Gintonin

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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]

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References[edit]

  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. 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. 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. ^ 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. doi:10.1097/WAD.0000000000000213.
  7. ^ 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.
  8. ^ 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.
  9. ^ 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.
  10. ^ 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.
  11. ^ 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.

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