Journal of Ginseng Research

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

DOI QR Code

Bioactive lipids in gintonin-enriched fraction from ginseng

  • Cho, Hee-Jung (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University) ;
  • Choi, Sun-Hye (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University) ;
  • Kim, Hyeon-Joong (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University) ;
  • Lee, Byung-Hwan (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University) ;
  • Rhim, Hyewon (Center for Neuroscience, Korea Institute of Science and Technology) ;
  • Kim, Hyoung-Chun (Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University) ;
  • Hwang, Sung-Hee (Department of Pharmaceutical Engineering, College of Health Sciences, Sangji University) ;
  • Nah, Seung-Yeol (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University)
  • Received : 2017.09.19
  • Accepted : 2017.11.16
  • Published : 2019.04.15
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Ginseng is a traditional herbal medicine for human health. Ginseng contains a bioactive ligand named gintonin. The active ingredient of gintonin is lysophosphatidic acid C18:2 (LPA C18:2). We previously developed a method for gintonin-enriched fraction (GEF) preparation to mass-produce gintonin from ginseng. However, previous studies did not show the presence of other bioactive lipids besides LPAs. The aim of this study was to quantify the fatty acids, lysophospholipids (LPLs), and phospholipids (PLs) besides LPAs in GEF. Methods: We prepared GEF from white ginseng. We used gas chromatography-mass spectrometry for fatty acid analysis and liquid chromatography-tandem mass spectrometry for PL analysis, and quantified the fatty acids, LPLs, and PLs in GEF using respective standards. We examined the effect of GEF on insulin secretion in INS-1 cells. Results: GEF contains about 7.5% linoleic (C18:2), 2.8% palmitic (C16:0), and 1.5% oleic acids (C18:1). GEF contains about 0.2% LPA C18:2, 0.06% LPA C16:0, and 0.02% LPA C18:1. GEF contains 0.08% lysophosphatidylcholine, 0.03% lysophosphatidylethanolamine, and 0.13% lysophosphatidylinositols. GEF also contains about 1% phosphatidic acid (PA) 16:0-18:2, 0.5% PA 18:2-18:2, and 0.2% PA 16:0-18:1. GEFmediated insulin secretion was not blocked by LPA receptor antagonist. Conclusion: We determined four characteristics of GEF through lipid analysis and insulin secretion. First, GEF contains a large amount of linoleic acid (C18:2), PA 16:0-18:2, and LPA C18:2 compared with other lipids. Second, the main fatty acid component of LPLs and PLs is linoleic acid (C18:2). Third, GEF stimulates insulin secretion not through LPA receptors. Finally, GEF contains bioactive lipids besides LPAs.

Keywords

References

  1. Brekhman II , Dardymov IV . New substances of plant origin which increase nonspecific resistance. Annu Rev Pharmacol 1969;9:419-30. https://doi.org/10.1146/annurev.pa.09.040169.002223
  2. Nah SY. Ginseng ginsenoside pharmacology in the nervous system: involvement in the regulation of ion channels and receptors. Front Physiol 2014;5:98. https://doi.org/10.3389/fphys.2014.00098
  3. Nah SY, Kim DH, Rhim H. Ginsenosides: are any of them candidates for drugs acting on the central nervous system? CNS Drug Rev 2007;13:381-404. https://doi.org/10.1111/j.1527-3458.2007.00023.x
  4. Cho IH. Effects of Panax ginseng in neurodegenerative diseases. J Ginseng Res 2012;36:342-53. https://doi.org/10.5142/jgr.2012.36.4.342
  5. Loh SH, Park JY, Cho EH, Nah SY, Kang YS. Animal lectins: potential receptors for ginseng polysaccharides. J Ginseng Res 2017;41:1-9. https://doi.org/10.1016/j.jgr.2015.12.006
  6. 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
  7. Hwang SH, Shin TJ, Choi SH, Cho HJ, Lee B-H, 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
  8. Chen X, Snyder CL, Truksa M, Shah S, Weselake RJ. sn-Glycerol-3-phosphate acyltransferases in plants. Plant Signal Behav 2011;6:1695-9. https://doi.org/10.4161/psb.6.11.17777
  9. Lee BH, Choi SH, Kim HJ, Jung SW, Kim HK, Nah SY. Plant lysophosphatidic acids: a rich source for bioactive lysophosphatidic acids and their pharmacological applications. Biol Pharm Bull 2016;39:156-62. https://doi.org/10.1248/bpb.b15-00575
  10. Choi SH, Jung SW, Kim HS, Kim HJ, Lee BH, Kim JY, Kim JH, Hwang SH, Rhim H, Kim HC, et al. A brief method for preparation of gintonin-enriched fraction from ginseng. J Ginseng Res 2015;39:398-405. https://doi.org/10.1016/j.jgr.2015.05.002
  11. Kim HJ, Shin EJ, Lee BH, Choi SH, Jung SW, Cho IH, Hwang SH, Kim JY, Han JS, Chung C, et al. Oral administration of gintonin attenuates cholinergic impairments by scopolamine, amyloid-b protein, and mouse model of Alzheimer's disease. Mol Cells 2015;38:796-805. https://doi.org/10.14348/molcells.2015.0116
  12. Kim HJ, Kim DJ, Shin EJ, Lee BH, Choi SH, Hwang SH, Rhim H, Cho IH, Kim HC, Nah SY. Effects of gintonin-enriched fraction on hippocampal cell proliferation in wild-type mice and an APPswe/PSEN-1 double Tg mouse model of Alzheimer's disease. Neurochem Int 2016;101:56-65. https://doi.org/10.1016/j.neuint.2016.10.006
  13. Kim HJ, Park SD, Lee RM, Lee BH, Choi SH, Hwang SH, Rhim H, Kim HC, Nah SY. Gintonin attenuates depressive-like behaviors associated with alcohol withdrawal in mice. J Affect Disord 2017;215:23-9. https://doi.org/10.1016/j.jad.2017.03.026
  14. Lee BH, Kim HK, Jang M, Kim HJ, Choi SH, Hwang SH, Kim HC, Rhim H, Cho IH, Nah SY. Effects of gintonin-enriched fraction in an atopic dermatitis animal model: involvement of autotaxin regulation. Biol Pharm Bull 2017;40:1063-70. https://doi.org/10.1248/bpb.b17-00124
  15. Chung SWC, Tong SK, Xiao Y, Ho YY. Methylmercury and long-chain n-3 fatty acids of 88 fish species commonly consumed in Hong Kong. J Anal Sci and Technol 2015:1-9.
  16. Yoon HR, Kim H, Cho SH. Quantitative analysis of acyl-lysophosphatidic acid in plasma using negative ionization tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2003;788:85-92. https://doi.org/10.1016/S1570-0232(02)01031-0
  17. Choi SE, Shin HC, Kim HE, Lee SJ, Jang HJ, Lee KW, Kang Y. Involvement of $Ca^{2+}$, CaMK II and PKA in EGb 761-induced insulin secretion in INS-1 cells. J Ethnopharmacol 2007;110:49-55. https://doi.org/10.1016/j.jep.2006.09.001
  18. Makide K, Uwamizu A, Shinjo Y, Ishiguro J, Okutani M, Inoue A, Aoki J. Novel lysophospholipid receptors: their structure and function. J Lipid Res 2014;55: 1986-95. https://doi.org/10.1194/jlr.R046920
  19. Laprairie RB, Bagher AM, Denovan-Wright EM. Cannabinoid receptor ligand bias: implications in the central nervous system. Curr Opin Pharmacol 2017;32:32-43. https://doi.org/10.1016/j.coph.2016.10.005
  20. Choi SH, Jung SW, Lee BH, Kim HJ, Hwang SH, Kim HK, Nah SY. Ginseng pharmacology: a new paradigm based on gintonin-lysophosphatidic acid receptor interactions. Front Pharmacol 2015;6:245.
  21. Zhang XJ, Huang LL, Cai XJ, Li P, Wang YT, Wan JB. Fatty acid variability in three medicinal herbs of Panax species. Chem Cent J 2013;7:12. https://doi.org/10.1186/1752-153X-7-12
  22. Raho N, Ramirez L, Lanteri ML, Gonorazky G, Lamattina L, ten Have A, Laxalt AM. Phosphatidic acid production in chitosan-elicited tomato cells, via both phospholipase D and phospholipase C/diacylglycerol kinase, requires nitric oxide. J Plant Physiol 2011;168:534-9. https://doi.org/10.1016/j.jplph.2010.09.004
  23. Foster DA. Regulation of mTOR by phosphatidic acid? Cancer Res 2007;67:1-4. https://doi.org/10.1158/0008-5472.CAN-06-3016
  24. Kim HU, Huang AH. Plastid lysophosphatidyl acyltransferase is essential for embryo development in Arabidopsis. Plant Physiol 2004;134:1206-16. https://doi.org/10.1104/pp.103.035832
  25. Tanaka T, Kassai A, Ohmoto M, Morito K, Kashiwada Y, Takaishi Y, Urikura M, Morishige J, Satouchi K, Tokumura A. Quantification of phosphatidic acid in foodstuffs using a thin-layer-chromatography-imaging technique. J Agric Food Chem 2012;60:4156-61. https://doi.org/10.1021/jf300147y
  26. Yamashima T. Dual effects of the non-esterified fatty acid receptor 'GPR40' for human health. Prog Lipid Res 2015;58:40-50. https://doi.org/10.1016/j.plipres.2015.01.002
  27. Cunnane SC. Problems with essential fatty acids: time for a new paradigm? Progr Lipid Res 2003;42:544-68. https://doi.org/10.1016/S0163-7827(03)00038-9
  28. Testerink C, Munnik T. Molecular, cellular, and physiological responses to phosphatidic acid formation in plants. J Exp Bot 2011;62:2349-61. https://doi.org/10.1093/jxb/err079
  29. Fang Y, Vilella-Bach M, Bachmann R, Flanigan A, Chen J. Phosphatidic acidmediated mitogenic activation of mTOR signaling. Science 2001;294:1942-5. https://doi.org/10.1126/science.1066015
  30. Menon D, Salloum D, Bernfeld E, Gorodetsky E, Akselrod A, Frias MA, Sudderth J, Chen PH, DeBerardinis R, Foster DA. Lipid sensing by mTOR complexes via de novo synthesis of phosphatidic acid. J Biol Chem 2017;292: 6303-11. https://doi.org/10.1074/jbc.M116.772988
  31. Foster DA. Phosphatidic acid and lipid-sensing by mTOR. Trends Endocrinol Metab 2013;24:272-8. https://doi.org/10.1016/j.tem.2013.02.003
  32. Joy JM, Gundermann DM, Lowery RP, Jager R, McCleary SA, Purpura M, Roberts MD, Wilson SM, Hornberger TA, Wilson JM. Phosphatidic acid enhances mTOR signaling and resistance exercise induced hypertrophy. Nutr Metab 2014;11:29. https://doi.org/10.1186/1743-7075-11-29
  33. Choi KJ, Kim MW, Kim DH. Studies on the lipid components of various ginsengs I. Lipid and fatty acid compositions of the free lipids. Korean J Ginseng Sci 1985;9:193-203.
  34. D'Angeli S, Altamura MM. Unsaturated lipids change in olive tree drupe and seed during fruit development and in response to cold-stress and acclimation. Int J Mol Sci 2016;12(17):1889.
  35. Arisz SA, Munnik T. Distinguishing phosphatidic acid pools from de novo synthesis, PLD, and DGK. Methods Mol Biol 2013;1009:55-62. https://doi.org/10.1007/978-1-62703-401-2_6

Cited by

  1. Gintonin modulates platelet function and inhibits thrombus formation via impaired glycoprotein VI signaling vol.30, pp.5, 2019, https://doi.org/10.1080/09537104.2018.1479033
  2. Ginseng Gintonin Enhances Hyaluronic Acid and Collagen Release from Human Dermal Fibroblasts Through Lysophosphatidic Acid Receptor Interaction vol.24, pp.24, 2019, https://doi.org/10.3390/molecules24244438
  3. Effects of Gintonin-Enriched Fraction on Methylmercury-Induced Neurotoxicity and Organ Methylmercury Elimination vol.17, pp.3, 2019, https://doi.org/10.3390/ijerph17030838
  4. Gintonin-Enriched Fraction Suppresses Heat Stress-Induced Inflammation through LPA Receptor vol.25, pp.5, 2019, https://doi.org/10.3390/molecules25051019
  5. Ginseng Gintonin Contains Ligands for GPR40 and GPR55 vol.25, pp.5, 2019, https://doi.org/10.3390/molecules25051102
  6. Ginseng gintonin, aging societies, and geriatric brain diseases vol.10, pp.1, 2021, https://doi.org/10.1016/j.imr.2020.100450
  7. Protective Effects of Gintonin on Reactive Oxygen Species-Induced HT22 Cell Damages: Involvement of LPA1 Receptor-BDNF-AKT Signaling Pathway vol.26, pp.14, 2019, https://doi.org/10.3390/molecules26144138
  8. Inhibitory activity of gintonin on inflammation in human IL-1β-stimulated fibroblast-like synoviocytes and collagen-induced arthritis in mice vol.45, pp.4, 2021, https://doi.org/10.1016/j.jgr.2020.12.001