DOI QR코드

DOI QR Code

The psychopharmacological activities of Vietnamese ginseng in mice: characterization of its psychomotor, sedative-hypnotic, antistress, anxiolytic, and cognitive effects

  • dela Pena, Irene Joy I. (Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University) ;
  • Kim, Hee Jin (Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University) ;
  • Botanas, Chrislean Jun (Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University) ;
  • de la Pena, June Bryan (Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University) ;
  • Van Le, Thi Hong (School of Pharmacy, University of Medicine and Pharmacy) ;
  • Nguyen, Minh Duc (School of Pharmacy, University of Medicine and Pharmacy) ;
  • Park, Jeong Hill (Faculty of Pharmacy, Ton Duc Thang University) ;
  • Cheong, Jae Hoon (Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University)
  • Received : 2015.10.29
  • Accepted : 2016.03.10
  • Published : 2017.04.15

Abstract

Background: Panax vietnamensis Ha et Grushv. or Vietnamese ginseng (VG) is a recently discovered ginseng species. Studies on its chemical constituents have shown that VG is remarkably rich in ginseng saponins, particularly ocotillol saponins. However, the psychopharmacological effects of VG have not been characterized. Thus, in the present study we screened the psychopharmacological activities of VG in mice. Methods: VG extract (VGE) was orally administered to mice at various dosages to evaluate its psychomotor (open-field and rota-rod tests), sedative-hypnotic (pentobarbital-induced sleeping test), anti-stress (cold swimming test), anxiolytic (elevated plus-maze test), and cognitive (Y-maze and passive-avoidance tests) effects. Results: VGE treatment increased the spontaneous locomotor activity, enhanced the endurance to stress, reduced the anxiety-like behavior, and ameliorated the scopolamine-induced memory impairments in mice. In addition, VGE treatment did not alter the motor balance and coordination of mice and did not potentiate pentobarbital-induced sleep, indicating that VGE has no sedative-hypnotic effects. The effects of VGE were comparable to those of the Korean Red Ginseng extract. Conclusion: VG, like other ginseng products, has significant and potentially useful psychopharmacological effects. This includes, but is not limited to, psychomotor stimulation, anxiolytic, antistress, and memory enhancing effects.

Keywords

References

  1. 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 2013;37:8-29. https://doi.org/10.5142/jgr.2013.37.8
  2. Attele AS, Wu JA, Yuan CS. Ginseng pharmacology: multiple constituents and multiple actions. Biochem Pharmacol 1999;58:1685-93. https://doi.org/10.1016/S0006-2952(99)00212-9
  3. Zhao H, Li Q, Pei X, Zhang Z, Yang R, Wang J, Li Y. Long-term ginsenoside administration prevents memory impairment in aged C57BL/6J mice by upregulating the synaptic plasticity-related proteins in hippocampus. Behav Brain Res 2009;201:311-7. https://doi.org/10.1016/j.bbr.2009.03.002
  4. Lee B, Sur B, Park J, Kim SH, Kwon S, Yeom M, Shim I, Lee H, Hahm DH. Ginsenoside Rg3 alleviates lipopolysaccharide-induced learning and memory impairments by anti-inflammatory activity in rats. Biomol Ther (Seoul) 2013;21:381-90. https://doi.org/10.4062/biomolther.2013.053
  5. Kennedy D, Scholey A. Ginseng: potential for the enhancement of cognitive performance and mood. Pharmacol Biochem Behav 2003;75:687-700. https://doi.org/10.1016/S0091-3057(03)00126-6
  6. Radad K, Gille G, Liu L, Rausch WD. Use of ginseng in medicine with emphasis on neurodegenerative disorders. J Pharmacol Sci 2006;100:175-86. https://doi.org/10.1254/jphs.CRJ05010X
  7. Le THV, Lee SY, Kim TR, Kim JY, Kwon SW, Nguyen NK, Park JH, Nguyen MD. Processed Vietnamese ginseng: preliminary results in chemistry and biological activity. J Ginseng Res 2014;38:154-9. https://doi.org/10.1016/j.jgr.2013.11.015
  8. Dela Pena I, Yoon SY, Kim HJ, Park S, Hong EY, Ryu JH, Park IH, Cheong JH. Effects of ginseol k-g3, an Rg3-enriched fraction, on scopolamine-induced memory impairment and learning deficit in mice. J Ginseng Res 2014;38:1-7. https://doi.org/10.1016/j.jgr.2013.11.003
  9. Park JH, Cha HY, Seo JJ, Hong JT, Han K, Oh KW. Anxiolytic-like effects of ginseng in the elevated plus-maze model: comparison of red ginseng and sun ginseng. Prog Neuropsychopharmacol Biol Psychiatry 2005;29:895-900. https://doi.org/10.1016/j.pnpbp.2005.04.016
  10. Van Le TH, Lee SY, Lee GJ, Nguyen NK, Park JH, Nguyen MD. Effects of steaming on saponin compositions and antiproliferative activity of Vietnamese ginseng. J Ginseng Res 2015;39:274-8. https://doi.org/10.1016/j.jgr.2015.01.006
  11. Lu G, Zhou Q, Sun S, Leung KS, Zhang H, Zhao Z. Differentiation of Asian ginseng, American ginseng and Notoginseng by Fourier transform infrared spectroscopy combined with two-dimensional correlation infrared spectroscopy. J Mol Struct 2008;883-884:91-8. https://doi.org/10.1016/j.molstruc.2007.12.008
  12. Yamasaki K. Bioactive saponins in Vietnamese ginseng, Panax vietnamensis. Pharm Biol 2000;38:16-24. https://doi.org/10.1076/phbi.38.6.16.5956
  13. Huong NT, Matsumoto K, Kasai R, Yamasaki K, Watanabe H. In vitro antioxidant activity of Vietnamese ginseng saponin and its components. Biol Pharm Bull 1998;21:978-81. https://doi.org/10.1248/bpb.21.978
  14. Nguyen MD, Kasai R, Ohtani K, Ito A, Nguyen TN, Yamasaki K, Tanaka O. Saponins from Vietnamese ginseng, Panax vietnamensis Ha et Grushv. collected in central Vietnam. III. Chem Pharm Bull 1994;42:634-40. https://doi.org/10.1248/cpb.42.634
  15. Nguyen MD, Kasai R, Yamasaki K, Nguyen TN, Tanaka O. New dammarane saponins from Vietnamese ginseng. In: Chong-Ren Y, Osamu T, editors. Studies in plant science, vol. 6. Philadelphia, PA: Elsevier; 1999. p. 77-82.
  16. Jeong SM, Nah SY. Ginseng and ion channels: are ginsenosides, active component of Panax ginseng, differential modulator of ion channels? J Ginseng Res 2005;29:19-26. https://doi.org/10.5142/JGR.2005.29.1.019
  17. Park JD, Kim DS, Kwon HY, Son SK, Lee YH, Baek NI, Kim SI, Rhee DK. Effects of ginseng saponin on modulation of multidrug resistance. Arch Pharm Res 1996;19:213-8. https://doi.org/10.1007/BF02976892
  18. Tran LQ, Adnyana I, Tezuka Y, Nagaoka T, Tran Q, Kadota S. Triterpene saponins from Vietnamese ginseng (Panax vietnamensis) and their hepatocytoprotective activity. J Nat Prod 2001;64:456-61. https://doi.org/10.1021/np000393f
  19. Nhut DT, Hai NT, Huy NP, Chien HX, Nam NB. New achievements in Panax vietnamensis research. In: Jain SM, Dutta Gupta S, editors. Biotechnology of neglected and underutilized crops. Dordrecht, the Netherlands: Springer Science+Business Media; 2013. p. 43-57.
  20. Dong NT, Luan TC, Huong NTT.NgocLinh ginseng andsomemedicinalplantsbelong to ginseng family. Vietnam: Science and Technology Publishing House; 2007.
  21. Noldus LP, Spink AJ, Tegelenbosch RA. Ethovision: a versatile video tracking system for automation of behavioral experiments. Behav Res Methods 2001;33:398-414. https://doi.org/10.3758/BF03195394
  22. Dela Pena IJ, Hong E, Kim HJ, de la Pena JB, Woo TS, Lee YS, Cheong JH. Artemisia capillaris Thunberg produces sedative-hypnotic effects in mice, which are probably mediated through potentiation of the GABAA receptor. Am J Chin Med 2015;43:667-79. https://doi.org/10.1142/S0192415X1550041X
  23. Dela Pena IJ, Lee HL, Yoon SY, de la Pena JB, Kim HK, Hong EY, Cheong JH. The ethanol extract of Cirsium japonicum increased chloride ion influx through stimulating Gaba(a) receptor in human neuroblastoma cells and exhibited anxiolytic-like effects in mice. Drug Discov Ther 2013;7:18-23.
  24. Gould TD, Dao DT, Kovacsics CE. The Open field test. Neuromethods. In: Gould Todd D, editor. Mood and anxiety-related phenotypes in mice. Humana Press; 2009. p. 1-20.
  25. Tan SJ, Li N, Zhou F, Dong QT, Zhang XD, Chen BC, Yu Z. Ginsenoside Rb1 improves energy metabolism in the skeletal muscle of an animal model of postoperative fatigue syndrome. J Surg Res 2014;191:344-9. https://doi.org/10.1016/j.jss.2014.04.042
  26. Wang ZJ, Sun L, Peng W, Ma S, Zhu C, Fu F, Heinbockel T. Ginseng derivative ocotillol enhances neuronal activity through increased glutamate release: a possible mechanism underlying increased spontaneous locomotor activity in mice. Neuroscience 2011;195:1-8. https://doi.org/10.1016/j.neuroscience.2011.08.002
  27. Euaruksakul P, Tansawat R, Rodsiri R. Ginseng extract G115 improves locomotor function in rotenone-induced parkinsonism rats via an antioxidant effect. Songklanakarin J Sci Technol 2015;37:163-9.
  28. Farkas S, Berzsenyi P, Karpati E, Kocsis P, Tarnawa I. Simple pharmacological test battery to assess efficacy and side effect profile of centrally acting muscle relaxant drugs. J Pharmacol Toxicol Methods 2005;52:264-73. https://doi.org/10.1016/j.vascn.2004.11.005
  29. Hosseinzadeh H, Noraei NB. Anxiolytic and hypnotic effect of Crocus sativus aqueous extract and its constituents, crocin, and safranal, in mice. Phytother Res 2009;23:768-74. https://doi.org/10.1002/ptr.2597
  30. MaY, Han H, Eun JS, Kim HC, Hong JT, Oh KW. Sanjoinine A isolated from Zizyphi spinosi semen augments pentobarbital-induced sleeping behaviors through the modification of gabaergic systems. Biol Pharm Bull 2007;30:1748-53. https://doi.org/10.1248/bpb.30.1748
  31. Huong NTT, Matsumoto K, Yamasaki K, Duc NM, Nham NT, Watanabe H. Effects of majonoside-R2 on pentobarbital sleep and gastric lesion in psychologically stressed mice. Pharmacol Biochem Behav 1996;53:957-63. https://doi.org/10.1016/0091-3057(95)02147-7
  32. Lee CI, Kim CS, Han JY, Oh EH, Oh KW, Eun JS. Repeated administration of Korea red ginseng extract increases non-rapid eye movement sleep via GABAAergic systems. J Ginseng Res 2012;36:403-10. https://doi.org/10.5142/jgr.2012.36.4.403
  33. Choi JY, Woo TS, Yoon SY, dela Pena IC, Choi YJ, Ahn HS, Lee YS, Yu GY, Cheong JH. Red ginseng supplementation more effectively alleviates psychological than physical fatigue. J Ginseng Res 2011;35:331-8. https://doi.org/10.5142/jgr.2011.35.3.331
  34. Nguyen TT, Matsumoto K, Yamasaki K, Nguyen MD, Nguyen TN, Watanabe H. Crude saponin extracted from Vietnamese ginseng and its major constituent majonoside-R2 attenuate the psychological stress- and foot-shock stressinduced antinociception in mice. Pharmacol Biochem Behav 1995;52:427-32. https://doi.org/10.1016/0091-3057(95)00133-H
  35. Huong NT, Matsumoto K, Yamasaki K, Duc NM, Nahm NT, Watanabe H. Effects of Vietnamese ginseng on opioid agonist- and conditioned fear stress-induced antinociception. Phytomedicine 1996;3:33-9. https://doi.org/10.1016/S0944-7113(96)80007-9
  36. Yobimoto K, Matsumoto K, Huong NT, Kasai R, Yamasaki K, Watanabe H. Suppressive effects of Vietnamese ginseng saponin and its major component majonoside-R2 on psychological stress-induced enhancement of lipid peroxidation in the mouse brain. Pharmacol Biochem Behav 2000;66:661-5. https://doi.org/10.1016/S0091-3057(00)00257-4
  37. Oliynyk S, Oh S. Actoprotective effect of ginseng: improving mental and physical performance. J Ginseng Res 2013;37:144-66. https://doi.org/10.5142/jgr.2013.37.144
  38. Pellow S, File SE. Anxiolytic and anxiogenic drug effects on exploratory activity in an elevated plus-maze: a novel test of anxiety in the rat. Pharmacol Biochem Behav 1986;24:525-9. https://doi.org/10.1016/0091-3057(86)90552-6
  39. Rex A, Stephens DN, Fink H. “Anxiolytic” action of diazepam and abecarnil in a modified open field test. Pharmacol Biochem Behav 1996;53:1005-11. https://doi.org/10.1016/0091-3057(95)02121-3
  40. Carr MN, Bekku N, Yoshimura H. Identification of anxiolytic ingredients in ginseng root using the elevated plus-maze test in mice. Eur J Pharmacol 2006;531:160-5. https://doi.org/10.1016/j.ejphar.2005.12.014
  41. Bhattacharya SK, Mitra SK. Anxiolytic activity of Panax ginseng roots: an experimental study. J Ethnopharmacol 1991;34:87-92. https://doi.org/10.1016/0378-8741(91)90193-H
  42. Cha HY, Park JH, Hong JT, Yoo HS, Song S, Hwang BY, Eun JS, Oh KW. Anxiolytic-like effects of ginsenosides on the elevated plus-maze model in mice. Biol Pharm Bull 2005;28:1621-5. https://doi.org/10.1248/bpb.28.1621
  43. Yang JH, Han SJ, Ryu JH, Jang IS, Kim DH. Ginsenoside Rh2 ameliorates scopolamine-induced learning deficit in mice. Biol Pharm Bull 2009;32:1710-5. https://doi.org/10.1248/bpb.32.1710
  44. Olton DS, Papas BC. Spatial memory and hippocampal function. Neuropsychologia 1979;17:669-82. https://doi.org/10.1016/0028-3932(79)90042-3
  45. Klinkenberg I, Blokland A. The validity of scopolamine as a pharmacological model for cognitive impairment: a review of animal behavioral studies. Neurosci Biobehav Rev 2010;34:1307-50. https://doi.org/10.1016/j.neubiorev.2010.04.001
  46. Lorenzini CA, Baldi E, Bucherelli C, Sacchetti B, Tassoni G. Role of dorsal hippocampus in acquisition, consolidation and retrieval of rat's passive avoidance response: a tetrodotoxin functional inactivationstudy. Brain Res 1996;730:32-9. https://doi.org/10.1016/0006-8993(96)00427-1
  47. 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 1999;66:123-9. https://doi.org/10.1016/S0378-8741(98)00190-1

Cited by

  1. Phytoconstituents and Biological Activities of Panax vietnamensis (Vietnamese Ginseng): A Precious Ginseng and Call for Further Research-A systematic review vol.13, pp.10, 2017, https://doi.org/10.1177/1934578x1801301036
  2. Effects of Panax ginseng C.A. Meyer extract on the offspring of adult mice with maternal immune activation vol.18, pp.4, 2017, https://doi.org/10.3892/mmr.2018.9417
  3. Protective effects of cultured and fermented ginseng extracts against scopolamine-induced memory loss in a mouse model vol.34, pp.1, 2017, https://doi.org/10.5625/lar.2018.34.1.37
  4. The Effects of Donepezil, an Acetylcholinesterase Inhibitor, on Impaired Learning and Memory in Rodents vol.26, pp.3, 2017, https://doi.org/10.4062/biomolther.2017.189
  5. Substituted Aminobenzothiazole Derivatives of Tacrine: Synthesis and Study on Learning and Memory Impairment in Scopolamine-Induced Model of Amnesia in Rat vol.19, pp.1, 2017, https://doi.org/10.2174/1389557518666180716122608
  6. Screening and determination for potential acetylcholinesterase inhibitory constituents from ginseng stem–leaf saponins using ultrafiltration (UF)‐LC‐ESI‐MS2 vol.30, pp.1, 2017, https://doi.org/10.1002/pca.2787
  7. Korean red ginseng promotes hippocampal neurogenesis in mice vol.15, pp.5, 2017, https://doi.org/10.4103/1673-5374.268905
  8. Korean Red Ginseng Regulates Intestinal Tight Junction and Inflammation in the Colon of a Parkinson's Disease Mouse Model vol.23, pp.12, 2017, https://doi.org/10.1089/jmf.2019.4640