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 and alleviates cognitive functions in elderly human Alzheimer's disease patients ^[5][6] and boosting of hippocampal cholinergic system,^[7] hippocampal neurogenesis,^[8] anti-depression ^[9] and in vivo anti-metastatic and anti-atopic dermatitis effects^[10] by inhibition of autotaxin activity.^[11]

See also

• Ginseng
• Ginsenoside
• Lysophosphatidic acid
• Lysophospholipid receptor

References

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. 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.
• 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: 656–63. doi:10.14348/molcells.2014.0087. PMC 4179134. 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. 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. 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.
• 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.
• 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.
• 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: 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.