Food Science and Biotechnology

, Volume 27, Issue 4, pp 1193–1200 | Cite as

Synergistic effect of Korean red ginseng and Pueraria montana var. lobata against trimethyltin-induced cognitive impairment

  • Young-Min Seo
  • Soo Jung Choi
  • Chan Kyu Park
  • Min Chul Gim
  • Dong-Hoon Shin


Many edible plant extracts exhibit biological activities. For example, the ethanol extract of Pueraria montana var. lobata (P. montana) inhibits acetylcholinesterase (AChE), and red ginseng is well known for promoting health. In this study the authors investigated the synergistic effect of P. montana and red ginseng extracts on AChE activity in vitro and in mouse brain tissues and trimethyltin (TMT)-induced cognitive impairment in a mouse model of TMT-induced neurodegeneration. A diet containing a mixture of P. montana and red ginseng extracts reversed learning and memory impairments in Y-maze and passive avoidance behavioral tests. In addition, the mixture inhibited AChE activity and lipid peroxidation synergistically.


Alzheimer’s disease Learning Memory Pueraria montana var. lobata Red ginseng 



This work was supported by a Korea University Grant.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.


  1. 1.
    Attele AS, Wu JA, Yuan CS. Ginseng pharmacology: multiple constituents and multiple actions. Biochem Pharmacol. 58: 1685–1693 (1999).CrossRefGoogle Scholar
  2. 2.
    Benishin CG, Lee R, Wang LC, Liu HJ. Effects of ginsenoside Rb1 on central cholinergic metabolism. Pharmacology. 42: 223–229 (1991).CrossRefGoogle Scholar
  3. 3.
    Benishin CG. Actions of ginsenoside Rb1 on choline uptake in central cholinergic nerve endings. Neurochem Int. 21: 1–5 (1992).CrossRefGoogle Scholar
  4. 4.
    Boissiere F, Faucheux B, Agid Y, Hirsch EC. Choline acetyltransferase mRNA expression in the striatal neurons of patients with Alzheimer’s disease. Neurosci. Lett. 225: 169–172 (1997).CrossRefGoogle Scholar
  5. 5.
    Cai RL, Li M, Xie SH, Song Y, Zou ZM, Zhu CY, Qi Y. Antihypertensive effect of total flavone extracts from Puerariae Radix. J. Ethnopharmacol. 133: 177–183 (2011).CrossRefGoogle Scholar
  6. 6.
    Cao X, Tian Y, Zhang T, Li X, Ito Y. Separation and purification of isoflavones from Pueraria lobata by high-speed counter-current chromatography. J. Chromatogr. 855: 709–713 (1999).CrossRefGoogle Scholar
  7. 7.
    Choi YH, Hong SS, Shin YS, Hwang BY, Park SY, Lee D. Phenolic compounds from Pueraria lobata protect PC12 cells against Abeta-induced toxicity. Arch. Pharm. Res. 33: 1651–1654 (2010).CrossRefGoogle Scholar
  8. 8.
    Choi SJ, Kim MJ, Heo HJ, Kim JK, Jun WJ, Kim HK, Kim EK, Kim MO, Cho HY, Hwang HJ, Kim YJ, Shin DH. Ameliorative effect of 1,2-benzenedicarboxylic acid dinonyl ester against amyloid β peptide-induced neurotoxicity. Amyloid. 16: 15–24 (2009).CrossRefGoogle Scholar
  9. 9.
    Choi SJ, Oh SS, Kim CR, Kwon YK, Suh SH, Kim JK, Park GG, Son SY, Shin DH. Perilla frutescens extract ameliorates acetylcholinesterase and trimethyltin chloride-induced neurotoxicity. J. Med. Food. 19: 281–289 (2016).CrossRefGoogle Scholar
  10. 10.
    Ellman GL, Courtney KD, Andres Jr V, Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol. 7: 88–95 (1961).CrossRefGoogle Scholar
  11. 11.
    Heo JH, Lee ST, Chu K, Oh M, Park HJ, Shim JY, Kim M. An open-label trial of Korean red ginseng as an adjuvant treatment for cognitive impairment in patients with Alzheimer’s disease. Eur. J. Neurol. 15:865–868 (2008).CrossRefGoogle Scholar
  12. 12.
    Heo HJ, Suh YM, Kim MJ, Choi SJ, Mun NS, Kim HK, Kim EK, Kim CJ, Cho HY, Kim YJ, Shin DH. Daidzein activates choline acetyltransferase from MC-IXC cells and improves drug-induced amnesia. Biosci. Biotechnol. Biochem. 70: 107–111 (2006).CrossRefGoogle Scholar
  13. 13.
    Hestrin S. The reaction of acetylcholine and other carboxylic acid derivatives with hydroxylamine, and its analytical application. J. Biol. Chem. 180: 249–261 (1949).Google Scholar
  14. 14.
    Hou Y, Yu YB, Liu G, Luo Y. A natural squamosamide derivative FLZ reduces amyloid-beta production by increasing non-amyloidogenic AbetaPP processing. J. Alzheimers Dis. 18: 153–165 (2009).CrossRefGoogle Scholar
  15. 15.
    Ikeya Y, Takeda S, Tunakawa M, Karakida H, Toda K, Yamaguchi T, Aburada M. Cognitive improving and cerebral protective effects of acylated oligosaccharides in Polygala tenuifolia. Biol. Pharm. Bull. 27: 1081–1085 (2004).CrossRefGoogle Scholar
  16. 16.
    Jin SH, Park JK, Nam KY, Park SN, 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).CrossRefGoogle Scholar
  17. 17.
    Kim JK, Choi SJ, Bae H, Kim CR, Cho HY, Kim YJ, Lim ST, Kim CJ, Kim HK, Sabrina P, Shin DH. Effects of methoxsalen from Poncirus trifoliata on acetylcholinesterase and trimethyltin-induced learning and memory impairment. Biosci. Biotechnol. Biochem. 75: 1984–1989 (2011).CrossRefGoogle Scholar
  18. 18.
    Kim CR, Choi SJ, Kwon YK, Kim JK, Kim YJ, Park GG, Shin DH. Cinnamomum loureirii extract inhibits acetylcholinesterase activity and ameliorates trimethyltin-induced cognitive dysfunction in mice. Biol. Pharm. Bull. 39: 1130–1136 (2016).CrossRefGoogle Scholar
  19. 19.
    Kim MJ, Choi SJ, Lim ST, Kim HK, Heo HJ, Kim EK, Jun WJ, Cho HY, Kim YJ, Shin DH. Ferulic acid supplementation prevents trimethyltin-induced cognitive deficits in mice. Biosci. Biotechnol. Biochem. 71:1063–1068 (2007).CrossRefGoogle Scholar
  20. 20.
    Kim HJ, Kim P, Shin CY. A comprehensive review of the therapeutic and pharmacological effects of ginseng and ginsenosides in central nervous system. J. Ginseng Res. 37:8–29 (2013).CrossRefGoogle Scholar
  21. 21.
    Liu X, Mo Y, Gong J, Li Z, Peng H, Chen J, Wang Q, Ke Z, Xie J. Puerarin ameliorates cognitive deficits in streptozotocin-induced diabetic rats. Metab. Brain Dis. 31: 417–423 (2016).CrossRefGoogle Scholar
  22. 22.
    Loullis CC, Dean RL, Lippa AS, Clody DE, Coupet J. Hippocampal muscarinic receptor loss following trimethyl tin administration. Pharmacol. Biochem. Behav. 22: 147–151 (1985).CrossRefGoogle Scholar
  23. 23.
    Ohno K, Tsujino A, Brengman JM, Happer CM, Bajzer Z, Udd B, Beyring R, Robb S, Kirkham FJ, Engel AG. Choline acetyltransferase mutations cause myasthenic syndrome associated with episodic apnea in humans. Proc. Natl. Acad. Sci. USA. 98: 2017–2022 (2001).CrossRefGoogle Scholar
  24. 24.
    Perry EK, Perry RH, Blessed G, Tomlinson BE. Changes in brain cholinesterases in senile dementia of Alzheimer type. Neuropathol. Appl. Neurobiol. 4: 273–277 (1978).CrossRefGoogle Scholar
  25. 25.
    Petkov VD, Mosharrof AH. Effects of standarized ginseng extract on learning, memory and physical capabilities. Am. J. Chin. Med. 15:19–29 (1987).CrossRefGoogle Scholar
  26. 26.
    Schliebs R, Arendt T. The cholinergic system in aging and neuronal degeneration. Behav. Brain Res. 221: 555–563 (2011).CrossRefGoogle Scholar
  27. 27.
    Shuto M, Higuchi K, Sugiyama C, Yoneyama M, Kuramoto N, Nagashima R, Kawada K, Ogita K. Endogenous and exogenous glucocorticoids prevent trimethyltin from causing neuronal degeneration of the mouse brain in vivo: involvement of oxidative stress pathways. J. Pharmacol. Sci. 110: 424–436 (2009).CrossRefGoogle Scholar
  28. 28.
    Terry AV, Buccafusco JJ. The cholinergic hypothesis of age and Alzheimer’s disease-related cognitive deficits: recent challenges and their implications for novel drug development. J. Pharmacol. Exp. Ther. 306: 821–827 (2003).CrossRefGoogle Scholar
  29. 29.
    Tsang D, Yeung HW, Tso WW, Peck H. Ginseng saponins: influence on neurotransmitter uptake in rat brain synaptosomes. Planta Med. 51: 221–224 (1985).CrossRefGoogle Scholar
  30. 30.
    Wang X, Cai J, Zhang J, Wang C, Yu A, Chen Y, Zuo Z. Acute trimethyltin exposure induces oxidative stress response and neuronal apoptosis in Sebastiscus marmoratus. Aquat. Toxicol. 90: 58–64 (2008).CrossRefGoogle Scholar
  31. 31.
    Wang Q, Sun LH, Jia W, Liu XM, Dang HX, Mai WL, Wang N, Steinmetz A, Wang YQ, 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).CrossRefGoogle Scholar
  32. 32.
    Woodruff ML, Baisden RH. Exposure to trimethyltin significantly enhances acetylcholinesterase staining in the rat dentate gyrus. Neurotoxicol. Teratol. 12:33–39 (1990).CrossRefGoogle Scholar
  33. 33.
    Yamaguchi Y, Haruta K, Kobayashi H. Effects of ginsenosides on impaired performance induced in the rat by scopolamine in a radial-arm maze. Psychoneuroendocrinology. 20: 645–653 (1995).CrossRefGoogle Scholar
  34. 34.
    Younkin SG, Goodridge B, Katz J, Lockett G, Nafziger D, Usiak MF. Molecular forms of acetylcholinesterases in Alzheimer’s disease. Fed. Proc. 45: 2982–2988 (1986).Google Scholar
  35. 35.
    Zhang Z, Lam TN, Zuo Z. Radix Puerariae: an overview of its chemistry, pharmacology, pharmacokinetics, and clinical use. J. Clin. Pharmacol. 53: 787–811 (2013).CrossRefGoogle Scholar
  36. 36.
    Zhang JT, Liu Y, Qu ZhW, Zhang XL, Xiao HL. Influence of ginsenoside Rb1 and Rg1 on some central neurotransmitter receptors and protein biosynthesis in mouse brain. Acta Pharm. Sin. 23: 12–16 (1988).Google Scholar

Copyright information

© The Korean Society of Food Science and Technology and Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  • Young-Min Seo
    • 1
    • 2
  • Soo Jung Choi
    • 3
  • Chan Kyu Park
    • 1
  • Min Chul Gim
    • 1
  • Dong-Hoon Shin
    • 1
  1. 1.Department of Food and BiotechnologyKorea UniversitySeoulRepublic of Korea
  2. 2.Laboratory of Product Development, R&D HeadquartersKorea Ginseng CorporationDaejeonRepublic of Korea
  3. 3.Functional Food Research CenterKorea UniversitySeoulRepublic of Korea

Personalised recommendations