Journal of Korean Neurosurgical Society

The Korean Neurosurgical Society (대한신경외과학회)
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The Combined Effects of Ginkgo Biloba Extracts and Aspirin on Viability of SK-N-MC, Neuroblastoma Cell Line in Hypoxia and Reperfusion Condition

  • Moon, Sung-Hwan (Department of Neurosurgery, Seoul Medical Center) ;
  • Lee, Yong-Jik (Division of Clinical Research, Medical Institute, Seoul Medical Center) ;
  • Park, Soo-Yong (Department of Neurosurgery, Seoul Medical Center) ;
  • Song, Kwan-Young (Department of Neurosurgery, Seoul Medical Center) ;
  • Kong, Min-Ho (Department of Neurosurgery, Seoul Medical Center) ;
  • Kim, Jung-Hee (Department of Neurosurgery, Seoul Medical Center)
  • Received : 2010.11.26
  • Accepted : 2011.01.07
  • Published : 2011.01.28
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Abstract

Objective: The purpose of this study is to investigate the combined effects of ginkgo biloba extract, ginkgolide A and B and aspirin on SK-N-MC, human neuroblastoma cell viability and mRNA expression of growth associated protein43 (GAP43), Microtubule-associated protein 2 (MAP2), B-cell lymphoma2 (Bcl2) and protein53 (p53) gene in hypoxia and reperfusion condition. Methods: SK-N-MC cells were cultured with Dulbecco's Modified Eagle's Medium (DMEM) media in $37^{\circ}C$, 5% $CO_2$ incubator. The cells were cultured for 8 hours in non-glucose media and hypoxic condition and for 12 hours in normal media and $O_2$ concentration. Cell survival rate was measured with Cell Counting Kit-8 (CCK-8) reagent assay. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to estimate mRNA levels of GAP43, MAP2, Bcl2, and p53 genes. Results: The ginkgolide A and B increased viable cell number decreased in hypoxic and reperfused condition. The co-treatment of ginkgolide B with aspirin also increased the number of viable cells, however, there was no additive effect. Although there was no increase of mRNA expression of GAP43, MAP2, and Bcl2 in SK-N-MC cells with individual treatment of ginkgolide A, B or aspirin in hypoxic and reperfused condition, the co-treatment of ginkgolide A or B with aspirin significantly increased GAP43 and Bcl2 mRNA levels. In MAP2, only the co-treatment of ginkgolide A and aspirin showed increasing effect. The mRNA expression of p53 had no change in all treating conditions. Conclusion: This study suggests that the combined treatments of Ginkgo biloba extracts and aspirin increase the regeneration of neuroblastoma cells injured by hypoxia and reperfusion.

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References

  1. Ahlemeyer B, Krieglstein J : Neuroprotective effects of Ginkgo biloba extract. Cell Mol Life Sci 60 : 1779-1792, 2003 https://doi.org/10.1007/s00018-003-3080-1
  2. Araya R, Uehara T, Nomura Y : Hypoxia induces apoptosis in human neuroblastoma SK-N-MC cells by caspase activation accompanying cytochrome c release from mitochondria. FEBS Lett 439 : 168-172, 1998 https://doi.org/10.1016/S0014-5793(98)01363-5
  3. Chandrasekaran K, Mehrabian Z, Spinnewyn B, Chinopoulos C, Drieu K, Fiskum G : Neuroprotective effects of bilobalide, a component of Ginkgo biloba extract (EGb 761) in global brain ischemia and in excitotoxicity-induced neuronal death. Pharmacopsychiatry 36 Suppl 1 : S89-S94, 2003
  4. Chang LC, Huang N, Chou YJ, Kao FY, Hsieh PC, Huang YT : Patterns of combined prescriptions of aspirin-Ginkgo biloba in Taiwan : a population-based study. J Clin Pharm Ther 33 : 243-249, 2008 https://doi.org/10.1111/j.1365-2710.2008.00911.x
  5. Chen JX, Chen WZ, Huang HL, Chen LX, Xie ZZ, Zhu BY : Protective effects of Ginkgo biloba extract against lysophosphatidylcholine-induced vascular endothelial cell damage. Zhongguo Yao Li Xue Bao 19 : 359-363, 1998
  6. Cho CM, Ha SU, Bae HR, Huh JT : Endothelial cell products as a key player in hypoxia-induced nerve cell injury after stroke. J Korean Neurosurg Soc 40 : 103-109, 2006
  7. Cho JH, Sung JH, Cho EH, Won CK, Lee HJ, Kim MO, et al. : Gingko biloba Extract (EGb 761) prevents ischemic brain injury by activation of the Akt signaling pathway. Am J Chin Med 37 : 547-555, 2009 https://doi.org/10.1142/S0192415X09007041
  8. Chung C, Park SW, Kim YB, Hwang SN, Kim MK, Kwon JT, et al. : Apoptosis and the expression of p53, bcl-2 in very delayed focal cerebral infarction and penumbra. J Korean Neurosurg Soc 27 : 855-864, 1998
  9. Clark WM, Rinker LG, Lessov NS, Lowery SL, Cipolla MJ : Efficacy of antioxidant therapies in transient focal ischemia in mice. Stroke 32 : 1000-1004, 2001 https://doi.org/10.1161/01.STR.32.4.1000
  10. Gardner CD, Zehnder JL, Rigby AJ, Nicholus JR, Farquhar JW : Effect of Ginkgo biloba (EGb 761) and aspirin on platelet aggregation and platelet function analysis among older adults at risk of cardiovascular disease : a randomized clinical trial. Blood Coagul Fibrinolysis 18 : 787-793, 2007 https://doi.org/10.1097/MBC.0b013e3282f102b1
  11. Hamberg M, Samuelsson B : Prostaglandin endoperoxides. Novel transformations of arachidonic acid in human platelets. Proc Natl Acad Sci U S A 71 : 3400-3404, 1974 https://doi.org/10.1073/pnas.71.9.3400
  12. Janssens D, Remacle J, Drieu K, Michiels C : Protection of mitochondrial respiration activity by bilobalide. Biochem Pharmacol 58 : 109-119, 1999 https://doi.org/10.1016/S0006-2952(99)00061-1
  13. Ke XJ, Yu YF, Guo ZL, Xu K, Hai H, Zhang AH, et al. : The utilization status of aspirin for the secondary prevention of ischemic stroke. Chin Med J 122 (Engl) : 165-168, 2009
  14. Krieglstein J, Beck T, Seibert A : Influence of an extract of Ginkgo biloba on cerebral blood flow and metabolism. Life Sci 39 : 2327-2334, 1986 https://doi.org/10.1016/0024-3205(86)90663-6
  15. Lee CH : Annual report on the cause of death statistics 2006. Daejeon : Korea National Statistical Office, 2007, pp13
  16. Ma Y, Hei A, Jin Y : Beneficial effects of Ginkgo biloba injection on experimental focal cerebral ischemia in rats. J Cap Univ Med Sci 20 : 21-23, 1999
  17. Peng H, Li YF, Sun SG : Effects of Ginkgo biloba extract on acute cerebral ischemia in rats analyzed by magnetic resonance spectroscopy. Acta Pharmacol Sin 24 : 467-471, 2003
  18. Roth GJ, Majerus PW : The mechanism of the effect of aspirin on human platelets. I. Acetylation of a particulate fraction protein. J Clin Invest 56 : 624-632, 1975 https://doi.org/10.1172/JCI108132
  19. Saleem S, Zhuang H, Biswal S, Christen Y, Doré S : Ginkgo biloba extract neuroprotective action is dependent on heme oxygenase 1 in ischemic reperfusion brain injury. Stroke 39 : 3389-3396, 2008 https://doi.org/10.1161/STROKEAHA.108.523480
  20. Tadano T, Nakagawasai O, Tan-no K, Morikawa Y, Takahashi N, Kisara K : Effects of ginkgo biloba extract on impairment of learning induced by cerebral ischemia in mice. Am J Chin Med 26 : 127-132, 1998 https://doi.org/10.1142/S0192415X98000178
  21. Vartiainen N, Goldsteins G, Keksa-Goldsteine V, Chan PH, Koistinaho J : Aspirin inhibits p44/42 mitogen-activated protein kinase and is protective against hypoxia/reoxygenation neuronal damage. Stroke 34 : 752-757, 2003 https://doi.org/10.1161/01.STR.0000057813.31798.1F
  22. Wang H, Wang Y, Zhao X, Zhang Z, Miao Y : [Protective effects of folium Ginkgo extract on experimental cerebral ischemia of mice]. Zhongguo Zhong Yao Za Zhi 23 : 169-171, 1998
  23. Whitehead SN, Bayona NA, Cheng G, Allen GV, Hachinski VC, Cechetto DF : Effects of triflusal and aspirin in a rat model of cerebral ischemia. Stroke 38 : 381-387, 2007 https://doi.org/10.1161/01.STR.0000254464.05561.72
  24. Willis AL : An enzymatic mechanism for the antithrombotic and antihemostatic actions of aspirin. Science 183 : 325-327, 1974 https://doi.org/10.1126/science.183.4122.325
  25. Winn HR : Youmans Neurological Surgery, ed 5. vol. 2. Philadelphia : Saunders, 2004, pp1613
  26. Xu JP, Rui YC, Li TJ : Antagonistic effects of Ginkgo biloba extract on adhesion of monocytes and neutrophils to cultured cerebral microvascular endothelial cells. Zhongguo Yao Li Xue Bao 20 : 423-425, 1999
  27. Zhang Y, Gu D, Mao S, Chen W : [Protective effects of Ginkgo biloba extract on focal cerebral ischemia and thrombogenesis of carotid artery in rats]. Yao Xue Xue Bao 33 : 901-905, 1998
  28. Zhang YY, Li PF, Li D : Effect of Ginkgo biloba leaf extract on electroencephalography of rat with cerebral ischemia and reperfusion. Acta Pharmacol Sin 24 : 157-162, 2003
  29. Zhao HW, Li XY : Ginkgolide A, B, and huperzine A inhibit nitric oxide-induced neurotoxicity. Int Immunopharmacol 2 : 1551-1556, 2002 https://doi.org/10.1016/S1567-5769(02)00093-0
  30. Zhou L, Ming L, Jiang Q : [Protective effect of extract of folium ginkgo on repeated cerebral ischemia-reperfusion injury]. Zhongguo Zhong Xi Yi Jie He Za Zhi 20 : 356-358, 2000
  31. Zhuang H, Pin S, Christen Y, Doré S : Induction of heme oxygenase 1 by Ginkgo biloba in neuronal cultures and potential implications in ischemia. Cell Mol Biol (Noisy-le-grand) 48 : 647-653, 2002

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