and diminishing inflammation. Phytomedicine 2015;22(11):1055-61. https://doi.org/10.1016/j.phymed.2015.07.005
  22. Venet F, Monneret G. Advances in the understanding and treatment of sepsis-induced immunosuppression. Nat Rev Nephrol 2018;14(2):121-37. https://doi.org/10.1038/nrneph.2017.165
  23. Gupta DL, Bhoi S, Mohan T, Galwnkar S, Rao DN. Coexistence of Th1/Th2 and Th17/Treg imbalances in patients with post traumatic sepsis. Cytokine 2016;88:214-21. https://doi.org/10.1016/j.cyto.2016.09.010
  24. Bae J, Koo J, Kim S, Park TY, Kim MY. Ginsenoside Rp1 exerts anti-inflammatory effects via activation of dendritic cells and regulatory T. Cells. J Ginseng Res 2012;36(4):375-82. https://doi.org/10.5142/jgr.2012.36.4.375
  25. Zou Y, Tao T, Tian Y, Zhu J, Cao L, Deng X, Li J. Ginsenoside Rg1 improves survival in a murine model of polymicrobial sepsis by suppressing the inflammatory response and apoptosis of lymphocytes. J Surg Res 2013;183(2):760-6. https://doi.org/10.1016/j.jss.2013.01.068
  26. Ehrman RR, Sullivan AN, Favot MJ, Sherwin RL, Reynolds CA, Abidov A, Levy PD. Pathophysiology, echocardiographic evaluation, biomarker findings, and prognostic implications of septic cardiomyopathy: a review of the literature. Crit Care 2018;22(1):112.
  27. L'Heureux M, Sternberg M, Brath L, Turlington J, Kashiouris MG. Sepsis-induced cardiomyopathy: a comprehensive review. Curr Cardiol Rep 2020;22(5):35.
  28. Wu Y, Qin C, Lu X, Marchiori J, Feng Q. North American ginseng inhibits myocardial NOX2-ERK1/2 signaling and tumor necrosis factor-a expression in endotoxemia. Pharmacol Res 2016;111:217-25. https://doi.org/10.1016/j.phrs.2016.06.010
  29. Luo M, Yan D, Sun Q, Tao J, Xu L, Sun H, Zhao H. Ginsenoside Rg1 attenuates cardiomyocyte apoptosis and inflammation via the TLR4/NF-kB/NLRP3 pathway. J Cell Biochem 2020;121(4):2994-3004. https://doi.org/10.1002/jcb.29556
  30. Lopez R, Rello J, Taccone FS, Salem OBH, Bauer PR, Seguin A, van de Louw A, Metaxa V, Klouche K, Martin Loeches I, et al. Aminoglycosides in immunocompromised critically ill patients with bacterial pneumonia and septic shock: a post-hoc analysis of a prospective multicenter multinational cohort. Shock 2020;54(6):731-7. https://doi.org/10.1097/SHK.0000000000001553
  31. Liu Z, Pan H, Zhang Y, Zheng Z, Xiao W, Hong X, Chen F, Peng X, Pei Y, Rong J, et al. Ginsenoside-Rg1 attenuates sepsis-induced cardiac dysfunction by modulating mitochondrial damage via the P2X7 receptor-mediated Akt/GSK-3β signaling pathway. J Biochem Mol Toxicol 2022;36(1):e22885.
  32. Chen RC, Wang J, Yang L, Sun GB, Sun XB. Protective effects of ginsenoside Re on lipopolysaccharide-induced cardiac dysfunction in mice. Food Funct 2016;7(5):2278-87. https://doi.org/10.1039/C5FO01357G
  33. Yao YM, Zhang H. Better therapy for combat injury. Mil Med Res 2019;6(1):23.
  34. Hwang JW, Yao H, Caito S, Sundar IK, Rahman I. Redox regulation of SIRT1 in inflammation and cellular senescence. Free Radic Biol Med 2013;61:95-110. https://doi.org/10.1016/j.freeradbiomed.2013.03.015
  35. Xie J, Zhang X, Zhang L. Negative regulation of inflammation by SIRT1. Pharmacol Res 2013;67(1):60-7. https://doi.org/10.1016/j.phrs.2012.10.010
  36. Wang QL, Yang L, Peng Y, Gao M, Yang MS, Xing W, Xiao XZ. Ginsenoside Rg1 regulates SIRT1 to ameliorate sepsis-induced lung inflammation and injury via inhibiting endoplasmic reticulum stress and inflammation. Mediat Inflamm 2019;2019:6453296.
  37. Yuan Q, Jiang YW, Ma TT, Fang QH, Pan L. Attenuating effect of Ginsenoside Rb1 on LPS-induced lung injury in rats. J Inflamm 2014;11(1):40.
  38. Dal-Secco D, Freitas A, Abreu MA, Garlet TP, Rossi MA, Ferreira SH, Silva JS, Alves-Filho JC, Cunha FQ. Reduction of ICAM-1 expression by carbon monoxide via soluble guanylate cyclase activation accounts for modulation of neutrophil migration. Naunyn-Schmiedeberg's Arch Pharmacol 2010;381(6):483-93. https://doi.org/10.1007/s00210-010-0500-2
  39. Poston JT, Koyner JL. Sepsis associated acute kidney injury. BMJ 2019;364:k4891.
  40. Chen Y, Du Y, Li Y, Wang X, Gao P, Yang G, Fang Y, Meng Y, Zhao X, Saponin Panaxadiol, Improve Dexamethasone. Renal function in lipopolysaccharide-induced mouse model of acute kidney injury. PLoS One 2015;(7):10. e0134653. https://doi.org/10.e0134653
  41. Gao H, Kang N, Hu C, Zhang Z, Xu Q, Liu Y, Yang S. Ginsenoside Rb1 exerts anti-inflammatory effects in vitro and in vivo by modulating toll-like receptor 4 dimerization and NF-kB/MAPKs signaling pathways. Phytomedicine 2020;69:153197.
  42. Wu T, Wang L, An J, Wu CY, Wang Y, Qian L, Zhou J, Zhang YL, Zhou QQ, Wang XH, et al. Noninvasive imaging of stored red blood cell-transfusion aggravating sepsis-induced liver injury associated with increased activation of M1-polarized kupffer cells. Shock 2017;48(4):459-66. https://doi.org/10.1097/SHK.0000000000000867
  43. Bakalli I. Liver dysfunction in severe sepsis from respiratory syncytial virus. J Pediatr Intensive Care 2018;7(2):110-4. https://doi.org/10.1055/s-0037-1612609
  44. Feng H, Chen J, Wang H, Cheng Y, Zou Z, Zhong Q, Xu J. Roflumilast reverses polymicrobial sepsis-induced liver damage by inhibiting inflammation in mice. Lab Invest 2017;97(9):1008-19. https://doi.org/10.1038/labinvest.2017.59
  45. Crager S. Critically ill patients with end-stage liver disease. Emerg Med Clin 2019;37(3):511-27. https://doi.org/10.1016/j.emc.2019.03.008
  46. Kurland S, Furebring M, Lowdin E, Eliasson E, Nielsen EI, Sjolin J. Pharmaco-kinetics of caspofungin in critically ill patients in relation to liver dysfunction: differential impact of plasma albumin and bilirubin levels. Antimicrob Agents Chemother 2019;(6):63.
  47. Dai YW, Zhang CC, Zhao HX, Wan JZ, Deng LL, Zhou ZY, Dun YY, Liu CQ, Yuan D, Wang T. Chikusetsusaponin V attenuates lipopolysaccharide-induced liver injury in mice. Immunopharmacol Immunotoxicol 2016;38(3):167-74. https://doi.org/10.3109/08923973.2016.1153109
  48. Nguyen TLL, Huynh DTN, Jin Y, Jeon H, Heo KS. Protective effects of ginsenoside-Rg2 and -Rh1 on liver function through inhibiting TAK1 and STAT3-mediated inflammatory activity and Nrf2/ARE-mediated antioxidant signaling pathway. Arch Pharm Res (Seoul) 2021;44(2):241-52. https://doi.org/10.1007/s12272-020-01304-4
  49. Xing W, Yang L, Peng Y, Wang Q, Gao M, Yang M, Xiao X. Ginsenoside Rg3 attenuates sepsis-induced injury and mitochondrial dysfunction in liver via AMPK-mediated autophagy flux. Biosci Rep 2017;(4):37.
  50. Stubbs DJ, Yamamoto AK, Menon DK. Imaging in sepsis-associated encephalopathy-insights and opportunities. Nat Rev Neurol 2013;9(10):551-61. https://doi.org/10.1038/nrneurol.2013.177
  51. Kafa IM, Bakirci S, Uysal M, Kurt MA. Alterations in the brain electrical activity in a rat model of sepsis-associated encephalopathy. Brain Res 2010;1354:217-26. https://doi.org/10.1016/j.brainres.2010.07.049
  52. Li Y, Wang F, Luo Y. Ginsenoside Rg1 protects against sepsis-associated encephalopathy through beclin 1-independent autophagy in mice. J Surg Res 2017;207:181-9. https://doi.org/10.1016/j.jss.2016.08.080
  53. Mei X, Feng H, Shao B. Alleviation of sepsis-associated encephalopathy by ginsenoside via inhibition of oxidative stress and cell apoptosis: an experimental study. Pak J Pharm Sci 2020;33(6):2567-77.
  54. Kang A, Xie T, Zhu D, Shan J, Di L, Zheng X. Suppressive effect of ginsenoside Rg3 against lipopolysaccharide-induced depression-like behavior and neuroinflammation in mice. J Agric Food Chem 2017;65(32):6861-9. https://doi.org/10.1021/acs.jafc.7b02386
  55. Ma S, Evans RG, Iguchi N, Tare M, Parkington HC, Bellomo R, May CN, Lankadeva YR. Sepsis-induced acute kidney injury: a disease of the microcirculation. Microcirculation 2019;26(2):e12483.
  56. Chen GY, Chen X, King S, Cavassani KA, Cheng J, Zheng X, Cao H, Yu H, Qu J, Fang D, et al. Amelioration of sepsis by inhibiting sialidase-mediated disruption of the CD24-SiglecG interaction. Nat Biotechnol 2011;29(5):428-35. https://doi.org/10.1038/nbt.1846
  57. Blikslager AT, Moeser AJ, Gookin JL, Jones SL, Odle J. Restoration of barrier function in injured intestinal mucosa. Physiol Rev 2007;87(2):545-64. https://doi.org/10.1152/physrev.00012.2006
  58. Mittal R, Coopersmith CM. Redefining the gut as the motor of critical illness. Trends Mol Med 2014;20(4):214-23. https://doi.org/10.1016/j.molmed.2013.08.004
  59. Adiliaghdam F, Cavallaro P, Mohad V, Almpani M, Kuhn F, Gharedaghi MH, Najibi M, Rahme LG, Hodin RA. Targeting the gut to prevent sepsis from a cutaneous burn. JCI Insight 2020;(19):5.
  60. Haussner F, Chakraborty S, Halbgebauer R, Huber-Lang M. Challenge to the intestinal mucosa during sepsis. Front Immunol 2019;10:891.
  61. Lee W, Cho SH, Kim JE, Lee C, Lee JH, Baek MC, Song GY, Bae JS. Suppressive effects of ginsenoside Rh1 on HMGB1-mediated septic responses. Am J Chin Med 2019;47(1):119e33.
  62. Zhang Y, Sun K, Liu YY, Zhang YP, Hu BH, Chang X, Yan L, Pan CS, Li Q, Fan JY, et al. Ginsenoside Rb1 ameliorates lipopolysaccharide-induced albumin leakage from rat mesenteric venules by intervening in both trans- and par-acellular pathway. Am J Physiol Gastrointest Liver Physiol 2014;306(4):G289-300. https://doi.org/10.1152/ajpgi.00168.2013
  63. Zhang N, Liu J, Qiu Z, Ye Y, Zhang J, Lou T. Shenfu injection for improving cellular immunity and clinical outcome in patients with sepsis or septic shock. Am J Emerg Med 2017;35(1):1-6. https://doi.org/10.1016/j.ajem.2016.09.008
  64. Li MQ, Pan CG, Wang XM, Mo X, Shi ZX, Xu JY, Xu YJ, Han GJ. Effect of the Shenfu injection combined with early goal-directed therapy on organ functions and outcomes of septic shock patients. Cell Biochem Biophys 2015;72(3):807-12. https://doi.org/10.1007/s12013-015-0537-4
  65. Li Y, Zhang X, Lin P, Qiu H, Wei J, Cao Y, Pan S, Walline J, Qian C, Shan Z, et al. Effects of Shenfu injection in the treatment of septic shock patients: a multicenter, controlled, randomized, open-label trial. Evid Base Compl Alternat Med 2016;2016:2565169.