Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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The anti-platelet activity of panaxadiol fraction and panaxatriol fraction of Korean Red Ginseng in vitro and ex vivo

  • Yuan Yee Lee (College of Veterinary Medicine, Kyungpook National University) ;
  • Yein Oh (College of Veterinary Medicine, Kyungpook National University) ;
  • Min-Soo Seo (College of Veterinary Medicine, Kyungpook National University) ;
  • Min-Goo Seo (College of Veterinary Medicine, Kyungpook National University) ;
  • Jee Eun Han (College of Veterinary Medicine, Kyungpook National University) ;
  • Kyoo-Tae Kim (College of Veterinary Medicine, Kyungpook National University) ;
  • Jin-Kyu Park (College of Veterinary Medicine, Kyungpook National University) ;
  • Sung Dae Kim (College of Veterinary Medicine, Kyungpook National University) ;
  • Sang-Joon Park (College of Veterinary Medicine, Kyungpook National University) ;
  • Dongmi Kwak (College of Veterinary Medicine, Kyungpook National University) ;
  • Man Hee Rhee (College of Veterinary Medicine, Kyungpook National University)
  • Received : 2022.12.16
  • Accepted : 2023.03.26
  • Published : 2023.09.01
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Abstract

Background: The anti-platelet activity of the saponin fraction of Korean Red Ginseng has been widely studied. The saponin fraction consists of the panaxadiol fraction (PDF) and panaxatriol fraction (PTF); however, their anti-platelet activity is yet to be compared. Our study aimed to investigate the potency of anti-platelet activity of PDF and PTF and to elucidate how well they retain their anti-platelet activity via different administration routes. Methods: For ex vivo studies, Sprague-Dawley rats were orally administered 250 mg/kg PDF and PTF for 7 consecutive days before blood collection via cardiac puncture. Platelet aggregation was conducted after isolation of the washed platelets. For in vitro studies, washed platelets were obtained from Sprague-Dawley rats. Collagen and adenosine diphosphate (ADP) were used to induce platelet aggregation. Collagen was used as an agonist for assaying adenosine triphosphate release, thromboxane B2, serotonin, cyclic adenosine monophosphate, and cyclic guanosine monophosphate (cGMP) release. Results: When treated ex vivo, PDF not only inhibited ADP and collagen-induced platelet aggregation, but also upregulated cGMP levels and reduced platelet adhesion to fibronectin. Furthermore, it also inhibited Akt phosphorylation induced by collagen treatment. Panaxadiol fraction did not exert any antiplatelet activity in vitro, whereas PTF exhibited potent anti-platelet activity, inhibiting ADP, collagen, and thrombin-induced platelet aggregation, but significantly elevated levels of cGMP. Conclusion: Our study showed that in vitro and ex vivo PDF and PTF treatments exhibited different potency levels, indicating possible metabolic conversions of ginsenosides, which altered the content of ginsenosides capable of preventing platelet aggregation.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No.2022R1A2C1012963).

References

  1. Sang Y, Roest M, de Laat B, de Groot PG, Huskens D. Interplay between platelets and coagulation. Blood Rev 2021;46:100733.
  2. Estevez B, Du X. New concepts and mechanisms of platelet activation signaling. Physiology 2017;32(2):162-77. https://doi.org/10.1152/physiol.00020.2016
  3. Ruggeri Z. Von Willebrand factor, platelets and endothelial cell interactions. J Thromb Haemost 2003;1(7):1335-42. https://doi.org/10.1046/j.1538-7836.2003.00260.x
  4. Daub K, Seizer P, Stellos K, Kramer BF, Bigalke B, Schaller M, Fateh-Moghadam S, Gawaz S, Lindemann S. Oxidized LDL-activated platelets induce vascular inflammation. Semin Thromb Hemost 2010;36(2):145-56. https://doi.org/10.1055/s-0030-1251498
  5. Galgano L, Guidetti GF, Torti M, Canobbio I. The controversial role of LPS in platelet activation in vitro. Int J Mol Sci 2022;23(18):10900.
  6. Pircher J, Engelmann B, Massberg S, Schulz C. Platelet-neutrophil crosstalk in atherothrombosis. Thromb Haemost 2019;119(8):1274-82. https://doi.org/10.1055/s-0039-1692983
  7. Marquardt L, Ruf A, Mansmann U, Winter R, Schuler M, Buggle F, Mayer H, Grau AJ. Course of platelet activation markers after ischemic stroke. Stroke 2002;33(11):2570-4. https://doi.org/10.1161/01.STR.0000034398.34938.20
  8. Cui J, Li H, Chen Z, Dong T, He X, Wei Y, Li Z, Duan J, Cao T, Chen Q, et al. Thrombo-inflammation and immunological response in ischemic stroke: focusing on platelet-tregs interaction. Front Cell Neurosci 2022;16:955385.
  9. 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
  10. Hyun SH, Bhilare KD, G, Park C-K, Kim J-H. Effects of Panax ginseng and ginsenosides on oxidative stress and cardiovascular diseases: pharmacological and therapeutic roles. J Ginseng Res 2022;46(1):33-8. https://doi.org/10.1016/j.jgr.2021.07.007
  11. Yoon SJ, Kim SK, Lee NY, Choi YR, Kim HS, Gupta H, Youn GS, Sung H, Shin MJ, Suk KT. Effect of Korean red ginseng on metabolic syndrome. J Ginseng Res 2021;45(3):380-9. https://doi.org/10.1016/j.jgr.2020.11.002
  12. Ratan ZA, Youn SH, Kwak Y-S, Han C-K, Haidere MF, Kim JK, Min H, Jung Y-J, Hosseinzadeh H, Hyun SH. Adaptogenic effects of Panax ginseng on modulation of immune functions. J Ginseng Res 2021;45(1):32-40. https://doi.org/10.1016/j.jgr.2020.09.004
  13. 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
  14. Irfan M, Kim M, Rhee MH. Anti-platelet role of Korean ginseng and ginsenosides in cardiovascular diseases. J Ginseng Res 2020;44(1):24-32. https://doi.org/10.1016/j.jgr.2019.05.005
  15. Kim JH, Kang SA, Han SM, Shim I. Comparison of the antiobesity effects of the protopanaxadiol-and protopanaxatriol-type saponins of red ginseng. Phytother Res 2009;23(1):78-85. https://doi.org/10.1002/ptr.2561
  16. Won H-J, Kim HI, Park T, Kim H, Jo K, Jeon H, Ha SJ, Hyun JM, Jeong A, Kim JS, et al. Non-clinical pharmacokinetic behavior of ginsenosides. J Ginseng Res 2019;43(3):354-60. https://doi.org/10.1016/j.jgr.2018.06.001
  17. Sun J, Wu W, Guo Y, Qin Q, Liu S. Pharmacokinetic study of ginsenoside Rc and simultaneous determination of its metabolites in rats using RRLC-Q-TOF-MS. J Pharm Biomed Anal 2014;88:16-21. https://doi.org/10.1016/j.jpba.2013.08.015
  18. Bae E-A, Choo M-K, Park E-K, Park S-Y, Shin H-Y, Kim D-H. Metabolism of ginsenoside Rc by human intestinal bacteria and its related antiallergic activity. Biol Pharm Bull 2002;25(6):743e7.
  19. Akao T, Kida H, Kanaoka M, Hattori M, Kobashi K. Drug metabolism: intestinal bacterial hydrolysis is required for the appearance of compound K in rat plasma after oral administration of ginsenoside Rb1 from Panax ginseng. J Pharm Pharmacol 1998;50(10):1155-60. https://doi.org/10.1111/j.2042-7158.1998.tb03327.x
  20. Chen G, Yang M, Song Y, Lu Z, Zhang J, Huang H, Guan S, Wu L, Guo DA. Comparative analysis on microbial and rat metabolism of ginsenoside Rb1 by high-performance liquid chromatography coupled with tandem mass spectrometry. Biomed Chromatogr 2008;22(7):779-85. https://doi.org/10.1002/bmc.1001
  21. Jeong D, Irfan M, Kim S-D, Kim S, Oh J-H, Park C-K, Kim HK, Rhee MH. Ginsenoside Rg3-enriched red ginseng extract inhibits platelet activation and in vivo thrombus formation. J Ginseng Res 2017;41(4):548-55. https://doi.org/10.1016/j.jgr.2016.11.003
  22. Yang L, Deng Y, Xu S, Zeng X. In vivo pharmacokinetic and metabolism studies of ginsenoside Rd. J Chromatogr B Analyt Technol Biomed Life Sci 2007;854(1-2):77-84. https://doi.org/10.1016/j.jchromb.2007.04.014
  23. Wang Y, Liu T, Wang W, Wang B. Research on the transformation of ginsenoside Rg1 by intestinal flora. Zhongguo Zhong Yao Za Zhi 2001;26(3):188-90.
  24. Bae E-A, Shin J-e, Kim D-H. Metabolism of ginsenoside Re by human intestinal microflora and its estrogenic effect. Biol Pharm Bull 2005;28(10):1903-8. https://doi.org/10.1248/bpb.28.1903
  25. Zhou W, Chai H, Lin PH, Lumsden AB, Yao Q, Chen C. Ginsenoside Rb1 blocks homocysteine-induced endothelial dysfunction in porcine coronary arteries. J Vasc Surg 2005;41(5):861-8. https://doi.org/10.1016/j.jvs.2005.01.054
  26. Wang X, Zhang J. Effect of ginsenoside Rb1 on mouse sexual function and its mechanism. Acta Pharm Sin 2000;35(7):492-5.
  27. Kwon H-W. Inhibitory effect of 20 (S)-Ginsenoside Rg3 on human platelet aggregation and intracellular Ca2+ levels via cyclic adenosine monophosphate dependent manner. Prev Nutr Food Sci 2018;23(4):317-25. https://doi.org/10.3746/pnf.2018.23.4.317
  28. Gao Y, Zhu P, Xu S-F, Li Y-Q, Deng J, Yang D-L. Ginsenoside Re inhibits PDGF-BB-induced VSMC proliferation via the eNOS/NO/cGMP pathway. Biomed Pharmacother 2019;115:108934.
  29. Zhang H, Zhou Q, Li X, Zhao W, Wang Y, Liu H. Li N. Ginsenoside Re promotes human sperm capacitation through nitric oxide-dependent pathway. Mol Reprod Dev 2007;74(4):497-501. https://doi.org/10.1002/mrd.20583
  30. Catalkaya G, Venema K, Lucini L, Rocchetti G, Delmas D, Daglia M, De Filippis A, Xiao H, Quiles JL, Xiao j, et al. Interaction of dietary polyphenols and gut microbiota: microbial metabolism of polyphenols, influence on the gut microbiota, and implications on host health. Food Front 2020;1:109-33. https://doi.org/10.1002/fft2.25
  31. Rodrigues DB, Marques MC, Hacke A, Loubet Filho PS, Cazarin CBB, Mariutti LRB. Trust your gut: bioavailability and bioaccessibility of dietary compounds. Curr Res Food Sci 2022 Jan 11;5:228e33.
  32. Vissenaekens H, Grootaert C, Rajkovic A, De Schutter K, Raes K, Smagghe G, Van de Wiele T, Van Camp J. Cell line-dependent increase in cellular quercetin accumulation upon stress induced by valinomycin and lipopolysaccharide, but not by TNF-a. Food Res Int 2019;125:108596.
  33. Rojo-Poveda O, Barbosa-Pereira L, El Khattabi C, Youl EN, Bertolino M, Delporte C, Pochet S, Stevigny C. Polyphenolic and methylxanthine bio-accessibility of cocoa bean shell functional biscuits: metabolomics approach and intestinal permeability through caco-2 cell models. Antioxidants 2020;9(11):1164.