Ginseng berry aqueous extract prevents scopolamine‑induced memory impairment in mice

Hu,Jin  Ryul; Chun,Yoon  Seok; Kim,Jong  Kyu; Cho,Il  Je; Ku,Sae  Kwang

doi:10.3892/etm.2019.8090

Ginseng berry aqueous extract prevents scopolamine‑induced memory impairment in mice

Authors:
- Jin Ryul Hu
- Yoon Seok Chun
- Jong Kyu Kim
- Il Je Cho
- Sae Kwang Ku
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Affiliations: Research Center for Herbal Convergence on Liver Disease, College of Korean Medicine, Daegu Haany University, Gyeongsan, Gyeongsangbuk‑do 38610, Republic of Korea, Central Research Center, Aribio Co., Ltd., Pyeongtaek, Gyeonggi‑do 17749, Republic of Korea
Published online on: October 8, 2019 https://doi.org/10.3892/etm.2019.8090
Pages: 4388-4396
Copyright: © Hu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ginseng berry exhibits a diverse range of pharmacological activities. The present study aimed to examine the neuroprotective effects of ginseng berry aqueous extract (GBE) against oxidative stress and to assess the impact of GBE on memory impairment in mice. In HT‑22 cells, GBE pretreatment significantly inhibited glutamate‑ and hydrogen peroxide‑mediated cytotoxicity in a concentration‑dependent manner, while treatment with up to 100 µg/ml GBE alone did not change cell viability. In a murine model of scopolamine (SCP)‑induced memory impairment, results from the passive avoidance test and the Morris water maze test indicated that GBE administration for 4 weeks prolonged step‑through latency time and shortened escape latency time, suggesting that GBE can attenuate deficits in long‑term memory induced by SCP. Additionally, GBE prevented SCP‑induced reductions in acetylcholine by decreasing acetylcholinesterase activity and upregulating choline acetyltransferase mRNA levels in the hippocampus. GBE mitigated SCP‑mediated mRNA decreases in brain‑derived neurotrophic factor levels and its associated signaling molecules. Furthermore, GBE administration significantly suppressed malondialdehyde production and increased glutathione levels, catalase activity and superoxide dismutase activity in SCP‑induced memory impaired mice. Therefore, the results of the current study indicated that ginseng berry may be a potential candidate for treating or preventing memory deficits that are associated with neurodegenerative disorders.

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1	Burns A and Iliffe S: Alzheimer's disease. BMJ. 338:b1582009. View Article : Google Scholar : PubMed/NCBI
2	Golde TE: Disease modifying therapy for AD? J Neurochem. 99:689–707. 2006. View Article : Google Scholar : PubMed/NCBI
3	Francis PT, Palmer AM, Snape M and Wilcock GK: The cholinergic hypothesis of Alzheimer's disease: A review of progress. J Neurol Neurosurg Psychiatry. 66:137–147. 1999. View Article : Google Scholar : PubMed/NCBI
4	Ibach B and Haen E: Acetylcholinesterase inhibition in Alzheimer's Disease. Curr Pharm Des. 10:231–251. 2004. View Article : Google Scholar : PubMed/NCBI
5	Rountree SD, Chan W, Pavlik VN, Darby EJ, Siddiqui S and Doody RS: Persistent treatment with cholinesterase inhibitors and/or memantine slows clinical progression of Alzheimer disease. Alzheimers Res Ther. 1:72009. View Article : Google Scholar : PubMed/NCBI
6	Kim CK, Cho DH, Lee KS, Lee DK, Park CW, Kim WG, Lee SJ, Ha KS, Goo Taeg O, Kwon YG and Kim YM: Ginseng berry extract prevents atherogenesis via anti-inflammatory action by upregulating phase II gene expression. Evid Based Complement Alternat Med. 2012:4903012012. View Article : Google Scholar : PubMed/NCBI
7	Kim YK, Yoo DS, Xu H, Park NI, Kim HH, Choi JE and Park SU: Ginsenoside content of berries and roots of three typical Korean ginseng (Panax ginseng) cultivars. Nat Prod Commun. 4:903–906. 2009.PubMed/NCBI
8	In-Ho C, Byung-Woo K, Yun-Jae P, Han-Joo L, Sok P and Namju L: Ginseng berry extract increases nitric oxide level in vascular endothelial cells and improves cGMP expression and blood circulation in muscle cells. J Exerc Nutrition Biochem. 22:6–13. 2018. View Article : Google Scholar : PubMed/NCBI
9	Dey L, Xie JT, Wang A, Wu J, Maleckar SA and Yuan CS: Anti-hyperglycemic effects of ginseng: Comparison between root and berry. Phytomedicine. 10:600–605. 2003. View Article : Google Scholar : PubMed/NCBI
10	Seo E, Kim S, Lee SJ, Oh BC and Jun HS: Ginseng berry extract supplementation improves age-related decline of insulin signaling in mice. Nutrients. 7:3038–3053. 2015. View Article : Google Scholar : PubMed/NCBI
11	Yang SO, Park HR, Sohn ES, Lee SW, Kim HD, Kim YC, Kim KH, Na SW, Choi HK, Arasu MV and Kim YO: Classification of ginseng berry (Panax ginseng C.A. MEYER) extract using 1H NMR spectroscopy and its inhibition of lipid accumulation in 3T3-L1 cells. BMC Complement Altern Med. 14:4552014. View Article : Google Scholar : PubMed/NCBI
12	Kim MH, Lee J, Jung S, Kim JW, Shin JH and Lee HJ: The involvement of ginseng berry extract in blood flow via regulation of blood coagulation in rats fed a high-fat diet. J Ginseng Res. 41:120–126. 2017. View Article : Google Scholar : PubMed/NCBI
13	Ma ZN, Liu Z, Wang Z, Ren S, Tang S, Wang YP, Xiao SY, Chen C and Li W: Supplementation of American ginseng berry extract mitigated cisplatin-evoked nephrotoxicity by suppressing ROS-mediated activation of MAPK and NF-κB signaling pathways. Food Chem Toxicol. 110:62–73. 2017. View Article : Google Scholar : PubMed/NCBI
14	Xu XY, Wang Z, Ren S, Leng J, Hu JN, Liu Z, Chen C and Li W: Improved protective effects of American ginseng berry against acetaminophen-induced liver toxicity through TNF-α-mediated caspase-3/-8/-9 signaling pathways. Phytomedicine. 51:128–138. 2018. View Article : Google Scholar : PubMed/NCBI
15	Zhang W, Xu L, Cho SY, Min KJ, Oda T, Zhang L, Yu Q and Jin JO: Ginseng berry extract attenuates dextran sodium sulfate-induced acute and chronic colitis. Nutrients. 8:1992016. View Article : Google Scholar : PubMed/NCBI
16	Seo JY, Ju SH, Oh J, Lee SK and Kim JS: Neuroprotective and cognition-enhancing effects of compound K isolated from red ginseng. J Agric Food Chem. 64:2855–2864. 2016. View Article : Google Scholar : PubMed/NCBI
17	Maurice T, Lockhart BP and Privat A: Amnesia induced in mice by centrally administered beta-amyloid peptides involves cholinergic dysfunction. Brain Res. 706:181–193. 1996. View Article : Google Scholar : PubMed/NCBI
18	Kim J, Kim SH, Lee DS, Lee DJ, Kim SH, Chung S and Yang HO: Effects of fermented ginseng on memory impairment and β-amyloid reduction in Alzheimer's disease experimental models. J Ginseng Res. 37:100–107. 2013. View Article : Google Scholar : PubMed/NCBI
19	Morris R: Development of a water maze procedure for studying spatial learning in the rat. J Neurosci Methods. 11:47–60. 1984. View Article : Google Scholar : PubMed/NCBI
20	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
21	Lee JW, Choi BR, Kim YC, Choi DJ, Lee YS, Kim GS, Baek NI, Kim SY and Lee DY: Comprehensive profiling and quantification of ginsenosides in the root, stem, leaf, and berry of Panax ginseng by UPLC-QTOF/MS. Molecules. 22:E21472017. View Article : Google Scholar : PubMed/NCBI
22	Nakajo Y, Miyamoto S, Nakano Y, Xue JH, Hori T and Yanamoto H: Genetic increase in brain-derived neurotrophic factor levels enhances learning and memory. Brain Res. 1241:103–109. 2008. View Article : Google Scholar : PubMed/NCBI
23	Cunha C, Brambilla R and Thomas KL: A simple role for BDNF in learning and memory? Front Mol Neurosci. 3:12010.PubMed/NCBI
24	Martin SJ, Grimwood PD and Morris RG: Synaptic plasticity and memory: An evaluation of the hypothesis. Annu Rev Neurosci. 23:649–711. 2000. View Article : Google Scholar : PubMed/NCBI
25	Yang Q, Lin J, Zhang H, Liu Y, Kan M, Xiu Z, Chen X, Lan X, Li X, Shi X, et al: Ginsenoside compound K regulates amyloid β via the Nrf2/Keap1 signaling pathway in mice with scopolamine hydrobromide-induced memory impairments. J Mol Neurosci. 67:62–71. 2019.PubMed/NCBI
26	Lu C, Lv J, Dong L, Jiang N, Wang Y, Wang Q, Li Y, Chen S, Fan B, Wang F and Liu X: Neuroprotective effects of 20(S)-protopanaxatriol (PPT) on scopolamine-induced cognitive deficits in mice. Phytother Res. 32:1056–1063. 2018. View Article : Google Scholar : PubMed/NCBI
27	Kim J, Shim J, Lee S, Cho WH, Hong E, Lee JH, Han JS, Lee HJ and Lee KW: Rg3-enriched ginseng extract ameliorates scopolamine-induced learning deficits in mice. BMC Complement Altern Med. 16:662016. View Article : Google Scholar : PubMed/NCBI
28	Xu T, Shen X, Yu H, Sun L, Lin W and Zhang C: Water-soluble ginseng oligosaccharides protect against scopolamine-induced cognitive impairment by functioning as an antineuroinflammatory agent. J Ginseng Res. 40:211–219. 2016. View Article : Google Scholar : PubMed/NCBI
29	Peña ID, Yoon SY, Kim HJ, Park S, Hong EY, Ryu JH, Park IH and Cheong JH: Effects of ginseol k-g3, an Rg3-enriched fraction, on scopolamine-induced memory impairment and learning deficit in mice. J Ginseng Res. 38:1–7. 2014. View Article : Google Scholar : PubMed/NCBI
30	Jin SH, Park JK, Nam KY, Park SN and Jung NP: Korean red ginseng saponins with low ratios of protopanaxadiol and protopanaxatriol saponin improve scopolamine-induced learning disability and spatial working memory in mice. J Ethnopharmacol. 66:123–129. 1999. View Article : Google Scholar : PubMed/NCBI
31	Li J, Liu Y, Li W, Wang Z, Guo P, Li L and Li N: Metabolic profiling of the effects of ginsenoside Re in an Alzheimer's disease mouse model. Behav Brain Res. 337:160–172. 2018. View Article : Google Scholar : PubMed/NCBI
32	Chen F, Eckman EA and Eckman CB: Reductions in levels of the Alzheimer's amyloid beta peptide after oral administration of ginsenosides. FASEB J. 20:1269–1271. 2006. View Article : Google Scholar : PubMed/NCBI
33	Du Y, Fu M, Wang YT and Dong Z: Neuroprotective effects of ginsenoside Rf on amyloid-β-induced neurotoxicity in vitro and in vivo. J Alzheimers Dis. 64:309–322. 2018. View Article : Google Scholar : PubMed/NCBI
34	Liu JF, Yan XD, Qi LS, Li L, Hu GY, Li P and Zhao G: Ginsenoside Rd attenuates Aβ25-35-induced oxidative stress and apoptosis in primary cultured hippocampal neurons. Chem Biol Interact. 239:12–18. 2015. View Article : Google Scholar : PubMed/NCBI
35	Wang Q, Sun LH, Jia W, Liu XM, Dang HX, Mai WL, Wang N, Steinmetz A, Wang YQ and Xu CJ: Comparison of ginsenosides Rg1 and Rb1 for their effects on improving scopolamine-induced learning and memory impairment in mice. Phytother Res. 24:1748–1754. 2010. View Article : Google Scholar : PubMed/NCBI
36	Klinkenberg I and Blokland A: The validity of scopolamine as a pharmacological model for cognitive impairment: A review of animal behavioral studies. Neurosci Biobehav Rev. 34:1307–1350. 2010. View Article : Google Scholar : PubMed/NCBI
37	Lorenzini CA, Baldi E, Bucherelli C, Sacchetti B and Tassoni G: Role of dorsal hippocampus in acquisition, consolidation and retrieval of rat's passive avoidance response: A tetrodotoxin functional inactivation study. Brain Res. 730:32–39. 1996. View Article : Google Scholar : PubMed/NCBI
38	Barnes CA, Danysz W and Parsons CG: Effects of the uncompetitive NMDA receptor antagonist memantine on hippocampal long-term potentiation, short-term exploratory modulation and spatial memory in awake, freely moving rats. Eur J Neurosci. 8:565–571. 1996. View Article : Google Scholar : PubMed/NCBI
39	Madara JC and Levine ES: Presynaptic and postsynaptic NMDA receptors mediate distinct effects of brain-derived neurotrophic factor on synaptic transmission. J Neurophysiol. 100:3175–3184. 2008. View Article : Google Scholar : PubMed/NCBI
40	Korte M, Carroll P, Wolf E, Brem G, Thoenen H and Bonhoeffer T: Hippocampal long-term potentiation is impaired in mice lacking brain-derived neurotrophic factor. Proc Natl Acad Sci USA. 92:8856–8860. 1995. View Article : Google Scholar : PubMed/NCBI
41	Segal RA: Selectivity in neurotrophin signaling: Theme and variations. Annu Rev Neurosci. 26:299–310. 2003. View Article : Google Scholar : PubMed/NCBI
42	Bozon B, Kelly A, Josselyn SA, Silva AJ, Davis S and Laroche S: MAPK, CREB and zif268 are all required for the consolidation of recognition memory. Philos Trans R Soc Lond B Biol Sci. 358:805–814. 2003. View Article : Google Scholar : PubMed/NCBI
43	Korte M, Kang H, Bonhoeffer T and Schuman E: A role of BDNF in the late-phase of hippocampal long-term potentiation. Neuropharmacology. 37:553–559. 1998. View Article : Google Scholar : PubMed/NCBI
44	Singh A, Kukreti R, Saso L and Kukreti S: Oxidative stress: A key modulator in neurodegenerative diseases. Molecules. 24:E15832019. View Article : Google Scholar : PubMed/NCBI
45	Olanow CW: An introduction to the free radical hypothesis in Parkinson's disease. Ann Neurol. 32 (Suppl):S2–S9. 1992. View Article : Google Scholar : PubMed/NCBI
46	Liu L, Vollmer MK, Ahmad AS, Fernandez VM, Kim H and Doré S: Pretreatment with Korean red ginseng or dimethyl fumarate attenuates reactive gliosis and confers sustained neuroprotection against cerebral hypoxic-ischemic damage by an Nrf2-dependent mechanism. Free Radic Biol Med. 131:98–114. 2019. View Article : Google Scholar : PubMed/NCBI
47	Sivandzade F, Prasad S, Bhalerao A and Cucullo L: NRF2 and NF-κB interplay in cerebrovascular and neurodegenerative disorders: Molecular mechanisms and possible therapeutic approaches. Redox Biol. 21:1010592019. View Article : Google Scholar : PubMed/NCBI
48	Lee MR, Yun BS, Park SY, Ly SY, Kim SN, Han BH and Sung CK: Anti-amnesic effect of Chong-Myung-Tang on scopolamine-induced memory impairments in mice. J Ethnopharmacol. 132:70–74. 2010. View Article : Google Scholar : PubMed/NCBI