Browse > Article
http://dx.doi.org/10.4062/biomolther.2007.15.3.169

Neuroprotective Effects of Ginkgo biloba extract, GBB, in the Transient Ischemic Rat Model  

Oh, Jin-Kyung (Department of Oriental Pharmaceutical Science and Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy)
Jung, Ji-Wook (Department of Herbal Medicinal Resource, College of Health and Welfare, Daegu Haany University)
Oh, Hye-Rim (Department of Oriental Pharmaceutical Science and Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy)
Han, Yong-Nam (Department of Pharmaceutical Science, College of Pharmacy, Seoul National University)
Ryu, Jong-Hoon (Department of Oriental Pharmaceutical Science and Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Department of Department of Life and Nanopharmaceutical Science, Kyung Hee University)
Publication Information
Biomolecules & Therapeutics / v.15, no.3, 2007 , pp. 169-174 More about this Journal
Abstract
In the present study, we investigated the neuroprotective effects of standardized Ginkgo biloba extract (GBB) (total terpene trilactones, 13 ${\pm}$ 3%; biflavone, 4.5 ${\pm}$ 1.5%; flavonol glycoside, < 8%; proanthocyanidine, under detection limit) on ischemia-reperfusion-induced brain injury in the rats. Ischemia was induced by the intraluminal occlusion of the right middle cerebral artery for 2 h and reperfusion was continued for 22 h. GBB was orally administered, promptly prior to reperfusion and 2 h after. Total infarction volume in the ipsilateral hemispheres of ischemia-reperfusion rats were significantly reduced by treatment with GBB in a dose-dependent manner (P<0.05). The therapeutic time window of GBB was 3 h in this ischemia-reperfusion rat model. Furthermore, GBB also significantly inhibited increased neutrophil infiltration of ischemic brain tissue, as estimated by myeloperoxidase activity. These findings suggest that GBB plays a crucial protective role in ischemia-induced brain injury, in part, via inhibition of neutrophil infiltration, and suggest that this GBB could serve as a neuroprotective agent following transient focal ischemic brain injury.
Keywords
Gingko biloba; Ischemia-reperfusion; Neutrophil; Myeloperoxidase;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Barone, F. C., Hillegass, L. M., Price, W. J., White, R. F., Lee, E. V., Feuerstein, G. Z., Sarau, H. M., Clark, R. K. and Griswold, D. E. (1991). Polymorphonuclear leukocyte infiltration into cerebral focal ischemic tissue: myeloperoxidase activity assay and histologic verification. J. Neurosci. Res. 29, 336-345   DOI   ScienceOn
2 Beray-Berthat, V., Croci, N., Plotkine, M. and Margaill I. (2003). Polymorphonuclear neutrophils contribute to infarction and oxidative stress in the cortex but not in the striatum after ischemia-reperfusion in rats. Brain Res. 987, 32-38   DOI   ScienceOn
3 Fisher, M. and Schaebitz, W. (2000). An overview of acutes stroke therapy: past, present, and future. Arch. Intern. Med. 160, 3196-3206   DOI   ScienceOn
4 Calapai, G., Crupi, A., Firenzuoli, F., Marciano, M. C., Squadrito, F., Inferrera, G., Parisi, A., Rizzo, A., Crisafulli, C., Fiore, A. and Caputi, A. P. (2000). Neuroprotective effects of Ginkgo billoba extract in brain ischemia are mediated by inhibition of nitric oxide synthesis. Life Sci. 67, 2673-2683   DOI   ScienceOn
5 Chopp, M., Zhang, R. L., Chen, H., Li, Y., Jiang, N. and Rusche, J. R. (1994). Postischemic administration of an anti-Mac-1 antibody reduces ischemic cell damage after transient middle cerebral artery occlusion in rats. Stroke 25, 869-875   DOI   ScienceOn
6 Chung, H. S., Harris, A., Kristinsson, J. K., Ciulla, T. A., Kagemann, C. and Ritch, R. (1999). Ginkgo biloba extract increase ocular blood flow velocity. J. Ocular Pharmacol. Ther. 15, 233-240   DOI   ScienceOn
7 DeFeudis, F. V. and Drieu, K. (2000). Ginkgo biloba extract (Egb 761) and CNS functions: basic studies and clinical applications. Curr. Drug Targets 1, 25-58   DOI
8 De Lima, K. C., Schilichting, C. L., Junior, L. A., da Silva, F. M., Benetoli, A. and Milani, H. (2006). The Ginkgo biloba extract, EGb 761, fails to reduce brain infarct size in rats after transient, middle cerebral artery occlusion in conditions of unprevented, ischemia-induced fever. Phytother. Res. 20, 438-443   DOI   ScienceOn
9 De Keyser, J., Sulter, G. and Luiten P. G. (1999). Clinical trials with neuroprotective drugs in acute ischemic stroke: are we doing the right thing? Trends Neurosci. 22, 535-540   DOI   ScienceOn
10 Deters, A., Dauer, A., Schnetz, E., Fartasch, M. and Hensel, A. (2001). High molecular compounds (polysaccharides and proanthocyanidins) from Hamamelis virginiana bark: influence on human skin keratinocyte proliferation and differentiation and influence on irritated skin. Phytochemistry 58, 949-958   DOI   ScienceOn
11 Lee, E .J., Chen, H. Y., Wu, T. S., Chen, T. Y., Ayoub, I. A. and Maynard, K. I. (2002). Acute administration of Ginkgo biloba extract (EGb 761) affords neuroprotection against permanent and transient focal cerebral ischemia in Sprague-Dawley rats. J. Neurosci. Res. 68, 636-645   DOI   ScienceOn
12 Matsuo, T., Onodere, H., Shiga, Y., Nakamura, M., Ninomiya, M., Kihar, T. and Kogure, K. (1994). Correlation between myeloperoxidase-quantified neutrophil accumulation and ischemic brain injury in the rat. Stroke 25, 1469-1475   DOI   ScienceOn
13 Nagasawa, H. and Kogure, K. (1989). Correlation between cerebral blood flow and histologic changes in a new rat model of middle cerebral artery occlusion. Stroke 20, 1037-1043   DOI   ScienceOn
14 Lenoir, M., Pedruzzi, E., Rais, S., Drieu, K. and Perianin, A. (2002). Sensitization of human neutrophil defense activities through activation of platelet-activating factor receptors by ginkgolide B, a bioactive component of the Ginkgo biloba extract EGb 761. Biochem. Pharmacol. 63, 1241-1249   DOI   ScienceOn
15 Han, Y. (2005). Ginkgo terpene component has an anti-inflammatory effect on Candida albicans-caused arthritic inflammation. Int. Immunopharmacol. 5, 1049-1056   DOI   ScienceOn
16 Hwang, Y. S., Shin, C. Y., Huh, Y. and Ryu, J.H. (2002). Hwangryun-Hae-Dok-tang (Huanglian-Jie-Du-Tang) extract and its constituents reduce ischemia-reperfusion brain injury and neutrophil infiltration in rats. Life Sci. 71, 2105-2117   DOI   ScienceOn
17 Kudolo, G. E., Dorsey, S. and Blodgett, J. (2003). Effect of ingestion of Ginkgo biloba extract on platelet aggregation and urinary prostanoid excretion in healthy and type 2 diabetic subjects. Thromb Res. 108, 151-160
18 Li, Z., Lin, X. M., Gong P. L., Du, G. H. and Zeng, F. D. (2005) Effects of gingko biloba extract on glutamate-induced [$Ca^{2+}$]i changes in cultured cortical astrocytes after hypoxia/reoxyenation, $H_2O_2$ or L-glutamate injury. Yao Xue Xue Bao. 40, 213-219
19 Oh, J. K., Hyun, S. Y., Oh, H. R., Jung, J. W., Park, C., Lee, S. Y., Park, J. H., Kim, K. H., Kim, Y. K. and Ryu, J. H. (2007). Effects of Anemarrhena asphodeloides on focal ischemic brain injury induced by middle cerebral artery occlusion in rats. Biol. Pharm. Bull. 30, 38-43   DOI   ScienceOn
20 Pardridge, W. M., Kang, Y. S., BuciaK, J. L. and Yang, J. (1995). Human insulin receptor monoclonal antibody undergoes high affinity binding to human brain capillaries in vitro and rapid transcytosis through the blood-brain barrier in vivo in the primate. Pharm. Res. 12, 807-816   DOI
21 Weston, R. M., Jones, N. M., Jarrott, B. and Callaway, J. K. (2007). Inflammatory cell infiltration after endothelin-1-induced cerebral ischemia: histochemical and myeloperoxidase correlation with temporal changes in brain injury. J. Cereb. Blood Flow Metab. 27, 100-114   DOI   ScienceOn
22 Park, Y. M., Won, J. H., Yun, K. J., Ryu, J. H., Han, Y. N., Choi, S. K. and Lee, K. T. (2006). Preventive effect of Ginkgo biloba extract (GBB) on the lipopolysaccharide-induced expressions of inducible nitric oxide synthase and cyclooxygenase-2 via suppression of nuclear factor-kappa B in RAW 264.7 cells. Biol. Pharm. Bull. 29, 985-990   DOI   ScienceOn
23 Tanahashi, N. and Fukuuchi, Y. (2002). Treatment of acute ischemic stroke: recent progress. Intern. Med. 41, 337-344   DOI
24 Weichel, O., Hilgert, M., Chatterjee, S. S., Lehr, M. and Klein, J. (1999). Bilobalide, a constituent of Ginkgo biloba, inhibits NMDAinduced phospholipase A2 activation and phospholipids breakdown in rat hippocampus. Naunyn Schmiedebergs Arch. Pharmacol. 360, 609-615   DOI
25 Yoshida, H., Yanai, H., Namiki, Y., Fukatsu-Sasaki, K., Furutani, N. and Tada, N. (2006). Neuroprotective effects of edaravone: a novel free radical scavenger in cerebrovascular injury. CNS Drug Rev. 12, 9-20   DOI   ScienceOn
26 Zhang, J., Fu, S., Liu, S., Mao, T. and Xiu, R. (2000). The therapeutic effect of Ginkgo biloba extract in SHR rats and its possible mechanism based on cerebral microvascular flow and vasomotion. Clin Hemorheol Microcirc. 23, 133-138
27 Zhang, W., Sato, K., Hayashi, T., Omori, N., Nagano, I., Kato, S., Horiuchi, S. and Abe, K. (2004). Extension of ischemic therapeutic time window by a free radical scavenger, Edaravone, reperfused with tPA in rat brain. Neurol. Res. 26, 342-348   DOI   ScienceOn
28 van Beek, T. A. (2002). Chemical analysis of Ginkgo biloba leaves and extracts. J. Chromatogr. A. 967, 21-55   DOI   ScienceOn