DOI QR코드

DOI QR Code

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)
  • Published : 2007.09.30

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

References

  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 https://doi.org/10.1002/jnr.490290309
  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 https://doi.org/10.1016/S0006-8993(03)03224-4
  3. 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 https://doi.org/10.1016/S0024-3205(00)00858-4
  4. 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 https://doi.org/10.1161/01.STR.25.4.869
  5. 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 https://doi.org/10.1089/jop.1999.15.233
  6. 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 https://doi.org/10.2174/1389450003349380
  7. 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 https://doi.org/10.1002/ptr.1872
  8. 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 https://doi.org/10.1016/S0166-2236(99)01463-0
  9. 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 https://doi.org/10.1016/S0031-9422(01)00361-2
  10. Fisher, M. and Schaebitz, W. (2000). An overview of acutes stroke therapy: past, present, and future. Arch. Intern. Med. 160, 3196-3206 https://doi.org/10.1001/archinte.160.21.3196
  11. Han, Y. (2005). Ginkgo terpene component has an anti-inflammatory effect on Candida albicans-caused arthritic inflammation. Int. Immunopharmacol. 5, 1049-1056 https://doi.org/10.1016/j.intimp.2005.02.002
  12. 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 https://doi.org/10.1016/S0024-3205(02)01920-3
  13. 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
  14. 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 https://doi.org/10.1002/jnr.10251
  15. 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 https://doi.org/10.1016/S0006-2952(01)00866-8
  16. 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
  17. 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 https://doi.org/10.1161/01.STR.25.7.1469
  18. 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 https://doi.org/10.1161/01.STR.20.8.1037
  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 https://doi.org/10.1248/bpb.30.38
  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 https://doi.org/10.1023/A:1016244500596
  21. 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 https://doi.org/10.1248/bpb.29.985
  22. Tanahashi, N. and Fukuuchi, Y. (2002). Treatment of acute ischemic stroke: recent progress. Intern. Med. 41, 337-344 https://doi.org/10.2169/internalmedicine.41.337
  23. van Beek, T. A. (2002). Chemical analysis of Ginkgo biloba leaves and extracts. J. Chromatogr. A. 967, 21-55 https://doi.org/10.1016/S0021-9673(02)00172-3
  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 https://doi.org/10.1007/s002109900131
  25. 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 https://doi.org/10.1038/sj.jcbfm.9600324
  26. 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 https://doi.org/10.1111/j.1527-3458.2006.00009.x
  27. 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
  28. 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 https://doi.org/10.1179/016164104225014058

Cited by

  1. Ginkgo bilobaon Focal Cerebral Ischemia: A Systematic Review and Meta-Analysis vol.42, pp.04, 2014, https://doi.org/10.1142/S0192415X14500499