Planta Med 2006; 72(15): 1359-1365
DOI: 10.1055/s-2006-951709
Original Paper
Pharmacology
© Georg Thieme Verlag KG Stuttgart · New York

A Study of the Neuroprotective Effect of the Phenolic Glucoside Gastrodin during Cerebral Ischemia in vivo and in vitro

Xianghui Zeng1 , Shaomin Zhang1 , Le Zhang1 , Keping Zhang1 , Xiaoxiang Zheng1
  • 1Department of Biomedical Engineering, Key Laboratory for Biomedical Engineering of Ministry of Education of China, Zhejiang University, Hangzhou, P. R. China
Further Information

Publication History

Received: March 7, 2006

Accepted: August 25, 2006

Publication Date:
06 November 2006 (online)

Abstract

The phenolic glucoside gastrodin (Gas) is a main component extracted from the rhizome of Gastrodia elata, a Chinese herbal medicine, which has long been used for treating dizziness, epilepsy, stroke and dementia. In this study, we investigated the neuroprotective effects of Gas on cerebral ischemic injury in rats caused by transient middle cerebral arterial occlusion (MCAO), oxygen/glucose deprivation (OGD) and glutamate-induced injury in cultured rat hippocampal neurons. Additionally, the effects of Gas on the extracellular glutamate level and changes in intracellular Ca2+ and the generation of nitric oxide (NO) were examined in cultured hippocampal neurons subjected to OGD in vitro. The results showed that the high dose of Gas (100 mg/kg) markedly decreased the infarct volume and edema volume, and improved the neurological functions after MCAO. Gas treatment (15 μg/mL, 30 μg/mL) also significantly inhibited OGD- and glutamate-induced neuronal cell death and reduced the extracellular glutamate level following OGD. Moreover, Gas treatment significantly inhibited the OGD-induced Ca2+ and NO increases. In conclusion, the present study indicates that Gas has a neuroprotective action.

References

  • 1 Zhou J, Yang Y B, Yang C R. Studies on the constituents of Gastrodia elata .  Acta Chim Sin. 1979;  37 183-9
  • 2 Wang M L, Lu X H, Wang F X. Observations of curative effect of Tianxuanqing injection on atheroscleotic vertebrobasilar ischemia.  Zhong Cao Yao. 2001;  32 823-5
  • 3 Wang Z R, Luo H L, Xiao J, Guo H L, Xue Z N. Arterial compliance and hemodynamics parameters response to gastrodin.  Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 1994;  11 197-201
  • 4 Ren S L, Yu L S. Effects of gastrodin on vascular resistance and tolerance to cerebral ischemia in mice.  Zhong Cao Yao. 1992;  23 359-62
  • 5 Xue L H, Tang Y P, Sun C L, Hong Q T. Gastrodin inhibits ischemia-induced membrane damage in cultured rat neurons.  J Beijing Univ Trad Chin Med. 1998;  21 18-21 [in Chinese]
  • 6 Hu J J, Hong Q T, Tang Y P, Sun C L. Protective effects of gastrodin against lesions in cultured astrocytes caused by simulated cerebral ischemia and reperfusion and its influence on the activity of nitric oxide synthase.  J Beijing Univ Trad Chin Med. 2001;  24 11-5 [in Chinese]
  • 7 Choi D W. Glutamate neurotoxicity and diseases of the nervous system.  Neuron. 1988;  1 623-34
  • 8 Choi D W. Glutamate neurotoxicity in cortical cell culture is calcium dependent.  Neurosci Lett. 1985;  58 293-7
  • 9 Jiang M H, Kaku T, Hada J, Hayashi Y. Different effects of eNOS and nNOS inhibition on transient forebrain ischemia.  Brain Res. 2002;  946 139-47
  • 10 Iadecola C. Bright and dark sides of nitric oxide in ischemic brain injury.  Trends Neurosci. 1997;  20 132-9
  • 11 Zea-Longa E, Weinstein P R, Carlson S, Cummins R. Reversible middle cerebral artery occlusion without craniectomy in rats.  Stroke. 1989;  20 84-91
  • 12 Hatfield R H, Gill R, Brazell C. The dose-response relationship and therapeutic window for dizocilpine (MK-801) in a rat focal ischemia model.  Eur J Pharmacol. 1992;  216 1-7
  • 13 Belayev L, Khoutorova L, Zhao W, Vigdorchik A, Belayev A, Busto R. et al . Neuroprotective effect of darbepoetin alfa, a novel recombinant erythropoietic protein, in focal cerebral ischemia in rats.  Stroke. 2005;  36 1065-70
  • 14 Isaev N K, Stelmashook E V, Dirnagl U, Andreeva N A, Manuhova L, Vorobjev V S. et al . Neuroprotective effects of the antifungal drug clotrimazole.  Neuroscience. 2002;  113 47-3
  • 15 Kelly S, Zhao H, Hua Sun G, Cheng D, Qiao Y, Luo J. et al . Glycogen synthase kinase 3beta inhibitor Chir025 reduces neuronal death resulting from oxygen-glucose deprivation, glutamate excitotoxicity, and cerebral ischemia.  Exp Neurol. 2004;  188 378-86
  • 16 Rupalla K, Cao W, Krieglstein J. Flupirtine protects neurons against excitotoxic or ischemic damage and inhibits the increase in cytosolic Ca2+ concentration.  Eur J Pharmacol. 1995;  294 469-73
  • 17 Hamasaki K, Kogure K, Ohwada K. A biological method for the quantitative measurement of tetrodotoxin (TTX): tissue culture bioassay in combination with a water-soluble tetrazolium salt.  Toxicon. 1996;  34 490-5
  • 18 Zhang M, Ning G M, Shou C H, Lu Y J, Hong D H, Zheng X X. Inhibitory effect of jujuboside A on glutamate-mediated excitatory signal pathway in hippocampus.  Planta Med. 2003;  69 692-5
  • 19 Al-Mehdi A B, Song C, Tozawa K, Fisher A B. Ca2+ and phosphatidylinositol 3-kinase- dependent nitric oxide generation in lung endothelial cells in situ with ischemia.  J Biol Chem. 2000;  275 39 807-10
  • 20 Zhang Z, Bourque C W. Calcium permeability and flux through osmosensory transduction channels of isolated rat supraoptic nucleus neurons.  Eur J Neurosci. 2006;  23 1491-500
  • 21 Choi D W, Rothman S M. The role of glutamate neurotoxicity in hypoxic-ischemic neuronal death.  Annu Rev Neurosci. 1990;  13 171-82
  • 22 Lees K R. Neuroprotection.  Br Med Bull. 2000;  56 401-12
  • 23 Mc Conkey D J, Orrenius S. The role of calcium in the regulation of apoptosis.  Biochem Biophys Res Commun. 1997;  239 357-66
  • 24 Elibol B, Soylemezoglu F, Unal I, Fujii M, Hirt L, Huang P L. et al . Nitric oxide is involved in ischemia-induced apoptosis in brain: a study in neuronal nitric oxide synthase null mice.  Neuroscience. 2001;  105 79-86
  • 25 Li W, Jin K, Nagayama T, He X, Chang J, Minami M. et al . Increased expression of apoptosis-linked gene 2 (ALG2) in the rat brain after temporary focal cerebral ischemia.  Neuroscience. 2000;  96 161-8
  • 26 Huang Z, Huang P L, Panahian N, Dalkara T, Fishman M C, Moskowitz M A. Effects of cerebral ischemia in mice deficient in neuronal nitric oxide synthase.  Science. 1994;  265 1883-5
  • 27 Kohno K, Ohta S, Furuta S, Kohno K, Kumon Y, Sakaki S. Intraventricular administration of nitric oxide synthase inhibitors prevents delayed neuronal death in gerbil hippocampal CA1 neurons.  Neurosci Lett. 1995;  199 65-8
  • 28 Choi J H, Yu B P. Brain synaptosomal aging: Free radicals and membrane fluidity.  Free Radic Biol Med. 1995;  18 133-9

Prof. Xiaoxiang Zheng

Department of Biomedical Engineering

Key Laboratory for Biomedical Engineering of Ministry of Education of China

Zhejiang University

Yuquan Campus

Hangzhou 310027

People’s Republic of China

Phone: +86-571-8795-1091

Fax: +86-571-8795-1676

Email: zxx@mail.hz.zj.cn

>