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.[1]
Gintonin is a glycolipoproteinfraction 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.[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.[4]
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.[4]
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.[5][6] Oral gintonin is well-tolerated by human AD patients in a small study, but the benefits are unclear.[7]
A number of other effects are attributed to oral administration of gintonin-enriched extract in rodents.[8][9][10][11]
^ abChoi, 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. PMID25945569.
^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. PMID22543851.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^Moon J, Choi SH, Shim JY, Park HJ, Oh MJ, Kim M, Nah SY. (2017). "Gintonin Administration is Safe and Potentially Beneficial in Cognitively Impaired Elderly". Alzheimer Dis Assoc Disord. 32 (1): 85–87. doi:10.1097/WAD.0000000000000213. PMID29028648.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^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. PMID27765516.
^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. PMID28314177.
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. PMID22543851.{{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. PMID23017203.
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. PMID23769686.
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. PMID25445364.
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. PMID25505112.
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. PMID25945569.
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. PMID26191656.
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. PMID27765516.
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. PMID29028648.
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. PMID29604355.
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. PMID30117105.
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 Functionss". Gerontology. 64 (6): 562–575. doi:10.1159/000491113. PMID30138913.
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. PMID29675576.
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. PMID29870296.
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. PMID30853569.
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