Gintonin Explained

Uniprot:	B5THI3
Major latex-like protein
Symbol:	mlp151
Organism:	Panax ginseng

Gintonin is a glycolipoprotein fraction isolated from Panax ginseng. The non-saponin ingredient was designated as gintonin, where gin was derived from ginseng, ton from the tonic effects of ginseng, and in from protein. The main component of gintonin is a complex of lysophosphatidic acids (LPA) and ginseng proteins such as ginseng major latex-like protein151 (GLP151) and ginseng ribonuclease-like storage protein.^{[1] [2]}

GLP151 is a first plant-derived LPA binding protein as one of Bet v 1 superfamily. GLP151 has a LPA binding domain on H147 and H148 at C-terminal. These two histidine residues bind to phosphate group of LPA.^[3]

Biological action

Gintonin is believed to act by delivering LPA to lysophospholipid receptors, which are high affinity and selective target receptors. In animal cell cultures, gintonin induces [Ca²⁺] transients via activation of the said receptor.^[3]

One Korean study claims that gintonin is orally active in rodents and shows anti-Alzheimer's disease effects through LPA receptor-mediated non-amyloidogenic pathways.^{[4] [5]} Oral gintonin is well-tolerated by human AD patients in a small study, but the benefits are unclear.^[6]

A number of other effects are attributed to oral administration of gintonin-enriched extract in rodents.^{[7] [8] [9] [10]}

See also

• Ginseng
• Ginsenoside
• Lysophosphatidic acid
• Lysophospholipid receptor

Further reading

• Pyo . M. K. . Choi . S. H. . Hwang . S. H. . Shin . T. J. . Lee . B. H. . Lee . S. M. . Lim . Y. H. . Kim . D. H. . Nah . S. Y. . Novel Glycolipoproteins from Ginseng . 10.5142/jgr.2011.35.1.092 . Journal of Ginseng Research . 35 . 92–103 . 2011 . free .
• Pyo . M. K. . Choi . S. H. . Shin . T. J. . Hwang . S. H. . Lee . B. H. . Kang . J. Y. . Kim . H. J. . Lee . S. H. . Nah . S. Y. . 10.5142/jgr.2011.35.2.209 . A Simple Method for the Preparation of Crude Gintonin from Ginseng Root, Stem, and Leaf . Journal of Ginseng Research . 35 . 2 . 209–218 . 2011 . 23717063. 3659522 .
• Choi . S. H. . Shin . T. J. . Lee . B. H. . Hwang . S. H. . Kang . J. Y. . Kim . H. J. . Park . C. W. . Nah . S. Y. . 10.5142/jgr.2011.35.4.471 . An Edible Gintonin Preparation from Ginseng . Journal of Ginseng Research . 35 . 4 . 471–478 . 2011 . 23717094. 3659555 .
• Hwang . S. H. . Shin . T. J. . Choi . S. H. . Cho . H. J. . Lee . B. H. . Pyo . M. K. . Lee . J. H. . Kang . J. . Kim . H. J. . Park . C. W. . Shin . H. C. . Nah . S. Y. . 10.1007/s10059-012-2216-z . Gintonin, newly identified compounds from ginseng, is novel lysophosphatidic acids-protein complexes and activates G protein-coupled lysophosphatidic acid receptors with high affinity . Molecules and Cells . 33 . 2 . 151–162 . 2012 . 22286231. 3887723.
• 10.3233/JAD-2012-120439. 22543851. Gintonin, a ginseng-derived lysophosphatidic acid receptor ligand, attenuates Alzheimer's disease-related neuropathies: involvement of non-amyloidogenic processing. Journal of Alzheimer's Disease. 31. 1. 207–223. 2012. Hwang SH. Shin EJ, Shin TJ, Lee BH, Choi SH, Kang J, Kim HJ, Kwon SH, Jang CG, Lee JH, Kim HC, Nah SY.
• 23017203. 2012. Nah. S. Y.. Gintonin: A novel ginseng-derived ligand that targets G protein- coupled lysophosphatidic acid receptors. Current Drug Targets. 13. 13. 1659–64 . 10.2174/138945012803529947.
• 10.1007/s10059-012-0254-4. 23161173. Gintonin, a ginseng-derived novel ingredient, evokes long-term potentiation through N-methyl-D-aspartic acid receptor activation: Involvement of LPA receptors. Molecules and Cells. 34. 6. 563–72. 2012. Shin . T. J. . Kim . H. J. . Kwon . B. J. . Choi . S. H. . Kim . H. B. . Hwang . S. H. . Lee . B. H. . Lee . S. M. . Zukin . R. S. . Park . J. H. . Kim . H. C. . Rhim . H. . Lee . J. H. . Nah . S. Y. . 3887827.
• 10.1007/s10059-013-2293-x. 23456336. 3887903. Gintonin, a ginseng-derived lysophosphatidic acid receptor ligand, potentiates ATP-gated P2X1 receptor channel currents. Molecules and Cells. 35. 2. 142–50. 2013. Choi . S. H. . Kim . H. J. . Kim . B. R. . Shin . T. J. . Hwang . S. H. . Lee . B. H. . Lee . S. M. . Rhim . H. . Nah . S. Y. .
• 10.1155/2013/323709. 23662129. Molecular Mechanisms of Large-Conductance Ca2+-Activated Potassium Channel Activation by Ginseng Gintonin. Evidence-Based Complementary and Alternative Medicine. 2013. 1–14. 2013. Choi . S. H.. Lee . B. H.. Hwang . S. H.. Kim . H. J.. Lee . S. M.. Kim . H. C.. Rhim . H. W.. Nah . S. Y.. 3638619. free.
• 10.1016/j.neulet.2013.05.048. 23769686. Activation of lysophosphatidic acid receptor by gintonin inhibits Kv1.2 channel activity: Involvement of tyrosine kinase and receptor protein tyrosine phosphatase α. Neuroscience Letters. 548. 143–8. 2013. Lee . J. H. . Choi . S. H. . Lee . B. H. . Hwang . S. H. . Kim . H. J. . Rhee . J. . Chung . C. . Nah . S. Y. .
• 10.1038/aps.2013.100. 24122014. Yin and Yang of ginseng pharmacology: Ginsenosides vs gintonin. Acta Pharmacologica Sinica. 34. 11. 1367–73. 2013. Im . D. S. . Nah . S. Y. . 3818586.
• 10.1159/000366306. 25199952. Characteristics of Gintonin-Mediated Membrane Depolarization of Pacemaker Activity in Cultured Interstitial Cells of Cajal. Cellular Physiology and Biochemistry. 34. 3. 873–90. 2014. Kim . B. J. . Nam . J. H. . Kim . K. H. . Joo . M. . Ha . T. S. . Weon . K. Y. . Choi . S. . Jun . J. Y. . Park . E. J. . Wie . J. . So . I. . Nah . S. Y. . free .
• 10.14348/molcells.2014.0087. Ginseng Gintonin Activates the Human Cardiac Delayed Rectifier K+ Channel: Involvement of Ca2+/Calmodulin Binding Sites. Molecules and Cells. 2014. Sun-Hye Choi . B. H. Lee. Kim HJ, Jung SW, Kim HS, Shin HC, Lee JH, Kim HC, Rhim H, Hwang SH, Ha TS, Kim HJ, Cho H, Nah SY. 25234465. 37. 9. 656–63. 4179134.
• Hwang . SH . Lee . BH . Choi . SH . Jung . SW . Kim . HS . Shin . HC . Park . HJ . Park . KH . Lee . MK . Nah . SY . 2015 . Gintonin, a novel ginseng-derived lysophosphatidic acid receptor ligand, stimulates neurotransmitter release . Neuroscience Letters . 584 . 356–61 . 10.1016/j.neulet.2014.11.007 . 25445364 .
• Park . H . Kim . s . Rhee . J . Kim . HJ . Han . JS . Nah . SY . Chung . C . 2015 . Synaptic enhancement induced by gintonin via lysophosphatidic acid receptor activation in central synapses . Journal of Neurophysiology . 113 . 5 . 1493–500 . 25505112 . 10.1152/jn.00667.2014 .
• Choi . SH . Hong . MK . Kim . HJ . Ryoo . N . Rhim . H . Nah . SY . Kang . LW . 2015 . Structure of ginseng major latex-like protein 151 and its proposed lysophosphatidic acid-binding mechanism . Acta Crystallographica Section D . 71 . pt5 . 1039–50 . 25945569 . 10.1107/S139900471500259X .
• Kim . H . Lee . BH . Choi . SH . Kim . HJ . Jung . SW . Hwang . SH . Rhim . H . Kim . HC . Cho . IH . Nah . SY . 2015 . Gintonin stimulates gliotransmitter release in cortical primary astrocytes . Neuroscience Letters . 603 . 19–24 . 26191656 . 10.1016/j.neulet.2015.07.012.
• Kim . HJ . Shin . EJ . Lee . BH . Choi . SH . Jung . SW . Cho . IH . Hwang . SH . Kim . JY . Han . JS . Chung . C . Jang . CG . Rhim . H . Kim . HC . Nah . SY . 2015 . Oral Administration of Gintonin Attenuates Cholinergic Impairments by Scopolamine, Amyloid-β Protein, and Mouse Model of Alzheimer's Disease . Molecules and Cells . 38. 9. 796–805. 26255830 . 10.14348/molcells.2015.0116 . 4588723.
• Lee . BH . Choi . SH . Kim . HJ . Jung . SW . Kim . H . Shin . HC . Lee . JH . Hwang . SH . Kim . HC . Nah . SY . 2015 . Preparation of a Monoclonal Antibody against Gintonin and Its Use in an Enzyme Immunoassay. Biological and Pharmaceutical Bulletin . 38 . 10 . 1631–37 . 26424022. 10.1248/bpb.b15-00171. free .
• Choi . SH . Jung . SW . Kim . H . Kim . HJ . Lee . BH . Kim . JY . Kim . JH . Hwang . SH . Rhim . H . Nah . SY . 2015 . A Brief method for preparation of gintonin-enriched fraction from ginseng . Journal of Ginseng Research . 39 . 4. 398–405 . 26869834. 10.1016/j.jgr.2015.05.002. 4593782 .
• 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 . 10.1016/j.neuint.2016.10.006 . Neurochemistry International . 101 . 56–65 . 2016 . 27765516.
• Hwang . SH . Lee . BH . Choi . SH . Kim . HJ . Won . KJ . Lee . HM . Rhim . H . Kim . HC . Nah . SY . Effects of gintonin on the proliferation, migration, and tube formation of human umbilical-vein endothelial cells: involvement of lysophosphatidic-acid receptors and vascular-endothelial-growth-factor signaling . 10.1016/j.jgr.2015.10.002 . Journal of Ginseng Research . 40 . 4 . 325–333 . 2016 . 27746684. 5052429 .
• Nah . SY . Kim . KH . Choi . MS . Ha . KS . Lim . DY . Gintonin facilitates catecholamine secretion from the perfused adrenal medulla . 10.4196/kjpp.2016.20.6.629 . Korean J Physiol Pharmacol . 20 . 6 . 629–639 . 2016 . 27847440. 5106397 .
• 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 . 10.1016/j.jad.2017.03.026 . J Affect Disord . 215 . 23–29 . 2017 . 28314177 .
• Lee. BH . Kim . HK . Jang . M . Kim . HJ . Choi . SH . Hwang . SH . Kim . HC . Rhim . H . Choi . IH . Nah . SY . Effects of Gintonin-Enriched Fraction in an Atopic Dermatitis Animal Model: Involvement of Autotaxin Regulation . 10.1248/bpb.b17-00124 . Biol Pharm Bull . 40. 7 . 1063–1070 . 2017 . 28674249 . free .
• 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 . 10.1248/bpb.b17-00124 . Biological and Pharmaceutical Bulletin . 40 . 7 . 1063–70 . 2017 . 28674249 . free .
• Moon J . Choi SH . Shim JY . Park HJ . Oh MJ . Kim M . Nah SY . EGintonin Administration Is Safe and Potentially Beneficial in Cognitively Impaired Elderly . 10.1097/WAD.0000000000000213 . Alzheimer Dis Assoc Disord . 32 . 1 . 85–87 . 2018 . 29028648 .
• Lee BH . Choi SH . Kim HJ . Park SD . Rhim H . Kim HC . Hwang SH . Nah SY . Gintonin Absorption in Intestinal Model Systems . 10.1016/j.jgr.2016.12.007 . J Ginseng Res . 42 . 1 . 35–41 . 2018 . 29348720 . 5766688 . free .
• Kim DG . Jang M . Choi SH . Kim HJ . Jhun H . Kim HC . Rhim H . Cho IH . Nah SY. Gintonin, a Ginseng-Derived Exogenous Lysophosphatidic Acid Receptor Ligand, Enhances Blood-Brain Barrier Permeability and Brain Delivery . 10.1016/j.ijbiomac.2018.03.158 . Int J Biol Macromol. 114 . 1325–1337 . 2018 . 29604355 .
• Choi JH. Jang M . Oh S . Nah SY . Cho IH . Multi-Target Protective Effects of Gintonin in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Mediated Model of Parkinson's Disease via Lysophosphatidic Acid Receptors . 10.3389/fphar.2018.00515 . Front Pharmacol. 9 . 515 . 2018 . 29875659 . 5974039 . free .
• Choi SH . Kim HJ . Cho HJ . Park SD . Lee NE . Hwang SH . Cho IH . Hwang H . Rhim H . Kim HC . Nah SY . Gintonin, a Ginseng-Derived Exogenous Lysophosphatidic Acid Receptor Ligand, Protects Astrocytes From Hypoxic and Re-oxygenation Stresses Through Stimulation of Astrocytic Glycogenolysis . 10.1007/s12035-018-1308-1 . Mol Neurobiol . 56 . 5 . 3280–3294 . 2019 . 30117105 .
• Nam SM . Hwang H . Seo M . Chang BJ . Kim HJ . Choi SH . Rhim H . Kim HC . Cho IH . Nah SY . Gintonin Attenuates D-Galactose-Induced Hippocampal Senescence by Improving Long-Term Hippocampal Potentiation, Neurogenesis, and Cognitive Functionss . 10.1159/000491113 . Gerontology . 64 . 6 . 562–575 . 2018 . 30138913 .
• Kim HJ . Jung SW . Kim SY . Cho IH . Kim HC . Rhim H . Kim M . Nah SY . Panax Ginseng as an Adjuvant Treatment for Alzheimer's Disease . 10.1016/j.jgr.2017.12.008 . J Ginseng Res . 42 . 4 . 401–411 . 2018 . 30337800 . 6190533 . free .
• Jo MG . Ikram M . Jo MH . Yoo L . Chung KC . Nah SY . Hwang H . Rhim H . Kim MO . Nah SY . Gintonin Mitigates MPTP-Induced Loss of Nigrostriatal Dopaminergic Neurons and Accumulation of α-Synuclein via the Nrf2/HO-1 Pathway . 10.1007/s12035-018-1020-1 . Mol Neurobiol . 56 . 1 . 39–55 . 2019 . 29675576 .
• Irfan M . Jeong D . Saba E . Kwon HW . Shin JH . Jeon BR . Kim S . Kim SD . Lee DH . Nah SY . Rhee MH . Gintonin Modulates Platelet Function and Inhibits Thrombus Formation via Impaired Glycoprotein VI Signaling . 10.1080/09537104.2018.1479033 . Platelets . 30 . 5 . 589–598 . 2019 . 29870296 .
• Jang M . Choi JH . Chang Y . Lee SJ . Nah SY . Cho IH . Gintonin, a Ginseng-Derived Ingredient, as a Novel Therapeutic Strategy for Huntington's Disease: Activation of the Nrf2 Pathway Through Lysophosphatidic Acid Receptors . 10.1016/j.bbi.2019.03.001 . Brain Behav Immun . 80 . 146–162 . 2019 . 30853569 .
• Cho HJ . Choi SH . Kim HJ . Lee BH . Rhim H . Kim HC . Hwang SH . Nah SY . Bioactive Lipids in Gintonin-Enriched Fraction From Ginseng . 10.1016/j.jgr.2017.11.006 . J Ginseng Res . 43 . 2 . 209–217 . 2019 . 30962735 . 6437394 . free .
• Choi SH . Kim HJ . Cho HJ . Park SD . Lee NE . Hwang SH . Rhim H . Kim HC . Cho IH . Nah SY . Gintonin-mediated Release of Astrocytic Vascular Endothelial Growth Factor Protects Cortical Astrocytes From Hypoxia-Induced Cell Damages . 10.1016/j.jgr.2018.05.006 . J Ginseng Res . 43 . 2 . 305–311 . 2019 . 30976168 . 6437663 . free .
• Mijan MA . Kim JY . Moon SY . Choi SH . Nah SY . Yang HJ . Gintonin Enhances Proliferation, Late Stage Differentiation, and Cell Survival From Endoplasmic Reticulum Stress of Oligodendrocyte Lineage Cells . 10.3389/fphar.2019.01211 . Front Pharmacol . 10 . 1211 . 2019 . 31680979 . 6797839 . free .
• Lee R . Lee NE . Hwang H . Rhim H . Cho IH . Nah SY . Ginseng Gintonin Enhances Hyaluronic Acid and Collagen Release From Human Dermal Fibroblasts Through Lysophosphatidic Acid Receptor Interaction . 10.3390/molecules24244438 . Molecules . 24 . 24 . 4438 . 2019 . 31817172 . 6943507 . free .
• Kim HJ . Choi SH . Lee NE . Cho HJ . Rhim H . Kim HC . Hwang SH . Nah SY . Effects of Gintonin-Enriched Fraction on Methylmercury-Induced Neurotoxicity and Organ Methylmercury Elimination . 10.3390/ijerph17030838 . Int J Environ Res Public Health . 17 . 3 . 838 . 2020 . 32013120 . 7038146 . free .
• Lee NE . Park SD . Hwang H . Choi SH . Lee RM . Nam SM . Choi JH . Rhim H . Cho IH . Kim HC . Hwang SH . Nah SY . Effects of a Gintonin-Enriched Fraction on Hair Growth: An in vitro and in vivo Study . 10.1016/j.jgr.2019.05.013 . J Ginseng Res . 44 . 1 . 168–177 . 2020 . 32095099 . 7033365 . free .
• Chei S . Song JH . Oh HJ . Lee K . Jin H . Choi SH . Nah SY . Lee BY . Gintonin-Enriched Fraction Suppresses Heat Stress-Induced Inflammation Through LPA Recepto . 10.3390/molecules25051019 . Molecules . 25 . 5 . 1019 . 2020 . 32106493 . 7179209 . free .
• Cho YJ . Choi SH . Lee R . Hwang H. Rhim H . Cho IH . Kim HC . Lee JI . Hwang SH . Nah SY . Ginseng Gintonin Contains Ligands for GPR40 and GPR55 . 10.3390/molecules25051102 . Molecules . 25 . 5 . 1102 . 2020 . 32121640 . 7179172 . free .
• Nam SM . Choi SH . Cho HJ . Seo JS . Choi M . Nahm SS . Chang BJ . Nah SY . Ginseng Gintonin Attenuates Lead-Induced Rat Cerebellar Impairments During Gestation and Lactation . 10.3390/biom10030385 . Biomolecules . 10 . 3 . 385 . 2020 . 32131481 . 7175158 . free .
• Rahman MA . Hwang H . Nah SY . Rhim H . Gintonin Stimulates Autophagic Flux in Primary Cortical Astrocytes . 10.1016/j.jgr.2018.08.004 . J Ginseng Res . 44 . 1 . 67–78 . 2020 . 32148391 . 7033340 . free .

Notes and References

1. Pyo . M. K. . Choi . S. H. . Hwang . S. H. . Shin . T. J. . Lee . B. H. . Lee . S. M. . Lim . Y. H. . Kim . D. H. . Nah . S. Y. . Novel Glycolipoproteins from Ginseng . 10.5142/jgr.2011.35.1.092 . Journal of Ginseng Research . 35 . 92–103 . 2011 . free .
2. Hwang . S. H. . Shin . T. J. . Choi . S. H. . Cho . H. J. . Lee . B. H. . Pyo . M. K. . Lee . J. H. . Kang . J. . Kim . H. J. . Park . C. W. . Shin . H. C. . Nah . S. Y. . 10.1007/s10059-012-2216-z . Gintonin, newly identified compounds from ginseng, is novel lysophosphatidic acids-protein complexes and activates G protein-coupled lysophosphatidic acid receptors with high affinity . Molecules and Cells . 33 . 2 . 151–162 . 2012 . 22286231. 3887723.
3. Choi . SH . Hong . MK . Kim . HJ . Ryoo . N . Rhim . H . Nah . SY . Kang . LW . 2015 . Structure of ginseng major latex-like protein 151 and its proposed lysophosphatidic acid-binding mechanism . Acta Crystallographica Section D . 71 . pt5 . 1039–50 . 25945569 . 10.1107/S139900471500259X .
4. 10.3233/JAD-2012-120439. 22543851. Gintonin, a ginseng-derived lysophosphatidic acid receptor ligand, attenuates Alzheimer's disease-related neuropathies: involvement of non-amyloidogenic processing. Journal of Alzheimer's Disease. 31. 1. 207–223. 2012. Hwang SH. Shin EJ, Shin TJ, Lee BH, Choi SH, Kang J, Kim HJ, Kwon SH, Jang CG, Lee JH, Kim HC, Nah SY.
5. Kim . HJ . Shin . EJ . Lee . BH . Choi . SH . Jung . SW . Cho . IH . Hwang . SH . Kim . JY . Han . JS . Chung . C . Jang . CG . Rhim . H . Kim . HC . Nah . SY . 2015 . Oral Administration of Gintonin Attenuates Cholinergic Impairments by Scopolamine, Amyloid-β Protein, and Mouse Model of Alzheimer's Disease . Molecules and Cells . 38. 9. 796–805. 26255830 . 10.14348/molcells.2015.0116 . 4588723.
6. 10.1097/WAD.0000000000000213 . 29028648. Gintonin Administration is Safe and Potentially Beneficial in Cognitively Impaired Elderly. Alzheimer Dis Assoc Disord . 32. 85–87. 2017. Moon J. Choi SH, Shim JY, Park HJ, Oh MJ, Kim M, Nah SY.. 1 .
7. 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 . 10.1016/j.neuint.2016.10.006 . Neurochemistry International . 101 . 56–65 . 2016 . 27765516.
8. 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 . 10.1016/j.jad.2017.03.026 . J Affect Disord . 215 . 23–29 . 2017 . 28314177 .
9. Lee. BH . Kim . HK . Jang . M . Kim . HJ . Choi . SH . Hwang . SH . Kim . HC . Rhim . H . Choi . IH . Nah . SY . Effects of Gintonin-Enriched Fraction in an Atopic Dermatitis Animal Model: Involvement of Autotaxin Regulation . 10.1248/bpb.b17-00124 . Biol Pharm Bull . 40. 7 . 1063–1070 . 2017 . 28674249 . free .
10. 10.3892/ijo.2012.1709. 23174888. Suppression of metastasis of intravenously-inoculated B16/F10 melanoma cells by the novel ginseng-derived ingredient, gintonin: Involvement of autotaxin inhibition. International Journal of Oncology. 42. 1. 317–326. 2012. Hwang SH. Lee BH, Kim HJ, Cho HJ, Shin HC, Im KS, Choi SH, Shin TJ, Lee SM, Nam SW, Kim HC, Rhim H, Nah SY.. free.