Gintonin

Recognition of lysophosphatidic acid C18:2 by ginseng major latex-like protein 151. (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.^[1]

Gintonin is a glycolipoprotein fraction isolated from 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.^[2][3]

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 and deliver LPA to its cognate receptors to elicit cellular effects such as [Ca²⁺]i transient and morphological changes.^[4]

Lysophospholipid receptors are the high affinity and selective target receptor of gintonin. Gintonin induces [Ca²⁺]i transient in animal cells. Gintonin also shows in vivo anti-Alzheimer's disease through LPA receptor-mediated non-amyloidogenic pathway ^[5] and boosting of hippocampal cholinergic system ^[6] and in vivo anti-metastatic effect by inhibition of autotaxin activity.^[7]

See also

• Ginseng
• Ginsenoside
• Lysophosphatidic acid
• Lysophospholipid receptor

References

1. 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 Biological Crystallography 71 (pt5): 1039–50. doi:10.1107/S139900471500259X. PMID 25945569.
2. 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.
3. 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.
4. 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 Biological Crystallography 71 (pt5): 1039–50. doi:10.1107/S139900471500259X. PMID 25945569.
5. 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. doi:10.3233/JAD-2012-120439.
6. 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: 796–805. doi:10.14348/molcells.2015.0116. PMID 26255830.
7. 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. (2012). "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. doi:10.3892/ijo.2012.1709.

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. doi:10.3233/JAD-2012-120439.
• 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. 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.
• 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. 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: 656–63. doi:10.14348/molcells.2014.0087. PMID 25234465.
• 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 Biological Crystallography 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: 796–805. doi:10.14348/molcells.2015.0116. 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.
• 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: 398–405. doi:10.1016/j.jgr.2015.05.002.