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Prolonged oral administration of Gastrodia elata extract improves spatial learning and memory of scopolamine-treated rats


Gastrodia elata (GE) is traditionally used for treatment of various disorders including neurodegenerative diseases such as Alzheimer’s disease. To investigate the neuroprotective effect of GE, amyloid-β peptide (Aβ)-treated PC12 cells were cultured with GE aqueous extract. In vitro assay demonstrated that 50 µM of pre-aggregated Aβ was lethal to about a half portion of PC12 cells and that Aβ aggregate-induced cell death was significantly decreased with GE treatment at ≤10 mg/mL in a dose-dependent manner. To further examine in vivo cognitive-improving effects, an artificial amnesic animal model, scopolamineinjected Sprague-Dawley rats, were orally administered the extract for 6 weeks followed by behavioral tests (the passive avoidance test and Morris water maze test). The results showed that an acute treatment with scopolamine (1 mg/kg of body weight) effectively induced memory impairment in normal rats and that the learning and memory capability of scopolamine-treated rats improved after prolonged administration of GE extract (50, 250 and 500 mg/kg of body weight for 6 weeks). These findings suggest that a GE regimen may potentially ameliorate learning and memory deficits and/or cognitive impairments caused by neuronal cell death.


  1. 1.

    Querfurth HW, LaFerla FM. Alzheimer’s disease. N Engl J Med 2010; 362(4): 329–344.

    CAS  Article  Google Scholar 

  2. 2.

    Tanzi RE, Bertram L. Twenty years of the Alzheimer’s disease amyloid hypothesis: a genetic perspective. Cell 2005; 120(4): 545–555.

    CAS  Article  Google Scholar 

  3. 3.

    Green KN, Billings LM, Roozendaal B, McGaugh JL, LaFerla FM. Glucocorticoids increase amyloid-beta and tau pathology in a mouse model of Alzheimer’s disease. J Neurosci 2006; 26(35): 9047–9056.

    CAS  Article  Google Scholar 

  4. 4.

    Ojemann LM, Nelson WL, Shin DS, Rowe AO, Buchanan RA. Tian ma, an ancient Chinese herb, offers new options for the treatment of epilepsy and other conditions. Epilepsy Behav 2006; 8(2): 376–383.

    Article  Google Scholar 

  5. 5.

    Hsieh CL, Tang NY, Chiang SY, Hsieh CT, Lin JG. Anticonvulsive and free radical scavenging actions of two herbs, Uncaria rhynchophylla (MIQ) Jack and Gastrodia elata Bl., in kainic acid-treated rats. Life Sci 1999; 65(20): 2071–2082.

    CAS  Article  Google Scholar 

  6. 6.

    Zhu L, Guan H, Cui C, Tian S, Yang D, Wang X, Zhang S, Wang L, Jiang H. Gastrodin inhibits cell proliferation in vascular smooth muscle cells and attenuates neointima formation in vivo. Int J Mol Med 2012; 30(3): 1034–1040.

    CAS  Article  Google Scholar 

  7. 7.

    Shu C, Chen C, Zhang DP, Guo H, Zhou H, Zong J, Bian Z, Dong X, Dai J, Zhang Y, Tang Q. Gastrodin protects against cardiac hypertrophy and fibrosis. Mol Cell Biochem 2012; 359(1-2): 9–16.

    CAS  Article  Google Scholar 

  8. 8.

    Ha JH, Shin SM, Lee SK, Kim JS, Shin US, Huh K, Kim JA, Yong CS, Lee NJ, Lee DU. In vitro effects of hydroxybenzaldehydes from Gastrodia elata and their analogues on GABAergic neurotransmission, and a structure-activity correlation. Planta Med 2001; 67(3): 877–880.

    CAS  Article  Google Scholar 

  9. 9.

    Ha JH, Lee DU, Lee JT, Kim JS, Yong CS, Kim JA, Ha JS, Huh K. 4-Hydroxybenzaldehyde from Gastrodia elata B1. is active in the antioxidation and GABAergic neuromodulation of the rat brain. J Ethnopharmacol 2000; 73(1-2): 329–333.

    CAS  Article  Google Scholar 

  10. 10.

    Mishra M, Huang J, Lee YY, Chua DS, Lin X, Hu JM, Heese K. Gastrodia elata modulates amyloid precursor protein cleavage and cognitive functions in mice. Biosci Trends 2011; 5(2): 129–138.

    Article  Google Scholar 

  11. 11.

    Manavalan A, Ramachandran U, Sundaramurthi H, Mishra M, Sze SK, Hu JM, Feng ZW, Heese K. Gastrodia elata Blume (tianma) mobilizes neuro-protective capacities. Int J Biochem Mol Biol 2012; 3(2): 219–241.

    PubMed  PubMed Central  Google Scholar 

  12. 12.

    Phillips RG, LeDoux JE. Lesions of the fornix but not the entorhinal or perirhinal cortex interfere with contextual fear conditioning. J Neurosci 1995; 15(7 Pt 2): 5308–5315.

    CAS  Article  Google Scholar 

  13. 13.

    Bayer TA, Wirths O, Majtényi K, Hartmann T, Multhaup G, Beyreuther K, Czech C. Key factors in Alzheimer’s disease: betaamyloid precursor protein processing, metabolism and intraneuronal transport. Brain Pathol 2001; 11(3): 1–11.

    CAS  PubMed  Google Scholar 

  14. 14.

    Liu P, Jing Y, Collie ND, Campbell SA, Zhang H. Pre-aggregated Lab Anim Resin the rat hippocampus and prefrontal cortex. Neuroscience 2011; 193: 269–282.

    CAS  Article  Google Scholar 

  15. 15.

    Ng CF, Ko CH, Koon CM, Xian JW, Leung PC, Fung KP, Chan HY, Lau CB. The Aqueous Extract of Rhizome of Gastrodia elata Protected Drosophila and PC12 Cells against Beta-Amyloid- Induced Neurotoxicity. Evid Based Complement Alternat Med 2013; 2013: 516741.

  16. 16.

    Wesnes KA, Simpson PM, White L, Pinker S, Jertz G, Murphy M, Siegfried K. Cholinesterase inhibition in the scopolamine model of dementia. Ann N Y Acad Sci 1991; 640: 268–271.

    CAS  Article  Google Scholar 

  17. 17.

    Deutsch JA. The cholinergic synapse and the site of memory. Science 1971; 174(4011): 788–794.

    CAS  Article  Google Scholar 

  18. 18.

    Ebert U, Kirch W. Scopolamine model of dementia: electroencephalogram findings and cognitive performance. Eur J Clin Invest 1998; 28(11): 944–949.

    CAS  Article  Google Scholar 

  19. 19.

    Bartus RT, Dean RL 3rd, Beer B, Lippa AS. The cholinergic hypothesis of geriatric memory dysfunction. Science 1982; 217(4558): 408–414.

    Google Scholar 

  20. 20.

    Izquierdo I. Mechanism of action of scopolamine as an amnestic. Trends Pharmacol Sci 1989; 10(3): 175–177.

    CAS  Article  Google Scholar 

  21. 21.

    Wu CR, Hsieh MT, Huang SC, Peng WH, Chang YS, Chen CF. Effects of Gastrodia elata and its active constituents on scopolamine-induced amnesia in rats. Planta Med 1996; 62(3): 317–321.

    CAS  Article  Google Scholar 

  22. 22.

    Hsieh MT, Wu CR, Chen CF. Gastrodin and p-hydroxybenzyl alcohol facilitate memory consolidation and retrieval, but not acquisition, on the passive avoidance task in rats. J Ethnopharmacol 1997; 56(3): 45–54.

    CAS  Article  Google Scholar 

  23. 23.

    Kim HJ, Moon KD, Oh SY, Kim SP, Lee SR. Ether fraction of methanol extracts of Gastrodia elata, a traditional medicinal herb, protects against kainic acid-induced neuronal damage in the mouse hippocampus. Neurosci Lett 2001; 314(1-2): 65–68.

    Google Scholar 

  24. 24.

    An SJ, Park SK, Hwang IK, Choi SY, Kim SK, Kwon OS, Jung SJ, Baek NI, Lee HY, Won MH, Kang TC. Gastrodin decreases immunoreactivities of gamma-aminobutyric acid shunt enzymes in the hippocampus of seizure-sensitive gerbils. J Neurosci Res 2003; 71(3): 534–543.

    CAS  Article  Google Scholar 

  25. 25.

    Zeng X, Zhang S, Zhang L, Zhang K, Zheng X. A study of the neuroprotective effect of the phenolic glucoside gastrodin during cerebral ischemia in vivo and in vitro. Planta Med 2006; 72(15): 1359–1365.

    CAS  Article  Google Scholar 

  26. 26.

    Dai JN, Zong Y, Zhong LM, Li YM, Zhang W, Bian LG, Ai QL, Liu YD, Sun J, Lu D. Gastrodin inhibits expression of inducible NO synthase, cyclooxygenase-2 and proinflammatory cytokines in cultured LPS-stimulated microglia via MAPK pathways. PLoS One 2011; 6(2): e21891.

    Google Scholar 

  27. 27.

    Zhao X, Zou Y, Xu H, Fan L, Guo H, Li X, Li G, Zhang X, Dong M. Gastrodin protect primary cultured rat hippocampal neurons against amyloid-beta peptide-induced neurotoxicity via ERK1/2-Nrf2 pathway. Brain Res 2012; 1482: 13–21.

    CAS  Article  Google Scholar 

  28. 28.

    Kumar H, Kim IS, More SV, Kim BW, Bahk YY, Choi DK. Gastrodin protects apoptotic dopaminergic neurons in a toxininduced Parkinson’s disease model. Evid Based Complement Alternat Med 2013; 2013: 514095.

  29. 29.

    Wang Q, Chen G, Zeng S. Distribution and metabolism of gastrodin in rat brain. J Pharm Biomed Anal 2008; 46(3): 399- 404.

    Google Scholar 

  30. 30.

    Wang Q, Chen G, Zeng S. Pharmacokinetics of Gastrodin in rat plasma and CSF after i.n. and i.v. Int J Pharm 2007; 341(1-2): 20- 25.

    Google Scholar 

  31. 31.

    Lin LC, Chen YF, Tsai TR, Tsai TH. Analysis of brain distribution and biliary excretion of a nutrient supplement, gastrodin, in rat. Anal Chim Acta 2007; 590(4): 173–179.

    CAS  Article  Google Scholar 

  32. 32.

    Lin LC, Chen YF, Lee WC, Wu YT, Tsai TH. Pharmacokinetics of gastrodin and its metabolite p-hydroxybenzyl alcohol in rat blood, brain and bile by microdialysis coupled to LC-MS/MS. J Pharm Biomed Anal 2008; 48(3): 909–917.

    CAS  Article  Google Scholar 

  33. 33.

    Zheng Q, Yue PF, Wu B, Hu PY, Wu ZF, Yang M. Pharmacokinetics comparative study of a novel Chinese traditional herbal formula and its compatibility. J Ethnopharmacol 2011; 137(4): 221–225.

    Article  Google Scholar 

  34. 34.

    Jiang L, Dai J, Huang Z, Du Q, Lin J, Wang Y. Simultaneous determination of gastrodin and puerarin in rat plasma by HPLC and the application to their interaction on pharmacokinetics. J Chromatogr B Analyt Technol Biomed Life Sci 2013; 915–916: 8–12.

    Google Scholar 

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This study was supported by the Core Technology Development and Commercialization Support in Industry-Academia-Research Collaboration (project no. 2013C03) funded by the province of Jeonbuk, Korea.

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Correspondence to Jisun Oh or Hak-Yong Lee.

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Park, YM., Lee, BG., Park, SH. et al. Prolonged oral administration of Gastrodia elata extract improves spatial learning and memory of scopolamine-treated rats. Lab Anim Res 31, 69–77 (2015).

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  • Gastrodia elata
  • scopolamine-induced memory impairment
  • amyloid-β peptide
  • neuroprotective effect
  • cognitive-enhancing effect