Gintonin

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.

Major latex-like protein
Gintonin bound to lysophosphatidic acid C18:2. (a) Superposition of ginseng major latex-like protein 151 (GLP;green) and the lowest energy major latex protein 28 conformer (yellow). The mutated residues in GLP are represented by red sticks. (b) The electrostatic molecular surface of GLP modelled with LPA C18:2 in close conformation. The positions of the residues that recognize LPA C18:2 are labelled.
Identifiers
Organism	Panax ginseng
Symbol	mlp151
UniProt	B5THI3
Search for Structures Swiss-model Domains InterPro

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.

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.

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. Oral gintonin is well-tolerated by human AD patients in a small study, but the benefits are unclear.

A number of other effects are attributed to oral administration of gintonin-enriched extract in rodents.

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. (2011). "Novel Glycolipoproteins from Ginseng". Journal of Ginseng Research. 35: 92–103. doi:10.5142/jgr.2011.35.1.092.
• 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. (2011). "A Simple Method for the Preparation of Crude Gintonin from Ginseng Root, Stem, and Leaf". Journal of Ginseng Research. 35 (2): 209–218. doi:10.5142/jgr.2011.35.2.209. PMC 3659522. PMID 23717063.
• Choi, S. H.; Shin, T. J.; Lee, B. H.; Hwang, S. H.; Kang, J. Y.; Kim, H. J.; Park, C. W.; Nah, S. Y. (2011). "An Edible Gintonin Preparation from Ginseng". Journal of Ginseng Research. 35 (4): 471–478. doi:10.5142/jgr.2011.35.4.471. PMC 3659555. PMID 23717094.
• 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. (2012). "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. doi:10.1007/s10059-012-2216-z. PMC 3887723. PMID 22286231.
• Hwang SH, Shin EJ, Shin TJ, Lee BH, Choi SH, Kang J, Kim HJ, Kwon SH, Jang CG, Lee JH, Kim HC, Nah SY (2012). "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. doi:10.3233/JAD-2012-120439. PMID 22543851.{{cite journal}}: CS1 maint: multiple names: authors list (link)
• Nah, S. Y. (2012). "Gintonin: A novel ginseng-derived ligand that _targets G protein- coupled lysophosphatidic acid receptors". Current Drug _targets. 13 (13): 1659–64. doi:10.2174/138945012803529947. PMID 23017203.
• 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. (2012). "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. doi:10.1007/s10059-012-0254-4. PMC 3887827. PMID 23161173.
• 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. (2013). "Gintonin, a ginseng-derived lysophosphatidic acid receptor ligand, potentiates ATP-gated P2X1 receptor channel currents". Molecules and Cells. 35 (2): 142–50. doi:10.1007/s10059-013-2293-x. PMC 3887903. PMID 23456336.
• Choi, S. H.; Lee, B. H.; Hwang, S. H.; Kim, H. J.; Lee, S. M.; Kim, H. C.; Rhim, H. W.; Nah, S. Y. (2013). "Molecular Mechanisms of Large-Conductance Ca2+-Activated Potassium Channel Activation by Ginseng Gintonin". Evidence-Based Complementary and Alternative Medicine. 2013: 1–14. doi:10.1155/2013/323709. PMC 3638619. PMID 23662129.
• Lee, J. H.; Choi, S. H.; Lee, B. H.; Hwang, S. H.; Kim, H. J.; Rhee, J.; Chung, C.; Nah, S. Y. (2013). "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. doi:10.1016/j.neulet.2013.05.048. PMID 23769686.
• Im, D. S.; Nah, S. Y. (2013). "Yin and Yang of ginseng pharmacology: Ginsenosides vs gintonin". Acta Pharmacologica Sinica. 34 (11): 1367–73. doi:10.1038/aps.2013.100. PMC 3818586. PMID 24122014.
• 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. (2014). "Characteristics of Gintonin-Mediated Membrane Depolarization of Pacemaker Activity in Cultured Interstitial Cells of Cajal". Cellular Physiology and Biochemistry. 34 (3): 873–90. doi:10.1159/000366306. PMID 25199952.
• 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 (2014). "Ginseng Gintonin Activates the Human Cardiac Delayed Rectifier K+ Channel: Involvement of Ca2+/Calmodulin Binding Sites". Molecules and Cells. 37 (9): 656–63. doi:10.14348/molcells.2014.0087. PMC 4179134. PMID 25234465.{{cite journal}}: CS1 maint: multiple names: authors list (link)
• 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. doi:10.1016/j.neulet.2014.11.007. PMID 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. doi:10.1152/jn.00667.2014. PMID 25505112.
• 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. doi:10.1107/S139900471500259X. PMID 25945569.
• 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. doi:10.1016/j.neulet.2015.07.012. PMID 26191656.
• 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. doi:10.14348/molcells.2015.0116. PMC 4588723. PMID 26255830.
• 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. doi:10.1248/bpb.b15-00171. PMID 26424022.
• 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. doi:10.1016/j.jgr.2015.05.002. PMC 4593782. PMID 26869834.
• Kim, HJ; Kim, DJ; Shin, EJ; Lee, BH; Choi, SH; Hwang, SH; Rhim, H; Cho, IH; Kim, HC; Nah, SY (2016). "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". Neurochemistry International. 101: 56–65. doi:10.1016/j.neuint.2016.10.006. PMID 27765516.
• Hwang, SH; Lee, BH; Choi, SH; Kim, HJ; Won, KJ; Lee, HM; Rhim, H; Kim, HC; Nah, SY (2016). "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". Journal of Ginseng Research. 40 (4): 325–333. doi:10.1016/j.jgr.2015.10.002. PMC 5052429. PMID 27746684.
• Nah, SY; Kim, KH; Choi, MS; Ha, KS; Lim, DY (2016). "Gintonin facilitates catecholamine secretion from the perfused adrenal medulla". Korean J Physiol Pharmacol. 20 (6): 629–639. doi:10.4196/kjpp.2016.20.6.629. PMC 5106397. PMID 27847440.
• Kim, HJ; Park, SD; Lee, RM; Lee, BH; Choi, SH; Hwang, SH; Rhim, H; Kim, HC; Nah, SY (2017). "Gintonin attenuates depressive-like behaviors associated with alcohol withdrawal in mice". J Affect Disord. 215: 23–29. doi:10.1016/j.jad.2017.03.026. PMID 28314177.
• Lee, BH; Kim, HK; Jang, M; Kim, HJ; Choi, SH; Hwang, SH; Kim, HC; Rhim, H; Choi, IH; Nah, SY (2017). "Effects of Gintonin-Enriched Fraction in an Atopic Dermatitis Animal Model: Involvement of Autotaxin Regulation". Biol Pharm Bull. 40 (7): 1063–1070. doi:10.1248/bpb.b17-00124. PMID 28674249.
• Lee BH; Kim HK; Jang M; Kim HJ; Choi SH; Hwang SH; Kim HC; Rhim H; Cho IH; Nah SY (2017). "Effects of Gintonin-Enriched Fraction in an Atopic Dermatitis Animal Model: Involvement of Autotaxin Regulation". Biological and Pharmaceutical Bulletin. 40 (7): 1063–70. doi:10.1248/bpb.b17-00124. PMID 28674249.
• Moon J; Choi SH; Shim JY; Park HJ; Oh MJ; Kim M; Nah SY (2018). "EGintonin Administration Is Safe and Potentially Beneficial in Cognitively Impaired Elderly". Alzheimer Dis Assoc Disord. 32 (1): 85–87. doi:10.1097/WAD.0000000000000213. PMID 29028648.
• Lee BH; Choi SH; Kim HJ; Park SD; Rhim H; Kim HC; Hwang SH; Nah SY (2018). "Gintonin Absorption in Intestinal Model Systems". J Ginseng Res. 42 (1): 35–41. doi:10.1016/j.jgr.2016.12.007. PMC 5766688. PMID 29348720.
• Kim DG; Jang M; Choi SH; Kim HJ; Jhun H; Kim HC; Rhim H; Cho IH; Nah SY (2018). "Gintonin, a Ginseng-Derived Exogenous Lysophosphatidic Acid Receptor Ligand, Enhances Blood-Brain Barrier Permeability and Brain Delivery". Int J Biol Macromol. 114: 1325–1337. doi:10.1016/j.ijbiomac.2018.03.158. PMID 29604355.
• Choi JH; Jang M; Oh S; Nah SY; Cho IH (2018). "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". Front Pharmacol. 9: 515. doi:10.3389/fphar.2018.00515. PMC 5974039. PMID 29875659.
• Choi SH; Kim HJ; Cho HJ; Park SD; Lee NE; Hwang SH; Cho IH; Hwang H; Rhim H; Kim HC; Nah SY (2019). "Gintonin, a Ginseng-Derived Exogenous Lysophosphatidic Acid Receptor Ligand, Protects Astrocytes From Hypoxic and Re-oxygenation Stresses Through Stimulation of Astrocytic Glycogenolysis". Mol Neurobiol. 56 (5): 3280–3294. doi:10.1007/s12035-018-1308-1. PMID 30117105.
• Nam SM; Hwang H; Seo M; Chang BJ; Kim HJ; Choi SH; Rhim H; Kim HC; Cho IH; Nah SY (2018). "Gintonin Attenuates D-Galactose-Induced Hippocampal Senescence by Improving Long-Term Hippocampal Potentiation, Neurogenesis, and Cognitive Functions". Gerontology. 64 (6): 562–575. doi:10.1159/000491113. PMID 30138913.
• Kim HJ; Jung SW; Kim SY; Cho IH; Kim HC; Rhim H; Kim M; Nah SY (2018). "Panax Ginseng as an Adjuvant Treatment for Alzheimer's Disease". J Ginseng Res. 42 (4): 401–411. doi:10.1016/j.jgr.2017.12.008. PMC 6190533. PMID 30337800.
• Jo MG; Ikram M; Jo MH; Yoo L; Chung KC; Nah SY; Hwang H; Rhim H; Kim MO; Nah SY (2019). "Gintonin Mitigates MPTP-Induced Loss of Nigrostriatal Dopaminergic Neurons and Accumulation of α-Synuclein via the Nrf2/HO-1 Pathway". Mol Neurobiol. 56 (1): 39–55. doi:10.1007/s12035-018-1020-1. PMID 29675576.
• Irfan M; Jeong D; Saba E; Kwon HW; Shin JH; Jeon BR; Kim S; Kim SD; Lee DH; Nah SY; Rhee MH (2019). "Gintonin Modulates Platelet Function and Inhibits Thrombus Formation via Impaired Glycoprotein VI Signaling". Platelets. 30 (5): 589–598. doi:10.1080/09537104.2018.1479033. PMID 29870296.
• Jang M; Choi JH; Chang Y; Lee SJ; Nah SY; Cho IH (2019). "Gintonin, a Ginseng-Derived Ingredient, as a Novel Therapeutic Strategy for Huntington's Disease: Activation of the Nrf2 Pathway Through Lysophosphatidic Acid Receptors". Brain Behav Immun. 80: 146–162. doi:10.1016/j.bbi.2019.03.001. PMID 30853569.
• Cho HJ; Choi SH; Kim HJ; Lee BH; Rhim H; Kim HC; Hwang SH; Nah SY (2019). "Bioactive Lipids in Gintonin-Enriched Fraction From Ginseng". J Ginseng Res. 43 (2): 209–217. doi:10.1016/j.jgr.2017.11.006. PMC 6437394. PMID 30962735.
• Choi SH; Kim HJ; Cho HJ; Park SD; Lee NE; Hwang SH; Rhim H; Kim HC; Cho IH; Nah SY (2019). "Gintonin-mediated Release of Astrocytic Vascular Endothelial Growth Factor Protects Cortical Astrocytes From Hypoxia-Induced Cell Damages". J Ginseng Res. 43 (2): 305–311. doi:10.1016/j.jgr.2018.05.006. PMC 6437663. PMID 30976168.
• Mijan MA; Kim JY; Moon SY; Choi SH; Nah SY; Yang HJ (2019). "Gintonin Enhances Proliferation, Late Stage Differentiation, and Cell Survival From Endoplasmic Reticulum Stress of Oligodendrocyte Lineage Cells". Front Pharmacol. 10: 1211. doi:10.3389/fphar.2019.01211. PMC 6797839. PMID 31680979.
• Lee R; Lee NE; Hwang H; Rhim H; Cho IH; Nah SY (2019). "Ginseng Gintonin Enhances Hyaluronic Acid and Collagen Release From Human Dermal Fibroblasts Through Lysophosphatidic Acid Receptor Interaction". Molecules. 24 (24): 4438. doi:10.3390/molecules24244438. PMC 6943507. PMID 31817172.
• Kim HJ; Choi SH; Lee NE; Cho HJ; Rhim H; Kim HC; Hwang SH; Nah SY (2020). "Effects of Gintonin-Enriched Fraction on Methylmercury-Induced Neurotoxicity and Organ Methylmercury Elimination". Int J Environ Res Public Health. 17 (3): 838. doi:10.3390/ijerph17030838. PMC 7038146. PMID 32013120.
• Lee NE; Park SD; Hwang H; Choi SH; Lee RM; Nam SM; Choi JH; Rhim H; Cho IH; Kim HC; Hwang SH; Nah SY (2020). "Effects of a Gintonin-Enriched Fraction on Hair Growth: An in vitro and in vivo Study". J Ginseng Res. 44 (1): 168–177. doi:10.1016/j.jgr.2019.05.013. PMC 7033365. PMID 32095099.
• Chei S; Song JH; Oh HJ; Lee K; Jin H; Choi SH; Nah SY; Lee BY (2020). "Gintonin-Enriched Fraction Suppresses Heat Stress-Induced Inflammation Through LPA Recepto". Molecules. 25 (5): 1019. doi:10.3390/molecules25051019. PMC 7179209. PMID 32106493.
• Cho YJ; Choi SH; Lee R; Hwang H; Rhim H; Cho IH; Kim HC; Lee JI; Hwang SH; Nah SY (2020). "Ginseng Gintonin Contains Ligands for GPR40 and GPR55". Molecules. 25 (5): 1102. doi:10.3390/molecules25051102. PMC 7179172. PMID 32121640.
• Nam SM; Choi SH; Cho HJ; Seo JS; Choi M; Nahm SS; Chang BJ; Nah SY (2020). "Ginseng Gintonin Attenuates Lead-Induced Rat Cerebellar Impairments During Gestation and Lactation". Biomolecules. 10 (3): 385. doi:10.3390/biom10030385. PMC 7175158. PMID 32131481.
• Rahman MA; Hwang H; Nah SY; Rhim H (2020). "Gintonin Stimulates Autophagic Flux in Primary Cortical Astrocytes". J Ginseng Res. 44 (1): 67–78. doi:10.1016/j.jgr.2018.08.004. PMC 7033340. PMID 32148391.