Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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A brief method for preparation of gintonin-enriched fraction from ginseng

  • Choi, Sun-Hye (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University) ;
  • Jung, Seok-Won (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University) ;
  • Kim, Hyun-Sook (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University) ;
  • Kim, Hyeon-Joong (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University) ;
  • Lee, Byung-Hwan (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University) ;
  • Kim, Joon Yong (VMTH, Konkuk University) ;
  • Kim, Jung-Hyun (VMTH, Konkuk University) ;
  • Hwang, Sung Hee (Department of Pharmaceutical Engineering, Sangji University) ;
  • Rhim, Hyewon (Life Science Division, Korea Institute of Science and Technology) ;
  • Kim, Hyoung-Chun (Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University) ;
  • Nah, Seung-Yeol (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University)
  • Received : 2015.02.25
  • Accepted : 2015.05.10
  • Published : 2015.10.15
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Abstract

Background: Ginseng has been used as a tonic for invigoration of the human body. In a previous report, we identified a novel candidate responsible for the tonic role of ginseng, designated gintonin. Gintonin induces $[Ca^{2+}]_i$ transient in animal cells via lysophosphatidic acid receptor activation. Gintonin-mediated $[Ca^{2+}]_i$ transient is linked to anti-Alzheimer's activity in transgenic Alzheimer's disease animal model. The previous method for gintonin preparation included multiple steps. The aim of this study is to develop a simple method of gintonin fraction with a high yield. Methods: We developed a brief method to obtain gintonin using ethanol and water. We extracted ginseng with fermentation ethanol and fractionated the extract with water to obtain water-soluble and water-insoluble fractions. The water-insoluble precipitate, rather than the water-soluble supernatant, induced a large $[Ca^{2+}]_i$ transient in primary astrocytes. We designated this fraction as gintonin-enriched fraction (GEF). Results: The yield of GEF was approximately 6-fold higher than that obtained in the previous gintonin preparation method. The apparent molecular weight of GEF, determined using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, was equivalent to that obtained in the previous gintonin preparation method. GEF induced $[Ca^{2+}]_i$ transient in cortical astrocytes. The effective dose (ED50) was $0.3{\pm}0.09{\mu}g/mL$. GEF used the same signal transduction pathway as gintonin during $[Ca^{2+}]_i$ transient induction in mouse cortical astrocytes. Conclusion: Because GEF can be prepared through water precipitation of ginseng ethanol extract and is easily reproducible with high yield, it could be commercially utilized for the development of gintoninderived functional health food and natural medicine.

Keywords

References

  1. Im DS, Nah SY. Yin and Yang of ginseng pharmacology: ginsenosides vs gintonin. Acta Pharmacol Sin 2013;34:1367-73. https://doi.org/10.1038/aps.2013.100
  2. Nah SY. Gintonin: a novel ginseng-derived ligand that targets G proteincoupled lysophosphatidic acid receptors. Curr Drug Targets 2012;13:1659-64. https://doi.org/10.2174/138945012803529947
  3. Choi SH, Lee BH, Kim HJ, Jung SW, Kim HS, Shin HC, Lee JH, Kim HC, Rhim H, Hwang SH, et al. Ginseng gintonin activates the human cardiac delayed rectifier $K^+$ channel: involvement of $Ca^{2+}$/calmodulin binding sites. Mol Cells 2014;37:656-63. https://doi.org/10.14348/molcells.2014.0087
  4. Lee JH, Choi SH, Lee BH, Hwang SH, Kim HJ, Rhee J, Chung C, Nah SY. Activation of lysophosphatidic acid receptor by gintonin inhibits Kv1.2 channel activity: involvement of tyrosine kinase and receptor protein tyrosine phosphatase ${\alpha}$. Neurosci Lett 2013;548:143-8. https://doi.org/10.1016/j.neulet.2013.05.048
  5. Choi SH, Lee BH, Hwang SH, Kim HJ, Lee SM, Kim HC, Rhim H, Nah SY. Molecular mechanisms of large-conductance $Ca^{2+}$-activated potassium channel activation by ginseng gintonin. Evid Based Complement Alternat Med 2013;2013:323709.
  6. Shin TJ, Kim HJ, Kwon BJ, Choi SH, Kim HB, Hwang SH, Lee BH, Lee SM, Zukin RS, Park JH, et al. Gintonin, a ginseng-derived novel ingredient, evokes long-term potentiation through N-methyl-D-aspartic acid receptor activation: involvement of LPA receptors. Mol Cells 2012;34:563-72. https://doi.org/10.1007/s10059-012-0254-4
  7. Choi SH, Kim HJ, Kim BR, Shin TJ, Hwang SH, Lee BH, Lee SM, Rhim H, Nah SY. Gintonin, a ginseng-derived lysophosphatidic acid receptor ligand, potentiates ATP-gated $P2X_1$ receptor channel currents. Mol Cells 2013;35:142-50. https://doi.org/10.1007/s10059-013-2293-x
  8. Kim BJ, Nam JH, Kim KH, Joo M, Ha TS, Weon KY, Choi S, Jun JY, Park EJ, Wie J, et al. Characteristics of gintonin-mediated membrane depolarization of pacemaker activity in cultured interstitial cells of Cajal. Cell Physiol Biochem 2014;34:873-90. https://doi.org/10.1159/000366306
  9. Park H, Kim S, Rhee J, Kim HJ, Han JS, Nah SY, Chung C. Synaptic enhancement induced by gintonin via lysophosphatidic acid receptor activation in fully developed central synapses. J Neurophysiol 2015;113:1493-500. https://doi.org/10.1152/jn.00667.2014
  10. Hwang SH, Shin EJ, Shin TJ, Lee BH, Choi SH, Kang J, Kim HJ, Kwon SH, Jang CG, Lee JH, et al. Gintonin, a ginseng-derived lysophosphatidic acid receptor ligand, attenuates Alzheimer's disease-related neuropathies: involvement of non-amyloidogenic processing. J Alzheimers Dis 2012;31:207-23. https://doi.org/10.3233/JAD-2012-120439
  11. Hwang SH, Lee BH, Kim HJ, Cho HJ, Shin HC, Im KS, Choi SH, Shin TJ, Lee SM, Nam SW, et al. Suppression of metastasis of intravenously-inoculated B16/F10 melanoma cells by the novel ginseng-derived ingredient, gintonin: involvement of autotaxin inhibition. Int J Oncol 2013;42:317-26. https://doi.org/10.3892/ijo.2012.1709
  12. Pyo MK, Choi SH, Hwang SH, Shin TJ, Lee BH, Lee SM, Lim YH, Kim DH, Nah SY. Novel glycolipoproteins from ginseng. J Ginseng Res 2011;35:92-103. https://doi.org/10.5142/jgr.2011.35.1.092
  13. Choi SH, Shin TJ, Lee BH, Hwang SH, Kang J, Kim HJ, Park CW, Nah SY. An edible gintonin preparation from ginseng. J Ginseng Res 2011;35:471-8. https://doi.org/10.5142/jgr.2011.35.4.471
  14. Shano S, Moriyama R, Chun J, Fukushima N. Lysophosphatidic acid stimulates astrocyte proliferation through LPA1. Neurochem Int 2008;52:216-20. https://doi.org/10.1016/j.neuint.2007.07.004
  15. Folch J, Lees M, Sloane-Stanely GH. A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 1957;226:497-509.
  16. Hwang SH, Shin TJ, Choi SH, Cho HJ, Lee BH, Pyo MK, Lee JH, Kang J, Kim HJ, Park CW, et al. Gintonin, newly identified compounds from ginseng, is novel lysophosphatidic acids-protein complexes and activates G protein-coupled lysophosphatidic acid receptors with high affinity. Mol Cells 2012;33:151-62. https://doi.org/10.1007/s10059-012-2216-z

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