Journal of Ginseng Research

  • 제48권4호
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  • Pages.428-434
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  • 2024
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  • 1226-8453(pISSN)
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  • 2093-4947(eISSN)
고려인삼학회 (The Korean Society of Ginseng)
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Red ginseng extract inhibits lipopolysaccharide-induced platelet-leukocyte aggregates in mice

  • Yuan Yee Lee (Department of Veterinary Medicine, Kyungpook National University) ;
  • Sung Dae Kim (Department of Veterinary Medicine, Kyungpook National University) ;
  • Jin-Kyu Park (Department of Veterinary Medicine, Kyungpook National University) ;
  • Won-Jae Lee (Department of Veterinary Medicine, Kyungpook National University) ;
  • Jee Eun Han (Department of Veterinary Medicine, Kyungpook National University) ;
  • Min-Soo Seo (Department of Veterinary Medicine, Kyungpook National University) ;
  • Min-Goo Seo (Department of Veterinary Medicine, Kyungpook National University) ;
  • Seulgi Bae (Department of Veterinary Medicine, Kyungpook National University) ;
  • Dongmi Kwak (Department of Veterinary Medicine, Kyungpook National University) ;
  • Evelyn Saba (Department of Veterinary Biomedical Sciences, Faculty of Veterinary and Animal Sciences, Pir Mehr Ali Shah Arid Agriculture University) ;
  • Man Hee Rhee (Department of Veterinary Medicine, Kyungpook National University)
  • 투고 : 2023.11.22
  • 심사 : 2024.03.29
  • 발행 : 2024.07.01
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초록

Background: Platelet-leukocyte aggregates (PLAs) play important roles in cardiovascular disease and sepsis. Red ginseng extract (RGE) has been well-studied for its antiplatelet and anti-inflammatory activities. However, the potential inhibitory effects of RGE on PLA have not been investigated. Methods: Six-week-old ICR mice were given oral gavage of RGE for 7 days, followed by an intraperitoneal injection of 15 mg/kg of lipopolysaccharide. Mice were euthanized 24 h later, and blood samples were collected for further analysis. Flow cytometry was utilized to sort populations of PLAs and platelet-neutrophil aggregates (PNAs). By using confocal microscopy, PNAs were validated. Morphological changes in platelets and leukocytes were visualized with scanning electron microscopy. Expressions of tissue factor (TF) and platelet factor 4 (PF4) were investigated using enzyme-linked immunosorbent assay. Results: Populations of activated platelets, PLAs and PNAs, were significantly increased with LPS-induction. Treatment with 200 and 400 mg/kg of RGE decreased platelet activation. Moreover, the populations of PLAs and PNAs were reduced. PNAs were visible in the blood of septic mice, and this was attenuated by treatment with 400 mg/kg of RGE. Morphologically, sepsisinduced platelet activation and fibrin formation in the blood. This was reduced with RGE treatment. Sepsis-induced increase in the plasma levels of TF and PF4 was also reduced with RGE treatment. Conclusion: This study shows that RGE is a potential therapeutic that reduces the activation of platelets and targets PLA and PNA formation. Detailed inhibitory mechanisms of RGE should be studied.

키워드

과제정보

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Ministry of Science and ICT, Republic of Korea (No. 2022R1A2C1012963).

참고문헌

  1. McGregor L, Martin J, McGregor JL. Platelet-leukocyte aggregates and derived microparticles in inflammation, vascular remodelling and thrombosis. Front Biosci 2006;11(1):830-7. https://doi.org/10.2741/1840
  2. Cerletti C, Tamburrelli C, Izzi B, Gianfagna F, De Gaetano G. Platelet-leukocyte interactions in thrombosis. Thromb Res 2012;129(3):263-6. https://doi.org/10.1016/j.thromres.2011.10.010
  3. Freedman JE, Loscalzo J. Platelet-monocyte aggregates: bridging thrombosis and inflammation. Circulation 2002;105(18):2130-2. https://doi.org/10.1161/01.CIR.0000017140.26466.F5
  4. Pircher J, Engelmann B, Massberg S, Schulz C. Platelet-neutrophil crosstalk in atherothrombosis. Thromb Haemostasis 2019;119(8):1274-82. https://doi.org/10.1055/s-0039-1692983
  5. Li N. Platelet-lymphocyte cross-talk. J Leukoc Biol 2008;83(5):1069-78. https://doi.org/10.1189/jlb.0907615
  6. Schrottmaier WC, Mussbacher M, Salzmann M, Assinger A. Platelet-leukocyte interplay during vascular disease. Atherosclerosis 2020;307:109-20. https://doi.org/10.1016/j.atherosclerosis.2020.04.018
  7. Rudiger A, Singer M. Mechanisms of sepsis-induced cardiac dysfunction. Crit Care Med 2007;35(6):1599-608. https://doi.org/10.1097/01.CCM.0000266683.64081.02
  8. de Stoppelaar SF, van't Veer C, van der Poll T. The role of platelets in sepsis. Thromb Haemostasis 2014;112(10):666-77. https://doi.org/10.1160/TH14-02-0126
  9. Gawaz M, Dickfeld T, Bogner C, Fateh-Moghadam S, Neumann F. Platelet function in septic multiple organ dysfunction syndrome. Intensive Care Med 1997;23(4):379-85. https://doi.org/10.1007/s001340050344
  10. Carestia A, Davis RP, Grosjean H, Lau MW, Jenne CN. Acetylsalicylic acid inhibits intravascular coagulation during Staphylococcus aureus-induced sepsis in mice. Blood 2020;135(15):1281-6. https://doi.org/10.1182/blood.2019002783
  11. Ma A, Kubes P. Platelets, neutrophils, and neutrophil extracellular traps (NETs) in sepsis. J Thromb Haemostasis 2008;6(3):415-20. https://doi.org/10.1111/j.1538-7836.2007.02865.x
  12. Sakurai K, Miyashita T, Okazaki M, Yamaguchi T, Ohbatake Y, Nakanuma S, et al. Role for neutrophil extracellular traps (NETs) and platelet aggregation in early sepsis-induced hepatic dysfunction. In Vivo 2017;31(6):1051-8.
  13. Rondina MT, Carlisle M, Fraughton T, Brown SM, Miller IIIRR, Harris ES, et al. Platelet-monocyte aggregate formation and mortality risk in older patients with severe sepsis and septic shock. J Gerontol A Biol Sci Med 2015;70(2):225-31. https://doi.org/10.1093/gerona/glu082
  14. Gawaz M, Fateh-Moghadam S, Pilz G, Gurland HJ, Werdan K. Platelet activation and interaction with leucocytes in patients with sepsis or multiple organ failure. Eur J Clin Invest 1995;25(11):843-51. https://doi.org/10.1111/j.1365-2362.1995.tb01694.x
  15. Min J-H, Cho H-J, Yi Y-S. A novel mechanism of Korean Red Ginseng-mediated anti-inflammatory action via targeting caspase-11 non-canonical inflammasome in macrophages. J Ginseng Res 2022;46(5):675-82. https://doi.org/10.1016/j.jgr.2021.12.009
  16. Lee J-O, Yang Y, Tao Y, Yi Y-S, Cho JY. Korean Red Ginseng saponin fraction exerts anti-inflammatory effects by targeting the NF-κB and AP-1 pathways. J Ginseng Res 2022;46(3):489-95. https://doi.org/10.1016/j.jgr.2022.02.004
  17. Irfan M, Lee YY, Lee K-J, Kim SD, Rhee MH. Comparative antiplatelet and antithrombotic effects of red ginseng and fermented red ginseng extracts. J Ginseng Res 2022;46(3):387-95. https://doi.org/10.1016/j.jgr.2021.05.010
  18. Lee YY, Kim SD, Park S-C, Rhee MH. Panax ginseng: inflammation, platelet aggregation, thrombus formation, and atherosclerosis crosstalk. J Ginseng Res 2022;46(1):54-61. https://doi.org/10.1016/j.jgr.2021.09.003
  19. Seong HR, Wang C, Irfan M, Kim YE, Jung G, Park SK, et al. DK-MGAR101, an extract of adventitious roots of mountain ginseng, improves blood circulation by inhibiting endothelial cell injury, platelet aggregation, and thrombus formation. J Ginseng Res 2022;46(5):683-9. https://doi.org/10.1016/j.jgr.2022.01.001
  20. Vardon-Bounes F, Garcia C, Piton A, Series J, Gratacap M-P, Poette M, et al. Evolution of platelet activation parameters during septic shock in intensive care unit. Platelets 2022;33(6):918-25. https://doi.org/10.1080/09537104.2021.2007873
  21. Shannon O. The role of platelets in sepsis. Res Pract Thromb Haemost 2021;5(1):27-37. https://doi.org/10.1002/rth2.12465
  22. Sygitowicz G, Sitkiewicz D. Molecular mechanisms of organ damage in sepsis: an overview. Braz J Infect Dis 2021;24:552-60. https://doi.org/10.1016/j.bjid.2020.09.004
  23. Finsterbusch M, Schrottmaier WC, Kral-Pointner JB, Salzmann M, Assinger A. Measuring and interpreting platelet-leukocyte aggregates. Platelets 2018;29(7):677-85. https://doi.org/10.1080/09537104.2018.1430358
  24. Chirinos JA, Heresi GA, Velasquez H, Jy W, Jimenez JJ, Ahn E, et al. Elevation of endothelial microparticles, platelets, and leukocyte activation in patients with venous thromboembolism. J Am Coll Cardiol 2005;45(9):1467-71. https://doi.org/10.1016/j.jacc.2004.12.075
  25. Hasanpour M, Maleki S, Rezaee H, Aminzadeh B, Abbasi Shaye Z, Keykhosravi E. Glycoprotein IIb/IIIa inhibitors in the treatment of thromboembolic events related to endovascular treatment of cerebral aneurysms-systematic review and metaanalysis. NeuroRadiol J 2023:19714009231166090.
  26. Pluta K, Porebska K, Urbanowicz T, Gasecka A, Olasinska-Wisniewska A, Targonski R, et al. Platelet-leucocyte aggregates as novel biomarkers in cardiovascular diseases. Biology 2022;11(2):224.
  27. Fullard JF. The role of the platelet glycoprotein IIb/IIIa in thrombosis and haemostasis. Curr Pharmaceut Des 2004;10(14):1567-76. https://doi.org/10.2174/1381612043384682
  28. Merten M, Thiagarajan P. P-selectin expression on platelets determines size and stability of platelet aggregates. Circulation 2000;102(16):1931-6. https://doi.org/10.1161/01.CIR.102.16.1931
  29. Jin YR, Yu JY, Lee JJ, You SH, Chung JH, Noh JY, et al. Antithrombotic and antiplatelet activities of Korean red ginseng extract. Basic Clin Pharmacol Toxicol 2007;100(3):170-5. https://doi.org/10.1111/j.1742-7843.2006.00033.x
  30. Jeon BR, Kim SJ, Hong SB, Park H-J, Cho JY, Rhee MH. The inhibitory mechanism of crude saponin fraction from Korean Red Ginseng in collagen-induced platelet aggregation. J Ginseng Res 2015;39(3):279-85. https://doi.org/10.1016/j.jgr.2015.02.001
  31. Lee D-H, Cho H-J, Kim H-H, Rhee MH, Ryu J-H, Park H-J. Inhibitory effects of total saponin from Korean red ginseng via vasodilator-stimulated phosphoproteinSer157 phosphorylation on thrombin-induced platelet aggregation. J Ginseng Res 2013;37(2):176-86. https://doi.org/10.5142/jgr.2013.37.176
  32. Youn SH, Lee SM, Han C-K, In G, Park C-K, Hyun SH. Immune activity of polysaccharide fractions isolated from Korean red ginseng. Molecules 2020;25(16):3569.
  33. Cox D, Kerrigan SW, Watson SP. Platelets and the innate immune system: mechanisms of bacterial-induced platelet activation. J Thromb Haemostasis 2011;9(6):1097-107. https://doi.org/10.1111/j.1538-7836.2011.04264.x
  34. Hottz ED, Azevedo-Quintanilha IG, Palhinha L, Teixeira L, Barreto EA, Pao CR, et al. Platelet activation and platelet-monocyte aggregate formation trigger tissue factor expression in patients with severe COVID-19. Blood 2020;136(11):1330-41. https://doi.org/10.1182/blood.2020007252
  35. Saba E, Jeong D, Irfan M, Lee YY, Park S-J, Park C-K, et al. Anti-inflammatory activity of Rg3-enriched Korean red ginseng extract in murine model of sepsis. Evid Based Complement Alternat Med 2018:6874692.
  36. Yu T, Tang Y, Zhang F, Zhang L. Roles of ginsenosides in sepsis. J Ginseng Res 2023;47(1):1-8. https://doi.org/10.1016/j.jgr.2022.05.004