Abstract
The phenolic glucoside gastrodin is the main component extracted from the rhizome
of Gastrodia elata (Orchidaceae), a Chinese herbal medicine, which has long been used for treating dizziness,
epilepsy, stroke and dementia. The present study aims to investigate the effect of
gastrodin on hypoxia-induced neurotoxicity in cultured rat cortical neurons. Neuron
survival and extracellular glutamate level were measured after an insult by hypoxia.
Glutamate concentrations were determined by an HPLC-ECD system. The results demonstrated
that neurons were significantly damaged by hypoxia for 24 h. When pretreated with
gastrodin (100, 200 μg/mL) in hypoxia, neuron survival was significantly increased
compared with no gastrodin treatment. Moreover, the enhancement of extracellular glutamate
level stimulated by hypoxia was inhibited by pretreatment with gastrodin (100 μg/mL).
Further studies demonstrated that gastrodin prevented glutamate- and NMDA-induced
neurotoxicity. In addition, gastrodin also inhibited the extracellular glutamate level
induced by NMDA insult. These findings suggest that gastrodin has a neuroprotective
action against hypoxia in the cultured cortical neuron, and the mechanism may involve
a decreasing of the extracellular glutamate level.
Abbreviations
GABA:γ-aminobutyric acid
DMEM:Dulbecco's modified Eagle's medium
MTT:3-(4,5)-dimethylthiathiazo(-z-yl)-3,5-di-phenytetrazoliumromide
HPLC-ECD:high performance liquid chromatography with
electrochemical detection
Key words
Gastrodin - hypoxia - neuroprotection - glutamate - NMDA -
Gastrodia elata
- Orchidaceae
References
- 1
Roach R C, Hackett P H.
Frontiers of hypoxia research: acute mountain sickness.
J Exp Biol.
2001;
204
3161-70.
- 2
Lee J M, Zipfel G J, Choi D W.
The changing landscape of ischaemic brain injury mechanisms.
Nature.
1999;
399
A7-14.
- 3
Johnston M V.
Excitotoxicity in neonatal hypoxia.
Ment Retard Dev Disabil Res Rev.
2001;
7
229-34.
- 4
Huang J H.
Comparison studies on pharmacological properties of injectio gastrodia elata, gastrodin-free
fraction and gastrodin.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao.
1989;
11
147-50.
- 5
Baek N I, Choi S Y, Park J K, Cho S W, Ahn E M, Jeon S G. et al .
Isolation and identification of succinic semialdehyde dehydrogenase inhibitory compound
from the rhizome of Gastrodia elata Blume.
Arch Pharm Res.
1999;
22
219-24.
- 6
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
1359-65.
- 7
An S J, Park S K, Hwang I K, Choi S Y, Kim S K, Kwon O S. et al .
Gastrodin decreases immunoreactivities of gamma-aminobutyric acid shunt enzymes in
the hippocampus of seizure-sensitive gerbils.
J Neurosci Res.
2003;
71
534-43.
- 8
Liu Y, Tang X, Pei J, Zhang L, Liu F, Li K.
Gastrodin interaction with human fibrinogen: anticoagulant effects and binding studies.
Chemistry.
2006;
12
7807-15.
- 9
Cheung N S, Pascoe C J, Giardina S F, John C A, Beart P M.
Micromolar l-glutamate induces extensive apoptosis in an apoptotic-necrotic continuum
of insult-dependent, excitotoxic injury in cultured cortical neurones.
Neuropharmacology.
1998;
37
1419-29.
- 10
Donzanti B A, Yamamoto B K.
An improved and rapid HPLC-EC method for the isocratic separation of amino acid neurotransmitters
from brain tissue and microdialysis perfusates.
Life Sci.
1988;
43
913-22.
- 11
Kiang J G, Tsen K T.
Biology of hypoxia.
Chin J Physiol.
2006;
49
223-33.
- 12
Arundine M, Tymianski M.
Molecular mechanisms of glutamate-dependent neurodegeneration in ischemia and traumatic
brain injury.
Cell Mol Life Sci.
2004;
61
657-68.
- 13
Tan W K, Williams C E, During M J, Mallard C E, Gunning M I, Gunn A J. et al .
Accumulation of cytotoxins during the development of seizures and edema after hypoxic-ischemic
injury in late gestation fetal sheep.
Pediatr Res.
1996;
39
791-7.
- 14
Weinberger J M.
Evolving therapeutic approaches to treating acute ischemic stroke.
J Neurol Sci.
2006;
249
101-9.
- 15
Park J H, Lee H J, Koh S B, Ban J Y, Seong Y H.
Protection of NMDA-induced neuronal cell damage by methanol extract of Zizyphi spinosi semen in cultured rat cerebellar granule cells.
J Ethnopharmacol.
2004;
95
39-45.
- 16
Sugawara T, Fujimura M, Noshita N, Kim G W, Saito A, Hayashi T. et al .
Neuronal death/survival signaling pathways in cerebral ischemia.
NeuroRx.
2004;
1
17-25.
- 17
Hertz L.
Glutamate, a neurotransmitter - and so much more. A synopsis of Wierzba III.
Neurochem Int.
2006;
48
416-25.
- 18
Hagberg H, Andersson P, Kjellmer I, Thiringer K, Thordstein M.
Extracellular overflow of glutamate, aspartate, GABA and taurine in the cortex and
basal ganglia of fetal lambs during hypoxia-ischemia.
Neurosci Lett.
1987;
78
311-7.
Xiaodong Bie
Department of Traditional Chinese Medicine
Second Affiliated Hospital
School of Medicine
Zhejiang University
Hangzhou 310009
People's Republic of China
Telefon: +86-571-8778-3511
Fax: +86-571-8778-3898
eMail: bie@hzcnc.com