Journal of Ginseng Research

  • 제37권1호
  • /
  • Pages.8-29
  • /
  • 2013
  • /
  • 1226-8453(pISSN)
  • /
  • 2093-4947(eISSN)
고려인삼학회 (The Korean Society of Ginseng)
권호 표지
DOI QR코드

DOI QR Code

A comprehensive review of the therapeutic and pharmacological effects of ginseng and ginsenosides in central nervous system

  • Kim, Hee Jin (Department of Pharmacology, School of Medicine and Advanced Institute of Biomedical Science and Technology, Konkuk University) ;
  • Kim, Pitna (Department of Pharmacology, School of Medicine and Advanced Institute of Biomedical Science and Technology, Konkuk University) ;
  • Shin, Chan Young (Department of Pharmacology, School of Medicine and Advanced Institute of Biomedical Science and Technology, Konkuk University)
  • 투고 : 2012.06.05
  • 심사 : 2012.07.31
  • 발행 : 2013.01.15
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Ginseng is one of the most widely used herbal medicines in human. Central nervous system (CNS) diseases are most widely investigated diseases among all others in respect to the ginseng's therapeutic effects. These include Alzheimer's disease, Parkinson's disease, cerebral ischemia, depression, and many other neurological disorders including neurodevelopmental disorders. Not only the various types of diseases but also the diverse array of target pathways or molecules ginseng exerts its effect on. These range, for example, from neuroprotection to the regulation of synaptic plasticity and from regulation of neuroinflammatory processes to the regulation of neurotransmitter release, too many to mention. In general, ginseng and even a single compound of ginsenoside produce its effects on multiple sites of action, which make it an ideal candidate to develop multi-target drugs. This is most important in CNS diseases where multiple of etiological and pathological targets working together to regulate the final pathophysiology of diseases. In this review, we tried to provide comprehensive information on the pharmacological and therapeutic effects of ginseng and ginsenosides on neurodegenerative and other neurological diseases. Side by side comparison of the therapeutic effects in various neurological disorders may widen our understanding of the therapeutic potential of ginseng in CNS diseases and the possibility to develop not only symptomatic drugs but also disease modifying reagents based on ginseng.

키워드

참고문헌

  1. 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;883-884:91-98. https://doi.org/10.1016/j.molstruc.2007.12.008
  2. Tachikawa E, Kudo K, Harada K, Kashimoto T, Miyate Y, Kakizaki A, Takahashi E. Effects of ginseng saponins on responses induced by various receptor stimuli. Eur J Pharmacol 1999;369:23-32. https://doi.org/10.1016/S0014-2999(99)00043-6
  3. Sung H, Jung YS, Cho YK. Beneficial effects of a combination of Korean red ginseng and highly active antiretroviral therapy in human immunodeficiency virus type 1-infected patients. Clin Vaccine Immunol 2009;16:1127-1131. https://doi.org/10.1128/CVI.00013-09
  4. Radad K, Moldzio R, Rausch WD. Ginsenosides and their CNS targets. CNS Neurosci Ther 2011;17:761-768. https://doi.org/10.1111/j.1755-5949.2010.00208.x
  5. Jesky R, Hailong C. Are herbal compounds the next frontier for alleviating learning and memory impairments? An integrative look at memory, dementia and the promising therapeutics of traditional chinese medicines. Phytother Res 2011;25:1105-1118. https://doi.org/10.1002/ptr.3388
  6. Radad K, Gille G, Liu L, Rausch WD. Use of ginseng in medicine with emphasis on neurodegenerative disorders. J Pharmacol Sci 2006;100:175-186. https://doi.org/10.1254/jphs.CRJ05010X
  7. Tohda C, Matsumoto N, Zou K, Meselhy MR, Komatsu K. Axonal and dendritic extension by protopanaxadiol-type saponins from ginseng drugs in SK-N-SH cells. Jpn J Pharmacol 2002;90:254-262. https://doi.org/10.1254/jjp.90.254
  8. Tohda C, Matsumoto N, Zou K, Meselhy MR, Komatsu K. Abeta(25-35)-induced memory impairment, axonal atrophy, and synaptic loss are ameliorated by M1, A metabolite of protopanaxadiol-type saponins. Neuropsychopharmacology 2004;29:860-868. https://doi.org/10.1038/sj.npp.1300388
  9. Sugaya A, Yuzurihara M, Tsuda T, Yasuda K, Kajiwara K, Sugaya E. Proliferative effect of ginseng saponin on neurite extension of primary cultured neurons of the rat cerebral cortex. J Ethnopharmacol 1988;22:173-181. https://doi.org/10.1016/0378-8741(88)90125-0
  10. Nishiyama N, Cho SI, Kitagawa I, Saito H. Malonylginsenoside Rb1 potentiates nerve growth factor (NGF)-induced neurite outgrowth of cultured chick embryonic dorsal root ganglia. Biol Pharm Bull 1994;17:509-513. https://doi.org/10.1248/bpb.17.509
  11. Wang XY, Zhang JT. Effect of ginsenoside Rb1 on long-term potentiation in the dentate gyrus of anaesthetized rats. J Asian Nat Prod Res 2003;5:1-4. https://doi.org/10.1080/10286020290029009
  12. Kurimoto H, Nishijo H, Uwano T, Yamaguchi H, Zhong YM, Kawanishi K, Ono T. Effects of nonsaponin fraction of red ginseng on learning deficits in aged rats. Physiol Behav 2004;82:345-355. https://doi.org/10.1016/j.physbeh.2004.04.001
  13. Qi D, Zhu Y, Wen L, Liu Q, Qiao H. Ginsenoside Rg1 restores the impairment of learning induced by chronic morphine administration in rats. J Psychopharmacol 2009;23:74-83. https://doi.org/10.1177/0269881107082950
  14. Bae MY, Cho JH, Choi IS, Park HM, Lee MG, Kim DH, Jang IS. Compound K, a metabolite of ginsenosides, facilitates spontaneous GABA release onto CA3 pyramidal neurons. J Neurochem 2010;114:1085-1096.
  15. Jiang B, Xiong Z, Yang J, Wang W, Wang Y, Hu ZL, Wang F, Chen JG. Antidepressant-like effects of ginsenoside Rg1 are due to activation of the BDNF signalling pathway and neurogenesis in the hippocampus. Br J Pharmacol 2012;166:1872-1887. https://doi.org/10.1111/j.1476-5381.2012.01902.x
  16. Cheng Y, Shen LH, Zhang JT. Anti-amnestic and anti-aging effects of ginsenoside Rg1 and Rb1 and its mechanism of action. Acta Pharmacol Sin 2005;26:143-149. https://doi.org/10.1111/j.1745-7254.2005.00034.x
  17. Wang L, Kisaalita WS. Administration of BDNF/ginsenosides combination enhanced synaptic development in human neural stem cells. J Neurosci Methods 2011;194:274-282. https://doi.org/10.1016/j.jneumeth.2010.10.025
  18. Li N, Liu B, Dluzen DE, Jin Y. Protective effects of ginsenoside Rg2 against glutamate-induced neurotoxicity in PC12 cells. J Ethnopharmacol 2007;111:458-463. https://doi.org/10.1016/j.jep.2006.12.015
  19. Nah SY, Kim DH, Rhim H. Ginsenosides: are any of them candidates for drugs acting on the central nervous system? CNS Drug Rev 2007;13:381-404.
  20. Tu LH, Ma J, Liu HP, Wang RR, Luo J. The neuroprotective effects of ginsenosides on calcineurin activity and tau phosphorylation in SY5Y cells. Cell Mol Neurobiol 2009;29:1257-1264. https://doi.org/10.1007/s10571-009-9421-3
  21. Hu SQ, Yu HM, Liu TS, Yang DJ, Chen XZ, He CJ. Neuroprotective effects of water extracts of American ginseng on SH-SY5Y cells apoptosis induced by Abeta25-35. Zhong Yao Cai 2008;31:1373-1377.
  22. Xie X, Wang HT, Li CL, Gao XH, Ding JL, Zhao HH, Lu YL. Ginsenoside Rb1 protects PC12 cells against $\beta$-amyloid-induced cell injury. Mol Med Report 2010;3:635-639.
  23. Wang YH, Du GH. Ginsenoside Rg1 inhibits beta-secretase activity in vitro and protects against Abeta-induced cytotoxicity in PC12 cells. J Asian Nat Prod Res 2009;11:604-612. https://doi.org/10.1080/10286020902843152
  24. Shieh PC, Tsao CW, Li JS, Wu HT, Wen YJ, Kou DH, Cheng JT. Role of pituitary adenylate cyclase-activating polypeptide (PACAP) in the action of ginsenoside Rh2 against beta-amyloid-induced inhibition of rat brain astrocytes. Neurosci Lett 2008;434:1-5. https://doi.org/10.1016/j.neulet.2007.12.032
  25. Lin WM, Zhang YM, Moldzio R, Rausch WD. Ginsenoside Rd attenuates neuroinflammation of dopaminergic cells in culture. J Neural Transm Suppl 2007;(72):105-112.
  26. Shen T, Lee J, Park MH, Lee YG, Rho HS, Kwak YS, Rhee MH, Park YC, Cho JY: Ginsenoside Rp1, a ginsenoside derivative, blocks promoter activation of iNOS and COX-2 genes by suppression of an IKKb-mediated NF-kB pathway in HEK293 cells. J Ginseng Res 2011;35:200-208. https://doi.org/10.5142/jgr.2011.35.2.200
  27. Wu CF, Bi XL, Yang JY, Zhan JY, Dong YX, Wang JH, Wang JM, Zhang R, Li X. Differential effects of ginsenosides on NO and TNF-alpha production by LPS-activated N9 microglia. Int Immunopharmacol 2007;7:313-320. https://doi.org/10.1016/j.intimp.2006.04.021
  28. Bae EA, Kim EJ, Park JS, Kim HS, Ryu JH, Kim DH. Ginsenosides Rg3 and Rh2 inhibit the activation of AP-1 and protein kinase A pathway in lipopolysaccharide/interferon-gamma-stimulated BV-2 microglial cells. Planta Med 2006;72:627-633. https://doi.org/10.1055/s-2006-931563
  29. Wang Y, Liu J, Zhang Z, Bi P, Qi Z, Zhang C. Anti-neuroinflammation effect of ginsenoside Rbl in a rat model of Alzheimer disease. Neurosci Lett 2011;487:70-72. https://doi.org/10.1016/j.neulet.2010.09.076
  30. Park JS, Shin JA, Jung JS, Hyun JW, Van Le TK, Kim DH, Park EM, Kim HS. Anti-inflammatory mechanism of compound K in activated microglia and its neuroprotective effect on experimental stroke in mice. J Pharmacol Exp Ther 2012;341:59-67. https://doi.org/10.1124/jpet.111.189035
  31. He W, Zhu Z. Effect of Panax notoginseng saponins on intercellular adhesion molecule-1 expression and neutrophil infiltration in cerebral infarction tissue of rats. Zhong Yao Cai 2005;28:403-405.
  32. Joo SS, Won TJ, Lee DI. Reciprocal activity of ginsenosides in the production of proinflammatory repertoire, and their potential roles in neuroprotection in vivo. Planta Med 2005;71:476-481. https://doi.org/10.1055/s-2005-864145
  33. Zhao H, Li Q, Zhang Z, Pei X, Wang J, Li Y. Long-term ginsenoside consumption prevents memory loss in aged SAMP8 mice by decreasing oxidative stress and up-regulating the plasticity-related proteins in hippocampus. Brain Res 2009;1256:111-122. https://doi.org/10.1016/j.brainres.2008.12.031
  34. Jung JS, Shin JA, Park EM, Lee JE, Kang YS, Min SW, Kim DH, Hyun JW, Shin CY, Kim HS. Anti-inflammatory mechanism of ginsenoside Rh1 in lipopolysaccharide-stimulated microglia: critical role of the protein kinase A pathway and hemeoxygenase-1 expression. J Neurochem 2010;115:1668-1680. https://doi.org/10.1111/j.1471-4159.2010.07075.x
  35. Song SB, Tung NH, Quang TH, Ngan NT, Kim KE, Kim YH: Inhibition of TNF-$\alpha$-mediated NF-$\kappa B$ transcriptional activity in HepG2 cells by dammarane-type saponins from Panax ginseng leaves. J Ginseng Res 2012; 36:146-152. https://doi.org/10.5142/jgr.2012.36.2.146
  36. Chen F, Eckman EA, Eckman CB. Reductions in levels of the Alzheimer's amyloid beta peptide after oral administration of ginsenosides. FASEB J 2006;20:1269-1271. https://doi.org/10.1096/fj.05-5530fje
  37. Choi RC, Zhu JT, Leung KW, Chu GK, Xie HQ, Chen VP, Zheng KY, Lau DT, Dong TT, Chow PC et al. A flavonol glycoside, isolated from roots of Panax notoginseng, reduces amyloid-beta-induced neurotoxicity in cultured neurons: signaling transduction and drug development for Alzheimer’s disease. J Alzheimers Dis 2010;19:795-811. https://doi.org/10.3233/JAD-2010-1293
  38. Chen LM, Lin ZY, Zhu YG, Lin N, Zhang J, Pan XD, Chen XC. Ginsenoside Rg1 attenuates $\beta$-amyloid generation via suppressing $PPAR\gamma$-regulated BACE1 activity in N2a-APP695 cells. Eur J Pharmacol 2012;675:15-21. https://doi.org/10.1016/j.ejphar.2011.11.039
  39. Fang F, Chen X, Huang T, Lue LF, Luddy JS, Yan SS. Multi-faced neuroprotective effects of Ginsenoside Rg1 in an Alzheimer mouse model. Biochim Biophys Acta 2012;1822:286-292. https://doi.org/10.1016/j.bbadis.2011.10.004
  40. Shi C, Na N, Zhu X, Xu J. Estrogenic effect of ginsenoside Rg1 on APP processing in post-menopausal platelets. Platelets 2012; Epub ahead of print.
  41. Shi C, Zheng DD, Fang L, Wu F, Kwong WH, Xu J. Ginsenoside Rg1 promotes nonamyloidgenic cleavage of APP via estrogen receptor signaling to MAPK/ERK and PI3K/Akt. Biochim Biophys Acta 2012;1820:453-460. https://doi.org/10.1016/j.bbagen.2011.12.005
  42. Joo SS, Lee DI. Potential effects of microglial activation induced by ginsenoside Rg3 in rat primary culture: enhancement of type A Macrophage Scavenger Receptor expression. Arch Pharm Res 2005;28:1164-1169. https://doi.org/10.1007/BF02972981
  43. Yang L, Hao J, Zhang J, Xia W, Dong X, Hu X, Kong F, Cui X. Ginsenoside Rg3 promotes beta-amyloid peptide degradation by enhancing gene expression of neprilysin. J Pharm Pharmacol 2009;61:375-380. https://doi.org/10.1211/jpp.61.03.0013
  44. Iwata N, Tsubuki S, Takaki Y, Shirotani K, Lu B, Gerard NP, Gerard C, Hama E, Lee HJ, Saido TC. Metabolic regulation of brain Abeta by neprilysin. Science 2001;292:1550-1552. https://doi.org/10.1126/science.1059946
  45. Xie YH, Chen XC, Zhang J, Huang TW, Song JQ, Fang YX, Pan XD, Lin ZY. Ginsenoside Rb1 attenuates beta-amyloid peptide(25-35)-induced hyperphosphorylation of tau protein through CDK5 signal pathway. Yao Xue Xue Bao 2007;42:828-832.
  46. Zhao R, Zhang Z, Song Y, Wang D, Qi J, Wen S. Implication of phosphatidylinositol-3 kinase/Akt/glycogen synthase kinase-$3\beta$ pathway in ginsenoside Rb1's attenuation of beta-amyloid-induced neurotoxicity and tau phosphorylation. J Ethnopharmacol 2011;133:1109-1116. https://doi.org/10.1016/j.jep.2010.11.054
  47. Li X, Liu Y, Zhang X, Yuan H, Quan Q. Effect of ginsenoside Rg1 on expressions of phosphory protein tau and N-methyl-D-aspartate receptor subunits NR1 and NR2B in rat brain slice model of Alzheimer's disease. Zhongguo Zhong Yao Za Zhi 2010;35:3339-3343.
  48. Li L, Liu J, Yan X, Qin K, Shi M, Lin T, Zhu Y, Kang T, Zhao G. Protective effects of ginsenoside Rd against okadaic acid-induced neurotoxicity in vivo and in vitro. J Ethnopharmacol 2011;138:135-141. https://doi.org/10.1016/j.jep.2011.08.068
  49. Hao W, Xing-Jun W, Yong-Yao C, Liang Z, Yang L, Hong-Zhuan C. Up-regulation of M1 muscarinic recep tors expressed in CHOm1 cells by panaxynol via cAMP pathway. Neurosci Lett 2005;383:121-126 https://doi.org/10.1016/j.neulet.2005.03.062
  50. Xue JF, Liu ZJ, Hu JF, Chen H, Zhang JT, Chen NH. Ginsenoside Rb1 promotes neurotransmitter release by modulating phosphorylation of synapsins through a cAMP-dependent protein kinase pathway. Brain Res 2006;1106:91-98. https://doi.org/10.1016/j.brainres.2006.05.106
  51. Benishin CG, Lee R, Wang LC, Liu HJ. Effects of ginsenoside Rb1 on central cholinergic metabolism. Pharmacology 1991;42:223-229. https://doi.org/10.1159/000138801
  52. Benishin CG. Actions of ginsenoside Rb1 on choline uptake in central cholinergic nerve endings. Neurochem Int 1992;21:1-5. https://doi.org/10.1016/0197-0186(92)90061-U
  53. Salim KN, McEwen BS, Chao HM. Ginsenoside Rb1 regulates ChAT, NGF and trkA mRNA expression in the rat brain. Brain Res Mol Brain Res 1997;47:177-182. https://doi.org/10.1016/S0169-328X(97)00042-9
  54. Zhang JT, Qu ZW, Liu Y, Deng HL. Preliminary study on antiamnestic mechanism of ginsenoside Rg1 and Rb1. Chin Med J (Engl) 1990;103:932-938.
  55. Lee TF, Shiao YJ, Chen CF, Wang LC. Effect of ginseng saponins on beta-amyloid-suppressed acetylcholine release from rat hippocampal slices. Planta Med 2001;67:634-637. https://doi.org/10.1055/s-2001-17366
  56. Lee NH, Son CG. Systematic review of randomized controlled trials evaluating the efficacy and safety of ginseng. J Acupunct Meridian Stud 2011;4:85-97. https://doi.org/10.1016/S2005-2901(11)60013-7
  57. Heo JH, Lee ST, Chu K, Oh MJ, 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 2008;15:865-868. https://doi.org/10.1111/j.1468-1331.2008.02157.x
  58. Lee ST, Chu K, Sim JY, Heo JH, Kim M. Panax ginseng enhances cognitive performance in Alzheimer disease. Alzheimer Dis Assoc Disord 2008;22:222-226. https://doi.org/10.1097/WAD.0b013e31816c92e6
  59. Chen XC, Zhu YG, Zhu LA, Huang C, Chen Y, Chen LM, Fang F, Zhou YC, Zhao CH. Ginsenoside Rg1 attenuates dopamine-induced apoptosis in PC12 cells by suppressing oxidative stress. Eur J Pharmacol 2003;473:1-7. https://doi.org/10.1016/S0014-2999(03)01945-9
  60. Liu Q, Kou JP, Yu BY. Ginsenoside Rg1 protects against hydrogen peroxide-induced cell death in PC12 cells via inhibiting NF-$\kappa B$ activation. Neurochem Int 2011;58:119-125. https://doi.org/10.1016/j.neuint.2010.11.004
  61. Radad K, Gille G, Moldzio R, Saito H, Ishige K, Rausch WD. Ginsenosides Rb1 and Rg1 effects on survival and neurite growth of $MPP^{+}$-affected mesencephalic dopaminergic cells. J Neural Transm 2004;111:37-45. https://doi.org/10.1007/s00702-003-0063-1
  62. Chen XC, Zhou YC, Chen Y, Zhu YG, Fang F, Chen LM. Ginsenoside Rg1 reduces MPTP-induced substantia nigra neuron loss by suppressing oxidative stress. Acta Pharmacol Sin 2005;26:56-62. https://doi.org/10.1111/j.1745-7254.2005.00019.x
  63. Wang J, Xu HM, Yang HD, Du XX, Jiang H, Xie JX. Rg1 reduces nigral iron levels of MPTP-treated C57BL6 mice by regulating certain iron transport proteins. Neurochem Int 2009;54:43-48. https://doi.org/10.1016/j.neuint.2008.10.003
  64. Xu H, Jiang H, Wang J, Xie J. Rg1 protects iron-induced neurotoxicity through antioxidant and iron regulatory proteins in 6-OHDA-treated MES23.5 cells. J Cell Biochem 2010;111:1537-1545. https://doi.org/10.1002/jcb.22885
  65. Xu H, Jiang H, Wang J, Xie J. Rg1 protects the $MPP^{+}$-treated MES23.5 cells via attenuating DMT1 up-regulation and cellular iron uptake. Neuropharmacology 2010;58:488-494. https://doi.org/10.1016/j.neuropharm.2009.09.002
  66. Luo FC, Wang SD, Li K, Nakamura H, Yodoi J, Bai J. Panaxatriol saponins extracted from Panax notoginseng induces thioredoxin-1 and prevents 1-methyl-4-phenylpyridinium ion-induced neurotoxicity. J Ethnopharmacol 2010;127:419-423. https://doi.org/10.1016/j.jep.2009.10.023
  67. Luo FC, Wang SD, Qi L, Song JY, Lv T, Bai J. Protective effect of panaxatriol saponins extracted from Panax notoginseng against MPTP-induced neurotoxicity in vivo. J Ethnopharmacol 2011;133:448-453. https://doi.org/10.1016/j.jep.2010.10.017
  68. Leung KW, Yung KK, Mak NK, Chan YS, Fan TP, Wong RN. Neuroprotective effects of ginsenoside-Rg1 in primary nigral neurons against rotenone toxicity. Neuropharmacology 2007;52:827-835. https://doi.org/10.1016/j.neuropharm.2006.10.001
  69. Ge KL, Chen WF, Xie JX, Wong MS. Ginsenoside Rg1 protects against 6-OHDA-induced toxicity in MES23.5 cells via Akt and ERK signaling pathways. J Ethnopharmacol 2010;127:118-123. https://doi.org/10.1016/j.jep.2009.09.038
  70. Gao QG, Chen WF, Xie JX, Wong MS. Ginsenoside Rg1 protects against 6-OHDA-induced neurotoxicity in neuroblastoma SK-N-SH cells via IGF-I receptor and estrogen receptor pathways. J Neurochem 2009;109:1338-1347. https://doi.org/10.1111/j.1471-4159.2009.06051.x
  71. Xu L, Chen WF, Wong MS. Ginsenoside Rg1 protects dopaminergic neurons in a rat model of Parkinson's disease through the IGF-I receptor signalling pathway. Br J Pharmacol 2009;158:738-748. https://doi.org/10.1111/j.1476-5381.2009.00361.x
  72. Beamer CA, Shepherd DM. Inhibition of TLR ligand- and interferon gamma-induced murine microglial activation by Panax notoginseng. J Neuroimmune Pharmacol 2012;7:465-476. https://doi.org/10.1007/s11481-011-9333-0
  73. Van Kampen J, Robertson H, Hagg T, Drobitch R. Neuroprotective actions of the ginseng extract G115 in two rodent models of Parkinson's disease. Exp Neurol 2003;184:521-529. https://doi.org/10.1016/j.expneurol.2003.08.002
  74. Rudakewich M, Ba F, Benishin CG. Neurotrophic and neuroprotective actions of ginsenosides Rb(1) and Rg(1). Planta Med 2001;67:533-537. https://doi.org/10.1055/s-2001-16488
  75. Dawson TM, Ko HS, Dawson VL. Genetic animal models of Parkinson's disease. Neuron 2010;66:646-661. https://doi.org/10.1016/j.neuron.2010.04.034
  76. Wu J, Jeong HK, Bulin SE, Kwon SW, Park JH, Bezprozvanny I. Ginsenosides protect striatal neurons in a cellular model of Huntington’s disease. J Neurosci Res 2009;87:1904-1912. https://doi.org/10.1002/jnr.22017
  77. Jiang F, DeSilva S, Turnbull J. Beneficial effect of ginseng root in SOD-1 (G93A) transgenic mice. J Neurol Sci 2000;180:52-54. https://doi.org/10.1016/S0022-510X(00)00421-4
  78. Shah ZA, Gilani RA, Sharma P, Vohora SB. Cerebroprotective effect of Korean ginseng tea against global and focal models of ischemia in rats. J Ethnopharmacol 2005;101:299-307. https://doi.org/10.1016/j.jep.2005.05.002
  79. Kim YO, Kim HJ, Kim GS, Park HG, Lim SJ, Seong NS, Ham YW, Lee SD, Jang KH, Jung KH et al. Panax ginseng protects against global ischemia injury in rat hippocampus. J Med Food 2009;12:71-76. https://doi.org/10.1089/jmf.2007.0614
  80. Chu GX, Chen X. Anti-lipid peroxidation and protection of ginsenosides against cerebral ischemia-reperfusion injuries in rats. Zhongguo Yao Li Xue Bao 1990;11:119-123.
  81. Wen TC, Yoshimura H, Matsuda S, Lim JH, Sakanaka M. Ginseng root prevents learning disability and neuronal loss in gerbils with 5-minute forebrain ischemia. Acta Neuropathol 1996;91:15-22.
  82. Wang J, Yang LJ, Zhou CM, Zhu HM, Zhang SM. Effects of Shenfu injection on hypoxic-ischemic brain damage: experiment with neonatal rats. Zhonghua Yi Xue Za Zhi 2006;86:2994-2997.
  83. Kim YC, Kim SR, Markelonis GJ, Oh TH. Ginsenosides Rb1 and Rg3 protect cultured rat cortical cells from glutamate-induced neurodegeneration. J Neurosci Res 1998;53:426-432. https://doi.org/10.1002/(SICI)1097-4547(19980815)53:4<426::AID-JNR4>3.0.CO;2-8
  84. Ye R, Li N, Han J, Kong X, Cao R, Rao Z, Zhao G. Neuroprotective effects of ginsenoside Rd against oxygen-glucose deprivation in cultured hippocampal neurons. Neurosci Res 2009;64:306-310. https://doi.org/10.1016/j.neures.2009.03.016
  85. Ye R, Kong X, Yang Q, Zhang Y, Han J, Zhao G. Ginsenoside Rd attenuates redox imbalance and improves stroke outcome after focal cerebral ischemia in aged mice. Neuropharmacology 2011;61:815-824. https://doi.org/10.1016/j.neuropharm.2011.05.029
  86. Tian J, Zhang S, Li G, Liu Z, Xu B. 20(S)-ginsenoside Rg3, a neuroprotective agent, inhibits mitochondrial permeability transition pores in rat brain. Phytother Res 2009;23:486-491. https://doi.org/10.1002/ptr.2653
  87. Zhang B, Hata R, Zhu P, Sato K, Wen TC, Yang L, Fujita H, Mitsuda N, Tanaka J, Samukawa K et al. Prevention of ischemic neuronal death by intravenous infusion of a ginseng saponin, ginsenoside Rb(1), that upregulates Bcl-x(L) expression. J Cereb Blood Flow Metab 2006;26:708-721. https://doi.org/10.1038/sj.jcbfm.9600225
  88. Park EK, Choo MK, Oh JK, Ryu JH, Kim DH. Ginsenoside Rh2 reduces ischemic brain injury in rats. Biol Pharm Bull 2004;27:433-436. https://doi.org/10.1248/bpb.27.433
  89. Ye R, Zhang X, Kong X, Han J, Yang Q, Zhang Y, Chen Y, Li P, Liu J, Shi M et al. Ginsenoside Rd attenuates mitochondrial dysfunction and sequential apoptosis after transient focal ischemia. Neuroscience 2011;178:169-180.
  90. Ye R, Yang Q, Kong X, Han J, Zhang X, Zhang Y, Li P, Liu J, Shi M, Xiong L et al. Ginsenoside Rd attenuates early oxidative damage and sequential inflammatory response after transient focal ischemia in rats. Neurochem Int 2011;58:391-398. https://doi.org/10.1016/j.neuint.2010.12.015
  91. Zhang Y, Zhou L, Zhang X, Bai J, Shi M, Zhao G. Ginsenoside-Rd attenuates TRPM7 and ASIC1a but promotes ASIC2a expression in rats after focal cerebral ischemia. Neurol Sci 2012;33:1125-1131. https://doi.org/10.1007/s10072-011-0916-6
  92. He W, Zhu Z, Liu J, Ye H, Zeng J, Huang X, Lai F. Study on therapeutic window of opportunity for Panax notoginseng saponins following focal cerebral ischemia/reperfusion injury in rats. Zhong Yao Cai 2004;27:25-27.
  93. Lee JS, Choi HS, Kang SW, Chung JH, Park HK, Ban JY, Kwon OY, Hong HP, Ko YG. Therapeutic effect of Korean red ginseng on inflammatory cytokines in rats with focal cerebral ischemia/reperfusion injury. Am J Chin Med 2011;39:83-94. https://doi.org/10.1142/S0192415X1100866X
  94. Li H, Deng CQ, Chen BY, Zhang SP, Liang Y, Luo XG. Total saponins of Panax notoginseng modulate the expression of caspases and attenuate apoptosis in rats following focal cerebral ischemia-reperfusion. J Ethnopharmacol 2009;121:412-418. https://doi.org/10.1016/j.jep.2008.10.042
  95. Lu T, Jiang Y, Zhou Z, Yue X, Wei N, Chen Z, Ma M, Xu G, Liu X. Intranasal ginsenoside Rb1 targets the brain and ameliorates cerebral ischemia/reperfusion injury in rats. Biol Pharm Bull 2011;34:1319-1324. https://doi.org/10.1248/bpb.34.1319
  96. Zhu J, Jiang Y, Wu L, Lu T, Xu G, Liu X. Suppression of local inflammation contributes to the neuroprotective effect of ginsenoside Rb1 in rats with cerebral ischemia. Neuroscience 2012;202:342-351. https://doi.org/10.1016/j.neuroscience.2011.11.070
  97. Park HJ, Shim HS, Kim KS, Shim I. The protective effect of black ginseng against transient focal ischemia-induced neuronal damage in rats. Korean J Physiol Pharmacol 2011;15:333-338. https://doi.org/10.4196/kjpp.2011.15.6.333
  98. Park SI, Jang DK, Han YM, Sunwoo YY, Park MS, Chung YA, Maeng LS, Im R, Kim MW, Jeun SS et al. Effect of combination therapy with sodium ozagrel and Panax ginseng on transient cerebral ischemia model in rats. J Biomed Biotechnol 2010;2010:893401.
  99. Sakanaka M, Zhu P, Zhang B, Wen TC, Cao F, Ma YJ, Samukawa K, Mitsuda N, Tanaka J, Kuramoto M et al. Intravenous infusion of dihydroginsenoside Rb1 prevents compressive spinal cord injury and ischemic brain damage through upregulation of VEGF and Bcl-XL. J Neurotrauma 2007;24:1037-1054. https://doi.org/10.1089/neu.2006.0182
  100. Zhang B, Matsuda S, Tanaka J, Tateishi N, Maeda N, Wen TC, Peng H, Sakanaka M. Ginsenoside Rb(1) prevents image navigation disability, cortical infarction, and thalamic degeneration in rats with focal cerebral ischemia. J Stroke Cerebrovasc Dis 1998;7:1-9. https://doi.org/10.1016/S1052-3057(98)80015-3
  101. Son HY, Han HS, Jung HW, Park YK. Panax notoginseng attenuates the infarct volume in rat ischemic brain and the inflammatory response of microglia. J Pharmacol Sci 2009;109:368-379. https://doi.org/10.1254/jphs.08197FP
  102. Zhang G, Liu A, Zhou Y, San X, Jin T, Jin Y. Panax ginseng ginsenoside-Rg2 protects memory impairment via anti-apoptosis in a rat model with vascular dementia. J Ethnopharmacol 2008;115:441-448. https://doi.org/10.1016/j.jep.2007.10.026
  103. Zhang YG, Liu TP. Influences of ginsenosides Rb1 and Rg1 on reversible focal brain ischemia in rats. Zhongguo Yao Li Xue Bao 1996;17:44-48.
  104. Zheng GQ, Cheng W, Wang Y, Wang XM, Zhao SZ, Zhou Y, Liu SJ, Wang XT. Ginseng total saponins enhance neurogenesis after focal cerebral ischemia. J Ethnopharmacol 2011;133:724-728. https://doi.org/10.1016/j.jep.2010.01.064
  105. Lim JH, Wen TC, Matsuda S, Tanaka J, Maeda N, Peng H, Aburaya J, Ishihara K, Sakanaka M. Protection of ischemic hippocampal neurons by ginsenoside Rb1, a main ingredient of ginseng root. Neurosci Res 1997;28:191-200. https://doi.org/10.1016/S0168-0102(97)00041-2
  106. Choi SR, Saji H, Iida Y, Magata Y, Yokoyama A. Ginseng pretreatment protects against transient global cerebral ischemia in the rat: measurement of local cerebral glucose utilization by [14C]deoxyglucose autoradiography. Biol Pharm Bull 1996;19:644-646. https://doi.org/10.1248/bpb.19.644
  107. Chuang CM, Hsieh CL, Lin HY, Lin JG. Panax notoginseng Burk attenuates impairment of learning and memory functions and increases ED1, BDNF and beta-secretase immunoreactive cells in chronic stage ischemia-reperfusion injured rats. Am J Chin Med 2008;36:685-693. https://doi.org/10.1142/S0192415X08006156
  108. Jiang S, Miao B, Song X, Jiang Z. Inactivation of GABA(A) receptor reduces ginsenoside Rb3 neuroprotection in mouse hippocampal slices after oxygen-glucose deprivation. J Ethnopharmacol 2011;133:914-916. https://doi.org/10.1016/j.jep.2010.10.030
  109. Park H, Kim H, Ha E, Yoon S, Kim MJ, Hong M, Leem KH, Hong SJ, Yang J, Chung JH. Panax ginseng increases hypoxia-induced down-regulated cellular response related genes in human neuroblastoma cells, SK-N-MC. Neurol Res 2007;29 Suppl 1:S78-S87.
  110. Si YC, Zhang JP, Xie CE, Zhang LJ, Jiang XN. Effects of Panax notoginseng saponins on proliferation and differentiation of rat hippocampal neural stem cells. Am J Chin Med 2011;39:999-1013. https://doi.org/10.1142/S0192415X11009366
  111. Zhu JR, Tao YF, Lou S, Wu ZM. Protective effects of ginsenoside Rb(3) on oxygen and glucose deprivation-induced ischemic injury in PC12 cells. Acta Pharmacol Sin 2010;31:273-280. https://doi.org/10.1038/aps.2010.9
  112. Siddique MS, Eddeb F, Mantle D, Mendelow AD. Extracts of Ginkgo biloba and Panax ginseng protect brain proteins from free radical induced oxidative damage in vitro. Acta Neurochir Suppl 2000;76:87-90.
  113. Choi SH, Shin TJ, Lee BH, Hwang SH, Lee SM, Lee BC, Park CS, Ha TS, Nah SY. Ginsenoside Rg3 enhances large conductance Ca2+-activated potassium channel currents: a role of Tyr360 residue. Mol Cells 2011;31:133-140. https://doi.org/10.1007/s10059-011-0017-7
  114. Liu D, Li B, Liu Y, Attele AS, Kyle JW, Yuan CS. Voltage-dependent inhibition of brain Na(+) channels by American ginseng. Eur J Pharmacol 2001;413:47-54. https://doi.org/10.1016/S0014-2999(01)00735-X
  115. Jang S, Ryu JH, Kim DH, Oh S. Changes of [3H]MK-801, [3H]muscimol and [3H]flunitrazepam binding in rat brain by the prolonged ventricular infusion of transformed ginsenosides. Neurochem Res 2004;29:2257-2266. https://doi.org/10.1007/s11064-004-7034-2
  116. Wang C, Li YZ, Wang XR, Lu ZR, Shi DZ, Liu XH. Panax quinquefolium saponins reduce myocardial hypoxia-reoxygenation injury by inhibiting excessive endoplasmic reticulum stress. Shock 2012;37:228-233. https://doi.org/10.1097/SHK.0b013e31823f15c4
  117. Chan LS, Yue PY, Mak NK, Wong RN. Role of microRNA-214 in ginsenoside-Rg1-induced angiogenesis. Eur J Pharm Sci 2009;38:370-377. https://doi.org/10.1016/j.ejps.2009.08.008
  118. Yue PY, Wong DY, Ha WY, Fung MC, Mak NK, Yeung HW, Leung HW, Chan K, Liu L, Fan TP et al. Elucidation of the mechanisms underlying the angiogenic effects of ginsenoside Rg(1) in vivo and in vitro. Angiogenesis 2005;8:205-216. https://doi.org/10.1007/s10456-005-9000-2
  119. Chen X, Salwinski S, Lee TJ. Extracts of Ginkgo biloba and ginsenosides exert cerebral vasorelaxation via a nitric oxide pathway. Clin Exp Pharmacol Physiol 1997;24:958-959. https://doi.org/10.1111/j.1440-1681.1997.tb02727.x
  120. Leung KW, Ng HM, Tang MK, Wong CC, Wong RN, Wong AS. Ginsenoside-Rg1 mediates a hypoxia-independent upregulation of hypoxia-inducible factor-$1\alpha$ to promote angiogenesis. Angiogenesis 2011;14:515-522. https://doi.org/10.1007/s10456-011-9235-z
  121. Wang Z, Li M, Wu WK, Tan HM, Geng DF. Ginsenoside Rb1 preconditioning protects against myocardial infarction after regional ischemia and reperfusion by activation of phosphatidylinositol-3-kinase signal transduction. Cardiovasc Drugs Ther 2008;22:443-452. https://doi.org/10.1007/s10557-008-6129-4
  122. Yue QX, Xie FB, Song XY, Wu WY, Jiang BH, Guan SH, Yang M, Liu X, Guo DA. Proteomic studies on protective effects of salvianolic acids, notoginsengnosides and combination of salvianolic acids and notoginsengnosides against cardiac ischemic-reperfusion injury. J Ethnopharmacol 2012;141:659-667. https://doi.org/10.1016/j.jep.2011.08.044
  123. Chen X, Zhou M, Li Q, Yang J, Zhang Y, Zhang D, Kong S, Zhou D, He L. Sanchi for acute ischaemic stroke. Cochrane Database Syst Rev 2008;(4):CD006305.
  124. He L, Chen X, Zhou M, Zhang D, Yang J, Yang M, Zhou D. Radix/rhizome notoginseng extract (sanchitongtshu) for ischemic stroke: a randomized controlled study. Phytomedicine 2011;18:437-442. https://doi.org/10.1016/j.phymed.2010.10.004
  125. Xuejiang W, Magara T, Konishi T. Prevention and repair of cerebral ischemia-reperfusion injury by Chinese herbal medicine, shengmai san, in rats. Free Radic Res 1999;31:449-455. https://doi.org/10.1080/10715769900301011
  126. Zheng M, Qu L, Lou Y. Effects of icariin combined with Panax notoginseng saponins on ischemia reperfusion-induced cognitive impairments related with oxidative stress and CA1 of hippocampal neurons in rat. Phytother Res 2008;22:597-604. https://doi.org/10.1002/ptr.2276
  127. Hartley DE, Elsabagh S, File SE. Gincosan (a combination of Ginkgo biloba and Panax ginseng): the effects on mood and cognition of 6 and 12 weeks’ treatment in post-menopausal women. Nutr Neurosci 2004;7:325-333. https://doi.org/10.1080/10284150400015557
  128. Kuribara H, Tomioka H, Takahashi R, Onozato K, Murohashi N, Numajiri T, Iwata H, Koya S. An antidepressant effect of Sho-ju-sen, a Japanese herbal medicine, assessed by learned helplessness model in mice. Phytother Res 2004;18:173-176. https://doi.org/10.1002/ptr.1412
  129. Dang H, Sun L, Liu X, Peng B, Wang Q, Jia W, Chen Y, Pan A, Xiao P. Preventive action of Kai Xin San aqueous extract on depressive-like symptoms and cognition deficit induced by chronic mild stress. Exp Biol Med (Maywood) 2009;234:785-793. https://doi.org/10.3181/0812-RM-354
  130. Dang H, Chen Y, Liu X, Wang Q, Wang L, Jia W, Wang Y. Antidepressant effects of ginseng total saponins in the forced swimming test and chronic mild stress models of depression. Prog Neuropsychopharmacol Biol Psychiatry 2009;33:1417-1424. https://doi.org/10.1016/j.pnpbp.2009.07.020
  131. Chatterjee M, Verma P, Palit G. Comparative evaluation of Bacopa monniera and Panax quniquefolium in experimental anxiety and depressive models in mice. Indian J Exp Biol 2010;48:306-313.
  132. Kim NH, Kim KY, Jeong HJ, Kim HM. Antidepressant-like effect of altered Korean red ginseng in mice. Behav Med 2011;37:42-46. https://doi.org/10.1080/08964289.2011.566591
  133. Lee B, Kim H, Shim I, Lee H, Hahm DH. Wild ginseng attenuates anxiety- and depression-like behaviors during morphine withdrawal. J Microbiol Biotechnol 2011;21:1088-1096. https://doi.org/10.4014/jmb.1106.06027
  134. Liu L, Luo Y, Zhang R, Guo J. Effects of ginsenosides on hypothalamic-pituitary-adrenal function and brain-derived neurotrophic factor in rats exposed to chronic unpredictable mild stress. Zhongguo Zhong Yao Za Zhi 2011;36:1342-1347.
  135. Wang Z, Dai J, Chen L, Huang Y, Zhao Y. Preventive action of Panax ginseng roots in hypercortisolism-induced Impairment of hippocampal neurons in male C57BL/6N mice. Phytother Res 2011;25:1242-1245. https://doi.org/10.1002/ptr.3389
  136. Yamada N, Araki H, Yoshimura H. Identification of antidepressant-like ingredients in ginseng root (Panax ginseng C.A. Meyer) using a menopausal depressive-like state in female mice: participation of 5-HT2A receptors. Psychopharmacology (Berl) 2011;216:589-599. https://doi.org/10.1007/s00213-011-2252-1
  137. Tode T, Kikuchi Y, Hirata J, Kita T, Nakata H, Nagata I. Effect of Korean red ginseng on psychological functions in patients with severe climacteric syndromes. Int J Gynaecol Obstet 1999;67:169-174. https://doi.org/10.1016/S0020-7292(99)00168-X
  138. Xu C, Teng J, Chen W, Ge Q, Yang Z, Yu C, Yang Z, Jia W. 20(S)-protopanaxadiol, an active ginseng metabolite, exhibits strong antidepressant-like effects in animal tests. Prog Neuropsychopharmacol Biol Psychiatry 2010; 34:1402-1411. https://doi.org/10.1016/j.pnpbp.2010.07.010
  139. Kang A, Hao H, Zheng X, Liang Y, Xie Y, Xie T, Dai C, Zhao Q, Wu X, Xie L et al. Peripheral anti-inflammatory effects explain the ginsenosides paradox between poor brain distribution and anti-depression efficacy. J Neuroinflammation 2011;8:100. https://doi.org/10.1186/1742-2094-8-100
  140. 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
  141. Churchill JD, Gerson JL, Hinton KA, Mifek JL, Walter MJ, Winslow CL, Deyo RA. The nootropic properties of ginseng saponin Rb1 are linked to effects on anxiety. Integr Physiol Behav Sci 2002;37:178-187. https://doi.org/10.1007/BF02734180
  142. 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;28:1621-1625. https://doi.org/10.1248/bpb.28.1621
  143. 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;531:160-165. https://doi.org/10.1016/j.ejphar.2005.12.014
  144. Kim TW, Choi HJ, Kim NJ, Kim DH. Anxiolytic-like effects of ginsenosides Rg3 and Rh2 from red ginseng in the elevated plus-maze model. Planta Med 2009;75:836-839. https://doi.org/10.1055/s-0029-1185402
  145. Wei XY, Yang JY, Wang JH, Wu CF. Anxiolytic effect of saponins from Panax quinquefolium in mice. J Ethnopharmacol 2007;111:613-618. https://doi.org/10.1016/j.jep.2007.01.009
  146. Einat H. Chronic oral administration of ginseng extract results in behavioral change but has no effects in mice models of affective and anxiety disorders. Phytother Res 2007;21:62-66. https://doi.org/10.1002/ptr.2024
  147. Steimer T. Animal models of anxiety disorders in rats and mice: some conceptual issues. Dialogues Clin Neurosci 2011;13:495-506.
  148. Wu CF, Liu YL, Song M, Liu W, Wang JH, Li X, Yang JY. Protective effects of pseudoginsenoside-F11 on methamphetamine-induced neurotoxicity in mice. Pharmacol Biochem Behav 2003;76:103-109. https://doi.org/10.1016/S0091-3057(03)00215-6
  149. Kim SE, Shim I, Chung JK, Lee MC. Effect of ginseng saponins on enhanced dopaminergic transmission and locomotor hyperactivity induced by nicotine. Neuropsychopharmacology 2006;31:1714-1721. https://doi.org/10.1038/sj.npp.1300945
  150. Lee B, Yang CH, Hahm DH, Lee HJ, Han SM, Kim KS, Shim I. Inhibitory effects of ginseng total saponins on behavioral sensitization and dopamine release induced by cocaine. Biol Pharm Bull 2008;31:436-441. https://doi.org/10.1248/bpb.31.436
  151. Nah SY, Bhatia KS, Lyles J, Ellinwood EH, Lee TH. Effects of ginseng saponin on acute cocaine-induced alterations in evoked dopamine release and uptake in rat brain nucleus accumbens. Brain Res 2009;1248:184-190. https://doi.org/10.1016/j.brainres.2008.10.064
  152. Lee B, Kwon S, Yeom M, Shim I, Lee H, Hahm DH. Wild ginseng attenuates repeated morphine-induced behavioral sensitization in rats. J Microbiol Biotechnol 2011;21:757-765. https://doi.org/10.4014/jmb.1103.03016
  153. Gupta YK, Sharma M, Chaudhary G. Antiepileptic activity of Panax ginseng against pentylenetetrazole induced kindling in rats. Indian J Physiol Pharmacol 2001;45:502-506.
  154. Kim S, Rhim H. Ginsenosides inhibit NMDA receptor-mediated epileptic discharges in cultured hippocampal neurons. Arch Pharm Res 2004;27:524-530. https://doi.org/10.1007/BF02980126
  155. Lian XY, Zhang ZZ, Stringer JL. Anticonvulsant activity of ginseng on seizures induced by chemical convulsants. Epilepsia 2005;46:15-22.
  156. Lian XY, Zhang Z, Stringer JL. Anticonvulsant and neuroprotective effects of ginsenosides in rats. Epilepsy Res 2006;70:244-256. https://doi.org/10.1016/j.eplepsyres.2006.05.010
  157. Chen EY, Hui CL. HT1001, a proprietary North American ginseng extract, improves working memory in schizophrenia: a double-blind, placebo-controlled study. Phytother Res 2012;26:1166-1172. https://doi.org/10.1002/ptr.3700
  158. Chatterjee M, Singh S, Kumari R, Verma AK, Palit G. Evaluation of the antipsychotic potential of Panax quinquefolium in ketamine induced experimental psychosis model in mice. Neurochem Res 2012;37:759-770. https://doi.org/10.1007/s11064-011-0670-4
  159. Lyon MR, Cline JC, Totosy de Zepetnek J, Shan JJ, Pang P, Benishin C. Effect of the herbal extract combination Panax quinquefolium and Ginkgo biloba on attention-deficit hyperactivity disorder: a pilot study. J Psychiatry Neurosci 2001;26:221-228.
  160. Niederhofer H. Panax ginseng may improve some symptoms of attention-deficit hyperactivity disorder. J Diet Suppl 2009;6:22-27. https://doi.org/10.1080/19390210802687221
  161. Russell VA. Overview of animal models of attention deficit hyperactivity disorder (ADHD). Curr Protoc Neurosci 2011;Chapter 9:Unit9.35.
  162. Niederhofer H. First preliminary results of an observation of Panax ginseng treatment in patients with autistic disorder. J Diet Suppl 2009;6:342-346. https://doi.org/10.3109/19390210903280231
  163. Wang J, Flaisher-Grinberg S, Li S, Liu H, Sun L, Zhou Y, Einat H. Antidepressant-like effects of the active acidic polysaccharide portion of ginseng in mice. J Ethnopharmacol 2010;132:65-69. https://doi.org/10.1016/j.jep.2010.07.042

피인용 문헌

  1. Ginsenoside Rg-1 Protects Retinal Pigment Epithelium (RPE) Cells from Cobalt Chloride (CoCl2) and Hypoxia Assaults vol.8, pp.12, 2013, https://doi.org/10.1371/journal.pone.0084171
  2. Ginsenoside Rb1 Protects Rat Neural Progenitor Cells against Oxidative Injury vol.19, pp.3, 2014, https://doi.org/10.3390/molecules19033012
  3. Evaluation of Four Different Analytical Tools to Determine the Regional Origin of Gastrodia elata and Rehmannia glutinosa on the Basis of Metabolomics Study vol.19, pp.5, 2014, https://doi.org/10.3390/molecules19056294
  4. Ginsenosides Rb1 and Rg1 Stimulate Melanogenesis in Human Epidermal Melanocytes via PKA/CREB/MITF Signaling vol.2014, pp.1741-4288, 2014, https://doi.org/10.1155/2014/892073
  5. by FT-NIR Spectroscopy vol.2014, pp.2090-8873, 2014, https://doi.org/10.1155/2014/741571
  6. A dual purpose cell line of an Indian congener of ginseng—Panax sikkimensis with distinct ginsenoside and anthocyanin production profiles vol.252, pp.2, 2015, https://doi.org/10.1007/s00709-014-0695-z
  7. Caspase-mediated Apoptotic Effects of Diol-type Ginseng Sapogenins on Human Hepatoma Cell Lines vol.36, pp.1, 2015, https://doi.org/10.1002/bkcs.10074
  8. on driving performance vol.53, pp.2, 2015, https://doi.org/10.3109/15563650.2014.999159
  9. GABA-BZD Receptor Modulating Mechanism of Panax quinquefolius against 72-h Sleep Deprivation Induced Anxiety like Behavior: Possible Roles of Oxidative Stress, Mitochondrial Dysfunction and Neuroinflammation vol.10, pp.1662-453X, 2016, https://doi.org/10.3389/fnins.2016.00084
  10. TCM, brain function and drug space vol.33, pp.1, 2016, https://doi.org/10.1039/C5NP00049A
  11. /HRMS vol.40, pp.11, 2016, https://doi.org/10.1039/C6NJ01702A
  12. Ginsenoside Rg1 reverses stress-induced depression-like behaviours and brain-derived neurotrophic factor expression within the prefrontal cortex vol.44, pp.2, 2016, https://doi.org/10.1111/ejn.13255
  13. Korean Red Ginseng and Ginsenoside-Rb1/-Rg1 Alleviate Experimental Autoimmune Encephalomyelitis by Suppressing Th1 and Th17 Cells and Upregulating Regulatory T Cells vol.53, pp.3, 2016, https://doi.org/10.1007/s12035-015-9131-4
  14. Compound K derived from ginseng: neuroprotection and cognitive improvement vol.7, pp.11, 2016, https://doi.org/10.1039/C6FO01077F
  15. Pretreatment with Ginseng Fruit Saponins Affects Serotonin Expression in an Experimental Comorbidity Model of Myocardial Infarction and Depression vol.7, pp.6, 2016, https://doi.org/10.14336/AD.2016.0729
  16. Ginsenoside Rb1 rescues anxiety-like responses in a rat model of post-traumatic stress disorder vol.70, pp.2, 2016, https://doi.org/10.1007/s11418-015-0943-3
  17. A literature update elucidating production of Panax ginsenosides with a special focus on strategies enriching the anti-neoplastic minor ginsenosides in ginseng preparations vol.101, pp.10, 2017, https://doi.org/10.1007/s00253-017-8279-4
  18. Effects of medicinal plants on Alzheimer's disease and memory deficits vol.12, pp.4, 2017, https://doi.org/10.4103/1673-5374.205108
  19. Ginsenoside Rg1 Ameliorates Behavioral Abnormalities and Modulates the Hippocampal Proteomic Change in Triple Transgenic Mice of Alzheimer’s Disease vol.2017, pp.1942-0994, 2017, https://doi.org/10.1155/2017/6473506
  20. A Preclinical Systematic Review of Ginsenoside-Rg1 in Experimental Parkinson’s Disease vol.2017, pp.1942-0994, 2017, https://doi.org/10.1155/2017/2163053
  21. Anti-wrinkle effect of fermented black ginseng on human fibroblasts vol.39, pp.3, 2017, https://doi.org/10.3892/ijmm.2017.2858
  22. Pharmacokinetic Drug Interactions with Panax ginseng vol.42, pp.4, 2017, https://doi.org/10.1007/s13318-016-0387-5
  23. Acupuncture plus Herbal Medicine for Alzheimer’s Disease: A Systematic Review and Meta-Analysis vol.45, pp.07, 2017, https://doi.org/10.1142/S0192415X17500732
  24. Ginsenoside Rk1 bioactivity: a systematic review vol.5, pp.2167-8359, 2017, https://doi.org/10.7717/peerj.3993
  25. Ginsenoside Rd as a potential neuroprotective agent prevents trimethyltin injury vol.6, pp.4, 2017, https://doi.org/10.3892/br.2017.864
  26. Evaluation of structure–activity relationships of ginsenosides against amyloid β induced pathological behaviours in transgenic Caenorhabditis elegans vol.7, pp.64, 2017, https://doi.org/10.1039/C7RA05717B
  27. Ginseng Extract G115 Attenuates Ethanol-Induced Depression in Mice by Increasing Brain BDNF Levels vol.9, pp.9, 2017, https://doi.org/10.3390/nu9090931
  28. Inhibition of Autophagy is Involved in the Protective Effects of Ginsenoside Rb1 on Spinal Cord Injury pp.1573-6830, 2017, https://doi.org/10.1007/s10571-017-0527-8
  29. Antioxidative Dietary Compounds Modulate Gene Expression Associated with Apoptosis, DNA Repair, Inhibition of Cell Proliferation and Migration vol.15, pp.9, 2014, https://doi.org/10.3390/ijms150916226
  30. Dietary Supplementation of Chinese Ginseng Prevents Obesity and Metabolic Syndrome in High-Fat Diet-Fed Mice vol.17, pp.12, 2014, https://doi.org/10.1089/jmf.2014.0016
  31. Mountain-Cultivated Ginseng Attenuates Phencyclidine-Induced Abnormal Behaviors in Mice by Positive Modulation of Glutathione in the Prefrontal Cortex of Mice vol.19, pp.10, 2016, https://doi.org/10.1089/jmf.2016.3751
  32. Neurogenic Traditional Chinese Medicine as a Promising Strategy for the Treatment of Alzheimer’s Disease vol.18, pp.2, 2017, https://doi.org/10.3390/ijms18020272
  33. Korean Red Ginseng Pretreatment Protects Against Long-Term Sensorimotor Deficits After Ischemic Stroke Likely Through Nrf2 vol.12, pp.1662-5102, 2018, https://doi.org/10.3389/fncel.2018.00074
  34. Effect and Safety of Huannao Yicong Formula (还脑益聪方) on Patients with Mild-to-Moderate Alzheimer’s Disease: A Randomized, Double-Blinded, Donepezil-Controlled Trial pp.1993-0402, 2019, https://doi.org/10.1007/s11655-018-3054-7
  35. Gintonin, a Ginseng-Derived Exogenous Lysophosphatidic Acid Receptor Ligand, Protects Astrocytes from Hypoxic and Re-oxygenation Stresses Through Stimulation of Astrocytic Glycogenolysis pp.1559-1182, 2019, https://doi.org/10.1007/s12035-018-1308-1
  36. Synergistic effect of Korean red ginseng and Pueraria montana var. lobata against trimethyltin-induced cognitive impairment vol.27, pp.4, 2018, https://doi.org/10.1007/s10068-018-0362-9
  37. Effects of 60Co-γ and Electron Beam Irradiation on Storage Quality of Panax ginseng vol.11, pp.9, 2018, https://doi.org/10.1007/s11947-018-2108-3
  38. A Combination of Essential Fatty Acids, Panax Ginseng Extract, and Green Tea Catechins Modifies Brain fMRI Signals in Healthy Older Adults vol.22, pp.7, 2018, https://doi.org/10.1007/s12603-018-1028-2
  39. and their improved bioactivities vol.34, pp.7, 2018, https://doi.org/10.1080/87559129.2018.1424183
  40. and its constituents, ginsenosides and gintonin, in neurological and neurodegenerative disorders: a patent review vol.29, pp.1, 2019, https://doi.org/10.1080/13543776.2019.1556258
  41. Ginsenoside Rf relieves mechanical hypersensitivity, depression-like behavior, and inflammatory reactions in chronic constriction injury rats pp.0951418X, 2019, https://doi.org/10.1002/ptr.6303
  42. Ginseng: a promising neuroprotective strategy in stroke vol.8, pp.None, 2014, https://doi.org/10.3389/fncel.2014.00457
  43. The Dietary Flavonoid Kaempferol Mediates Anti-Inflammatory Responses via the Src, Syk, IRAK1, and IRAK4 Molecular Targets vol.2015, pp.None, 2013, https://doi.org/10.1155/2015/904142
  44. Red ginseng represses hypoxia-induced cyclooxygenase-2 through sirtuin1 activation vol.22, pp.6, 2015, https://doi.org/10.1016/j.phymed.2015.03.005
  45. Pharmacological Effects of Active Components of Chinese Herbal Medicine in the Treatment of Alzheimer's Disease: A Review vol.44, pp.8, 2013, https://doi.org/10.1142/s0192415x16500853
  46. Supplementation of Korean Red Ginseng improves behavior deviations in animal models of autism vol.60, pp.None, 2013, https://doi.org/10.3402/fnr.v60.29245
  47. 흰 쥐의 턱관절 염증성 통증모델에서 홍삼 및 흑삼추출물의 효과 vol.17, pp.1, 2017, https://doi.org/10.17135/jdhs.2017.17.1.65
  48. Bioconversion Using Lactic Acid Bacteria: Ginsenosides, GABA, and Phenolic Compounds vol.27, pp.5, 2013, https://doi.org/10.4014/jmb.1612.12005
  49. Inhibition of hypoxia-induced cyclooxygenase-2 by Korean Red Ginseng is dependent on peroxisome proliferator-activated receptor gamma vol.41, pp.3, 2013, https://doi.org/10.1016/j.jgr.2016.04.001
  50. Phytoconstituents and Biological Activities of Panax vietnamensis (Vietnamese Ginseng): A Precious Ginseng and Call for Further Research-A systematic review vol.13, pp.10, 2013, https://doi.org/10.1177/1934578x1801301036
  51. Effects of Panax ginseng C.A. Meyer extract on the offspring of adult mice with maternal immune activation vol.18, pp.4, 2013, https://doi.org/10.3892/mmr.2018.9417
  52. Complete Biotransformation of Protopanaxatriol-Type Ginsenosides in Panax ginseng Leaf Extract to Aglycon Protopanaxatriol by β-Glycosidases from Dictyoglomus turgidum and Pyrococcus furiosus vol.28, pp.2, 2013, https://doi.org/10.4014/jmb.1709.09053
  53. Active ginseng components in cognitive impairment: Therapeutic potential and prospects for delivery and clinical study vol.9, pp.71, 2018, https://doi.org/10.18632/oncotarget.26035
  54. Jia-Wei-Kai-Xin-San, an Herbal Medicine Formula, Ameliorates Cognitive Deficits via Modulating Metabolism of Beta Amyloid Protein and Neurotrophic Factors in Hippocampus of Aβ 1-42 In vol.10, pp.None, 2019, https://doi.org/10.3389/fphar.2019.00258
  55. Herbal Compatibility of Ginseng and Rhubarb Exerts Synergistic Neuroprotection in Cerebral Ischemia/Reperfusion Injury of Rats vol.10, pp.None, 2019, https://doi.org/10.3389/fphys.2019.01174
  56. Ginsenoside Compound K Regulates Amyloid β via the Nrf2/Keap1 Signaling Pathway in Mice with Scopolamine Hydrobromide-Induced Memory Impairments vol.67, pp.1, 2013, https://doi.org/10.1007/s12031-018-1210-3
  57. Integrated Metabolomics and Network Pharmacology Study on Immunoregulation Mechanisms ofPanax ginsengthrough Macrophages vol.2019, pp.None, 2019, https://doi.org/10.1155/2019/3630260
  58. Effects of Ginsenoside Rg1 Regulating Wnt/ β -Catenin Signaling on Neural Stem Cells to Delay Brain Senescence vol.2019, pp.None, 2019, https://doi.org/10.1155/2019/5010184
  59. Biotransformation of Glycoginsenosides to Intermediate Products and Aglycones using a Hemicellulosome Produced by Cellulosimicrobium cellulan vol.55, pp.2, 2019, https://doi.org/10.1134/s0003683819020054
  60. The Chinese Herbal Formula PAPZ Ameliorates Behavioral Abnormalities in Depressive Mice vol.11, pp.4, 2019, https://doi.org/10.3390/nu11040859
  61. Black Ginseng and Its Saponins: Preparation, Phytochemistry and Pharmacological Effects vol.24, pp.10, 2013, https://doi.org/10.3390/molecules24101856
  62. Neuroprotective Effects of Red Ginseng Saponins in Scopolamine-Treated Rats and Activity Screening Based on Pharmacokinetics vol.24, pp.11, 2013, https://doi.org/10.3390/molecules24112136
  63. Ginsenoside Re Inhibits ROS/ASK-1 Dependent Mitochondrial Apoptosis Pathway and Activation of Nrf2-Antioxidant Response in Beta-Amyloid-Challenged SH-SY5Y Cells vol.24, pp.15, 2013, https://doi.org/10.3390/molecules24152687
  64. Supplementation of Plants with Immunomodulatory Properties during Pregnancy and Lactation-Maternal and Offspring Health Effects vol.11, pp.8, 2013, https://doi.org/10.3390/nu11081958
  65. Management of oxidative stress and other pathologies in Alzheimer’s disease vol.93, pp.9, 2013, https://doi.org/10.1007/s00204-019-02538-y
  66. Transcriptomic profiling reveals MEP pathway contributing to ginsenoside biosynthesis in Panax ginseng vol.20, pp.None, 2019, https://doi.org/10.1186/s12864-019-5718-x
  67. Frondoside A Attenuates Amyloid-β Proteotoxicity in Transgenic Caenorhabditis elegans by Suppressing Its Formation vol.11, pp.None, 2013, https://doi.org/10.3389/fphar.2020.553579
  68. Effect of Omega-3 and Korean Red Ginseng on Children with Attention Deficit Hyperactivity Disorder: An Open-Label Pilot Study vol.18, pp.1, 2020, https://doi.org/10.9758/cpn.2020.18.1.75
  69. Characterization and Antioxidant Activity Determination of Neutral and Acidic Polysaccharides from Panax Ginseng C. A. Meyer vol.25, pp.4, 2013, https://doi.org/10.3390/molecules25040791
  70. Gintonin-Enriched Fraction Suppresses Heat Stress-Induced Inflammation through LPA Receptor vol.25, pp.5, 2013, https://doi.org/10.3390/molecules25051019
  71. Characteristics of Panax ginseng Cultivars in Korea and China vol.25, pp.11, 2013, https://doi.org/10.3390/molecules25112635
  72. Physiological responses and ginsenoside production of Panax ginseng seedlings grown under various ratios of red to blue light-emitting diodes vol.61, pp.4, 2013, https://doi.org/10.1007/s13580-020-00255-5
  73. Protective effect of ginsenoside rd on lipopolysaccharide-induced acute lung injury through its anti-inflammatory and anti-oxidative activity vol.7, pp.3, 2013, https://doi.org/10.4103/wjtcm.wjtcm_12_21
  74. Protective Effects and Mechanism of Radix Polygalae Against Neurological Diseases as Well as Effective Substance vol.12, pp.None, 2013, https://doi.org/10.3389/fpsyt.2021.688703
  75. Impacts of Drug Interactions on Pharmacokinetics and the Brain Transporters: A Recent Review of Natural Compound-Drug Interactions in Brain Disorders vol.22, pp.4, 2021, https://doi.org/10.3390/ijms22041809
  76. Protective Effects of Gynostemma pentaphyllum (var. Ginpent) against Lipopolysaccharide-Induced Inflammation and Motor Alteration in Mice vol.26, pp.3, 2013, https://doi.org/10.3390/molecules26030570
  77. Ginsenoside Rb1 attenuates microglia activation to improve spinal cord injury via microRNA‐130b‐5p/TLR4/NF‐κB axis vol.236, pp.3, 2013, https://doi.org/10.1002/jcp.30001
  78. Mesenchymal stem cell therapies for Alzheimer’s disease: preclinical studies vol.36, pp.7, 2013, https://doi.org/10.1007/s11011-021-00777-6
  79. In vitro modulatory effects of ginsenoside compound K, 20(S)-protopanaxadiol and 20(S)-protopanaxatriol on uridine 5′-diphospho-glucuronosyltransferase activity and expression vol.51, pp.10, 2013, https://doi.org/10.1080/00498254.2021.1963503
  80. New and known phenylpropanoid glycosides from mountain cultivated ginseng vol.35, pp.21, 2013, https://doi.org/10.1080/14786419.2020.1753051
  81. Efficacy of Omega-3 and Korean Red Ginseng in Children with Subthreshold ADHD: A Double-Blind, Randomized, Placebo-Controlled Trial vol.25, pp.14, 2013, https://doi.org/10.1177/1087054720951868
  82. Korean Red Ginseng Improves Astrocytic Mitochondrial Function by Upregulating HO-1-Mediated AMPKα-PGC-1α-ERRα Circuit after Traumatic Brain Injury vol.22, pp.23, 2013, https://doi.org/10.3390/ijms222313081
  83. Ginsenoside Compound K Assisted G-Quadruplex Folding and Regulated G-Quadruplex-Containing Transcription vol.26, pp.23, 2013, https://doi.org/10.3390/molecules26237339