Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
권호 표지
DOI QR코드

DOI QR Code

Novel Glycolipoproteins from Ginseng

  • Pyo, Mi-Kyung (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University) ;
  • Choi, Sun-Hye (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University) ;
  • Hwang, Sung-Hee (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University) ;
  • Shin, Tae-Joon (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) ;
  • Lee, Sang-Mok (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University) ;
  • Lim, Yoong-Ho (Department of Bioscience and Biotechnology, Konkuk University) ;
  • Kim, Dong-Hyun (College of Pharmacy, Kyung Hee University) ;
  • Nah, Seung-Yeol (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University)
  • Received : 2010.11.08
  • Accepted : 2010.12.09
  • Published : 2011.03.29
Download PDF
⟨ Previous Next ⟩

Abstract

Ginseng has been used as a general tonic agent to invigorate human body. In the present study, we isolated novel glycolipoproteins from ginseng that activate $Ca^{2+}$-activated $Cl^-$ channel (CaCC) in Xenopus oocytes and transiently increase intracellular free $Ca^{2+}$ concentration ($[Ca^{2+}]_i$) in mouse Ehrlich ascites tumor cells. We named the active ingredients as gintonin. Gintonin exists in at least six different forms. The native molecular weight of gintonin is about 67 kDa but its apparent molecular weight is about 13 kDa, indicating that gintonin might be a pentamer. Gintonin is rich in hydrophobic amino acids. Its main carbohydrates are glucose and glucosamine. Its lipid components are linoleic, palmitic, oleic, and stearic acids. Gintonin actions were blocked by U73122, a phospholipase C inhibitor, 2-aminoethxydiphenyl borate, an inositol 1,4,5-trisphosphate receptor antagonist, or bis (o-aminophenoxy) ethane-N,N,N0,N0-tetracetic acid acetoxymethyl ester, a membrane permeable $Ca^{2+}$ chelator. In the present study, we for the first time isolated novel gintonin and showed the signaling pathways on gintonin-mediated CaCC activations and transient increase of $[Ca^{2+}]_i$. Since $[Ca^{2+}]_i$ as a second messenger plays a pivotal role in the regulation of diverse $Ca^{2+}$-dependent intracellular signal pathways, gintonin-mediated regulations of $[Ca^{2+}]_i$ might contribute to biological actions of ginseng.

Keywords

References

  1. Nah SY. Ginseng: recent advances and trends. Korean J Ginseng Sci 1997;21:1-12.
  2. Shibata S, Tanaka O, Soma K, Ando T, Iida Y, Nakamura H. Studies on saponins and sapogenins of ginseng: the structure of panaxatriol. Tetrahedron Lett 1965;42:207-213.
  3. Wagner-Jauregg T, Roth M. On panaxol, a new constituent of “red” ginseng root. Pharm Acta Helv 1962;37:352-359.
  4. Kanzaki T, Morisaki N, Shiina R, Saito Y. Role of transforming growth factor-beta pathway in the mechanism of wound healing by saponin from Ginseng Radix Rubra. Br J Pharmacol 1998;125:255-262. https://doi.org/10.1038/sj.bjp.0702052
  5. Choi S, Rho SH, Jung SY, Kim SC, Park CS, Nah SY. A novel activation of Ca(2+)-activated Cl(-) channel in Xenopus oocytes by Ginseng saponins: evidence for the involvement of phospholipase C and intracellular Ca(2+) mobilization. Br J Pharmacol 2001;132:641-648. https://doi.org/10.1038/sj.bjp.0703856
  6. Choi S, Kim HJ, Ko YS, Jeong SW, Kim YI, Simonds WF, Oh JW, Nah SY. G alpha(q/11) coupled to mammalian phospholipase C beta 3-like enzyme mediates the ginsenoside effect on Ca(2+)-activated Cl(-) current in the Xenopus oocyte. J Biol Chem 2001;276:48797-48802. https://doi.org/10.1074/jbc.M104346200
  7. Lee JH, Jeong SM, Lee BH, Kim JH, Ko SR, Kim SH, Lee SM, Nah SY. Effect of calmodulin on ginseng saponin-induced Ca2+-activated Cl- channel activation in Xenopus laevis oocytes. Arch Pharm Res 2005;28:413-420. https://doi.org/10.1007/BF02977670
  8. Reay JL, Kennedy DO, Scholey AB. Single doses of Panax ginseng (G115) reduce blood glucose levels and improve cognitive performance during sustained mental activity. J Psychopharmacol 2005;19:357-365. https://doi.org/10.1177/0269881105053286
  9. Wei XY, Yang JY, Wang JH, Wu CF. Anxiolytic effect of saponins from Panax quinquefolium in mice. J Ethnopharmacol 2007;111:613-618. https://doi.org/10.1016/j.jep.2007.01.009
  10. Eriksson TL, Svensson SP, Lundström I, Persson K, Andersson TP, Andersson RG. Panax ginseng induces anterograde transport of pigment organelles in Xenopus melanophores. J Ethnopharmacol 2008;119:17-23. https://doi.org/10.1016/j.jep.2008.05.024
  11. Lee JH, Jeong SM, Lee BH, Noh HS, Kim BK, Kim JI, Rhim H, Kim HC, Kim KM, Nah SY. Prevention of ginsenoside-induced desensitization of Ca2+-activated Clcurrent by microinjection of inositol hexakisphosphate in Xenopus laevis oocytes: involvement of GRK2 and betaarrestin I. J Biol Chem 2004;279:9912-9921. https://doi.org/10.1074/jbc.M310824200
  12. Jeong SM, Lee JH, Kim S, Rhim H, Lee BH, Kim JH, Oh JW, Lee SM, Nah SY. Ginseng saponins induce store-operated calcium entry in Xenopus oocytes. Br J Pharmacol 2004;142:585-593. https://doi.org/10.1038/sj.bjp.0705797
  13. Dascal N. The use of Xenopus oocytes for the study of ion channels. CRC Crit Rev Biochem 1987;22:317-387. https://doi.org/10.3109/10409238709086960
  14. Berridge MJ, Bootman MD, Roderick HL. Calcium signalling: dynamics, homeostasis and remodelling. Nat Rev Mol Cell Biol 2003;4:517-529. https://doi.org/10.1038/nrm1155
  15. Yamamoto Y, Nunome T, Yamauchi R, Kato K, Sone Y. Structure of an exocellular polysaccharide of Lactobacillus helveticus TN-4, a spontaneous mutant strain of Lactobacillus helveticus TY1-2. Carbohydr Res 1995;275:319-332. https://doi.org/10.1016/0008-6215(95)00077-7
  16. Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970;227:680-685. https://doi.org/10.1038/227680a0
  17. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976;72:248-254. https://doi.org/10.1016/0003-2697(76)90527-3
  18. Walker JM. The protein protocols handbook. Totawa: Humana press, 1996.
  19. Scott TA, Melvin EH. Determination of dextran with anthrone. Anal Chem 1953;25:1656-1660. https://doi.org/10.1021/ac60083a023
  20. Jorgensen NK, Petersen SF, Hoffmann EK. Thrombin-, bradykinin-, and arachidonic acid-induced Ca2+ signaling in Ehrlich ascites tumor cells. Am J Physiol 1999;276(1Pt 1):C26-C37. https://doi.org/10.1152/ajpcell.1999.276.1.C26
  21. Grynkiewicz G, Poenie M, Tsien RY. A new generation of Ca2+ indicators with greatly improved fl uorescence properties. J Biol Chem 1985;260:3440-3450.
  22. Dobrydneva Y, Blackmore P. 2-Aminoethoxydiphenyl borate directly inhibits store-operated calcium entry channels in human platelets. Mol Pharmacol 2001;60:541-552.
  23. Yoon JY, Ha BH, Woo JS, Lim YH, Kim KH. Purification and characterization of a 28-kDa major protein from ginseng root. Comp Biochem Physiol B Biochem Mol Biol 2002;132:551-557. https://doi.org/10.1016/S1096-4959(02)00070-2
  24. Abdrasilov BS, Kim YuA, Nurieva RI, Dedkova EN, Leonteva GA, Park HJ, Zinchenko VP. The effect of total saponins from Panax ginseng C. A. Meyer on the intracellular signalling system in Ehrlich ascites tumor cells. Biochem Mol Biol Int 1996;38:519-526.
  25. Choi S, Lee JH, Kim YI, Kang MJ, Rhim H, Lee SM, Nah SY. Effects of ginsenoside on G protein-coupled inwardly rectifying $K^+$ channel activity expressed in Xenopus oocytes. Eur J Pharmacol 2003;468:83-92. https://doi.org/10.1016/S0014-2999(03)01666-2

Cited by

  1. Gintonin, newly identified compounds from ginseng, is novel lysophosphatidic acids-protein complexes and activates G protein-coupled lysophosphatidic acid receptors with high affinity vol.33, pp.2, 2012, https://doi.org/10.1007/s10059-012-2216-z
  2. Gintonin, a ginseng-derived novel ingredient, evokes long-term potentiation through N-methyl-D-aspartic acid receptor activation: Involvement of LPA receptors vol.34, pp.6, 2012, https://doi.org/10.1007/s10059-012-0254-4
  3. Suppression of metastasis of intravenously-inoculated B16/F10 melanoma cells by the novel ginseng-derived ingredient, gintonin: Involvement of autotaxin inhibition vol.42, pp.1, 2012, https://doi.org/10.3892/ijo.2012.1709
  4. -Activated Potassium Channel Activation by Ginseng Gintonin vol.2013, pp.1741-4288, 2013, https://doi.org/10.1155/2013/323709
  5. Yin and Yang of ginseng pharmacology: ginsenosides vs gintonin vol.34, pp.11, 2013, https://doi.org/10.1038/aps.2013.100
  6. Gintonin, a ginseng-derived lysophosphatidic acid receptor ligand, potentiates ATP-gated P2X1 receptor channel currents vol.35, pp.2, 2013, https://doi.org/10.1007/s10059-013-2293-x
  7. Ginseng Gintonin Activates the Human Cardiac Delayed Rectifier K+ Channel: Involvement of Ca2+/Calmodulin Binding Sites vol.37, pp.9, 2014, https://doi.org/10.14348/molcells.2014.0087
  8. Oral Administration of Gintonin Attenuates Cholinergic Impairments by Scopolamine, Amyloid-β Protein, and Mouse Model of Alzheimer’s Disease vol.38, pp.9, 2015, https://doi.org/10.14348/molcells.2015.0116
  9. Structure of ginseng major latex-like protein 151 and its proposed lysophosphatidic acid-binding mechanism vol.71, pp.5, 2015, https://doi.org/10.1107/S139900471500259X
  10. Gintonin facilitates catecholamine secretion from the perfused adrenal medulla vol.20, pp.6, 2016, https://doi.org/10.4196/kjpp.2016.20.6.629
  11. A Role of Ginseng and Its Constituents in the Treatment of Central Nervous System Disorders vol.2016, pp.1741-4288, 2016, https://doi.org/10.1155/2016/2614742
  12. Green corrosion inhibitors for aluminium and its alloys: a review vol.7, pp.44, 2017, https://doi.org/10.1039/C7RA03944A
  13. Gintonin, a Ginseng-Derived Exogenous Lysophosphatidic Acid Receptor Ligand, Protects Astrocytes from Hypoxic and Re-oxygenation Stresses Through Stimulation of Astrocytic Glycogenolysis pp.1559-1182, 2019, https://doi.org/10.1007/s12035-018-1308-1
  14. impaired glycoprotein VI signaling pp.1369-1635, 2018, https://doi.org/10.1080/09537104.2018.1479033
  15. Gintonin Mitigates MPTP-Induced Loss of Nigrostriatal Dopaminergic Neurons and Accumulation of α-Synuclein via the Nrf2/HO-1 Pathway pp.1559-1182, 2018, https://doi.org/10.1007/s12035-018-1020-1
  16. A Simple Method for the Preparation of Crude Gintonin from Ginseng Root, Stem, and Leaf vol.35, pp.2, 2011, https://doi.org/10.5142/jgr.2011.35.2.209
  17. An Edible Gintonin Preparation from Ginseng vol.35, pp.4, 2011, https://doi.org/10.5142/jgr.2011.35.4.471
  18. Preparation of a Monoclonal Antibody against Gintonin and Its Use in an Enzyme Immunoassay vol.38, pp.10, 2015, https://doi.org/10.1248/bpb.b15-00171
  19. Ginseng pharmacology: a new paradigm based on gintonin-lysophosphatidic acid receptor interactions vol.6, pp.None, 2011, https://doi.org/10.3389/fphar.2015.00245
  20. Functional role of ginseng-derived compounds in cancer vol.42, pp.3, 2018, https://doi.org/10.1016/j.jgr.2017.04.009
  21. Gintonin Enhances Proliferation, Late Stage Differentiation, and Cell Survival From Endoplasmic Reticulum Stress of Oligodendrocyte Lineage Cells vol.10, pp.None, 2011, https://doi.org/10.3389/fphar.2019.01211
  22. Purification and identification of a novel protein isolated from Panax quinquefolium and evaluation of its In vitro antioxidant properties vol.5, pp.4, 2011, https://doi.org/10.4103/wjtcm.wjtcm_20_19