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The effect of Ginkgo biloba extract on scopolamine-induced apoptosis in the hippocampus of rats

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Abstract

Apoptosis, known as programmed cell death, plays a crucial role in normal development and tissue homeostasis. Apoptosis is also involved in neurodegenerative diseases such as Alzheimer’s disease. Amnesia refers to the loss of memory and can also be a warning sign of neurodegenerative diseases. The antioxidant properties of Ginkgo biloba extract was known previously. Therefore, the aim of this study was to examine the effects of Ginkgo biloba extract on the rat’s hippocampal apoptotic neurons number after Scopolamine based amnesia. Thirty-six adult male Wistar rats were used. Rats were randomly divided into control, sham, protective and treatment groups. The rats in the sham group received only scopolamine hydrobromide (3 mg/kg) intraperitoneally. The rats in the protective and treatment groups received Ginkgo biloba extract (40, 80 mg/kg) for 7 days intraperitoneally before/after scopolamine injection. Then 48 h after the last injection, the brains of rats were withdrawn and fixed with paraformaldehyde, and then, after histological processing, the slices were stained with the TUNEL kit for apoptotic neurons. Data were compared by the ANOVA Post Hoc Tukey test; P < 0.05 was considered significant. Our results showed that Scopolamine (in the sham group) increased significantly the number of apoptotic neurons in all areas of the hippocampus compared with the control. Whereas, Ginkgo biloba extract reduce the neuronal apoptosis in the hippocampus before and/or after encounter with scopolamine. We concluded that pretreatment and treatment injection of Ginkgo biloba extract can have a protective effect for neurons and it can limit apoptosis in all area of the hippocampus.

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References

  • Ahlemeyer B, Krieglstein J (2003) Neuroprotective effects of Ginkgo biloba extract. Cell Mol Life Sci 60:1779–1792

    Article  PubMed  CAS  Google Scholar 

  • Ahlemeyer B, Möwes A, Krieglstein J (1999) Inhibition of serum deprivation-and staurosporine-induced neuronal apoptosis by Ginkgo biloba extract and some of its constituents. Eur J Pharmacol 367:423–430

    Article  PubMed  CAS  Google Scholar 

  • Azami NS, Jahanshahi M, Babapour V (2010) The role of CA1 α-adrenoceptor on scopolamine induced memory impairment in male rats. Physiol Pharmacol 14:66–77

    Google Scholar 

  • Barkats M, Venault P, Christen Y, Cohen-Salmon C (1994) Effect of long-term treatment with EGb 761 on age-dependent structural changes in the hippocampi of three inbred mouse strains. Life Sci 56:213–222

    Article  Google Scholar 

  • Bastianetto S, Ramassamy C, Dore S, Christen Y, Poirier J, Quirion R (2000a) The ginkgo biloba extract (EGb 761) protects hippocampal neurons against cell death induced by β-amyloid. Eur J Neurosci 12:1882–1890

    Article  PubMed  CAS  Google Scholar 

  • Bastianetto S, Zheng WH, Quirion R (2000b) The Ginkgo biloba extract (EGb 761) protects and rescues hippocampal cells against nitric oxide-induced toxicity. J Neurochem 74:2268–2277

    Article  PubMed  CAS  Google Scholar 

  • Caine ED, Weingartner H, Ludlow CL, Cudahy EA, Wehry S (1981) Qualitative analysis of scopolamine-induced amnesia. Psychopharmacology 74:74–80

    Article  PubMed  CAS  Google Scholar 

  • Chandrasekaran K, Mehrabian Z, Spinnewyn B, Chinopoulos C, Drieu K, Fiskum G (2003) Neuroprotective effects of bilobalide, a component of ginkgo biloba extract (EGb 761) in global brain ischemia and in excitotoxicity-induced neuronal death. Pharmacopsychiatry 36:89–94

    Google Scholar 

  • Chen C, Wei T, Gao Z et al (1999) Different effects of the constituents of EGb761 on apoptosis in rat cerebellar granule cells induced by hydroxyl radicals. IUBMB Life 47:397–405

    Article  CAS  Google Scholar 

  • Coursin D, Cihla H, Sempf J, Oberley T, Oberley L (1996) An immunohistochemical analysis of antioxidant and glutathione S-transferase enzyme levels in normal and neoplastic human lung

  • Das A, Shanker G, Nath C, Pal R, Singh S, Singh H (2002) A comparative study in rodents of standardized extracts of Bacopa monniera and Ginkgo biloba: anticholinesterase and cognitive enhancing activities. Pharmacol Biochem Behav 73:893–900

    Article  PubMed  CAS  Google Scholar 

  • Defeudis FV (1998) Ginkgo Biloba (Egb 761). From chemistry to the clinic.) Ullstein Medical

  • Defeudis F, Drieu K (2000) Ginkgo biloba extract (EGb 761) and CNS functions basic studies and clinical applications. Curr Drug Targets 1:25–58

    Article  PubMed  CAS  Google Scholar 

  • Domorakova I, Burda J, Mechírová E, Ferikova M (2006) Mapping of rat hippocampal neurons with NeuN after ischemia/reperfusion and Ginkgo biloba extract (EGb 761) pretreatment. Cell Mol Neurobiol 26:1191–1202

    Article  Google Scholar 

  • Emamian S, Naghdi N, Sepehri H, Jahanshahi M, Sadeghi Y, Choopani S (2010) Learning impairment caused by intra-CA1 microinjection of testosterone increases the number of astrocytes. Behav Brain Res 208:30–37

    Article  PubMed  CAS  Google Scholar 

  • Gertz HJ, Kiefer M (2004) Review about Ginkgo biloba special extract EGb 761 (Ginkgo). Curr Pharm Des 10:261–264

    Article  PubMed  CAS  Google Scholar 

  • Jahanshahi M, Sadeghi Y, Hosseini A (2006) Estimation of astrocyte number in different subfield of rat hippocampus. Pak J Biol Sci 9:1595–1597

    Article  Google Scholar 

  • Jahanshahi M, Sadeghi Y, Hosseini A, Naghdi N, Marjani A (2008) The effect of spatial learning on the number of astrocytes in the CA3 subfield of the rat hippocampus. Singapore Med J 49:388–391

    PubMed  CAS  Google Scholar 

  • Jahanshahi M, Golalipour M, Afshar M (2009) The effect of Urtica dioica extract on the number of astrocytes in the dentate gyrus of diabetic rats. Folia Morphologica 68:93–97

    PubMed  CAS  Google Scholar 

  • Jahanshahi M, Khoshnazar AK, Azami NS, Heidari M (2011) Radiation-induced lowered neurogenesis associated with shortened latency of inhibitory avoidance memory response. Folia Neuropathol 49:103–108

    PubMed  Google Scholar 

  • Johnson EMJR, Greenlund LJ, Akins PT, Hsu CY (1995) Neuronal apoptosis: current understanding of molecular mechanisms and potential role in ischemic brain injury. J Neurotrauma 12:843–852

    Article  PubMed  Google Scholar 

  • Kang X, Chen J, Xu Z, Li H, Wang B (2007) Protective effects of Ginkgo biloba extract on paraquat-induced apoptosis of PC12 cells. Toxicol In Vitro 21:1003–1009

    Article  PubMed  CAS  Google Scholar 

  • Kim MS, Lee JI, Lee WY, Kim SE (2004) Neuroprotective effect of Ginkgo biloba L. extract in a rat model of Parkinson’s disease. Phytotherapy Research 18:663–666

    Article  PubMed  CAS  Google Scholar 

  • Kokileva L (1994) Multi-step chromatin degradation in apoptosis. Int Arch Allergy Immunol 105:339–343

    Article  PubMed  CAS  Google Scholar 

  • Krieglstein J, Ausmeier F, El-Abhar H et al (1995) Neuroprotective effects of Ginkgo biloba constituents. Eur J Pharm Sci 3:39–48

    Article  CAS  Google Scholar 

  • Krištofiková Z, Klaschka J (1997) In vitro effect of Ginkgo Biloba extract (EGb 761) on the activity of presynaptic cholinergic nerve terminals in rat hippocampus. Dement Geriatr Cogn Disord 8:43–48

    Article  PubMed  Google Scholar 

  • Kuhn HG, Biebl M, Wilhelm D, Li M, Friedlander RM, Winkler J (2005) Increased generation of granule cells in adult Bcl-2-overexpressing mice: a role for cell death during continued hippocampal neurogenesis. Eur J Neurosci 22:1907–1915

    Article  PubMed  Google Scholar 

  • Lee MH, Kim H, Kim SS et al (2003) Treadmill exercise suppresses ischemia-induced increment in apoptosis and cell proliferation in hippocampal dentate gyrus of gerbils. Life Sci 73:2455–2465

    Article  PubMed  CAS  Google Scholar 

  • Liu J, Solway K, Messing RO, Sharp FR (1998) Increased neurogenesis in the dentate gyrus after transient global ischemia in gerbils. J Neurosci 18:7768–7778

    PubMed  CAS  Google Scholar 

  • Marcocci L, Maguire JJ, Droylefaix MT, Packer L (1994a) The nitric oxide-scavenging properties of Ginkgo biloba extract EGb 761. Biochem Biophys Res Commun 201:748–755

    Article  PubMed  CAS  Google Scholar 

  • Marcocci L, Packer L, Droy-Lefaix MT, Sekaki A, Gardes-Albert M (1994b) Antioxidant action of Ginkgo biloba extract EGb 761. Methods Enzymol 234:462–475

    Article  PubMed  CAS  Google Scholar 

  • Ni Y, Zhao B, Hou J, Xin W (1996) Preventive effect of Ginkgo biloba extract on apoptosis in rat cerebellar neuronal cells induced by hydroxyl radicals. Neurosci Lett 214:115–118

    Article  PubMed  CAS  Google Scholar 

  • Oberley T, Oberley L (1997) Antioxidant enzyme levels in cancer

  • Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates.) Academic Press, San Diego

  • Pulido MD, Parrish AR (2003) Metal-induced apoptosis: mechanisms. Mutat Res Fundam Mole Mech Mutagen 533:227–241

    Article  CAS  Google Scholar 

  • Rocher M-N, Carre D, Spinnewyn B et al (2011) Long-term treatment with standardized Ginkgo biloba Extract (EGb 761) attenuates cognitive deficits and hippocampal neuron loss in a gerbil model of vascular dementia. Fitoterapia 82:1075–1080

    Article  PubMed  Google Scholar 

  • Seif-El-Nasr M, Abd El-Fattah AA (1995) Lipid peroxide, phospholipids, glutathione levels and superoxide dismutase activity in rat brain after ischaemia: effect of Ginkgo biloba extract. Pharmacol Res 32:273–278

    Article  PubMed  CAS  Google Scholar 

  • Seifhosseini S, Jahanshahi M, Moghimi A, Aazami NS (2011) The effect of scopolamine on avoidance memory and hippocampal neurons in male Wistar rats. Basic Clin Neurosci 3:9–15

    Google Scholar 

  • Smith JV, Luo Y (2004) Studies on molecular mechanisms of Ginkgo biloba extract. Appl Microbiol Biotechnol 64:465–472

    Article  PubMed  CAS  Google Scholar 

  • Smith CD, Carney JM, Starke-Reed PE et al (1991) Excess brain protein oxidation and enzyme dysfunction in normal aging and in Alzheimer disease. Proc Natl Acad Sci 88:10540–10543

    Article  PubMed  CAS  Google Scholar 

  • Sun XQ, Xu ZP, Zhang S, Cao XS, Liu TS (2009) Simulated weightlessness aggravates hypergravity-induced impairment of learning and memory and neuronal apoptosis in rats. Behav Brain Res 199:197–202

    Article  PubMed  Google Scholar 

  • Thompson CB (1995) Apoptosis in the pathogenesis and treatment of disease. Science 267:1456–1462

    Article  PubMed  CAS  Google Scholar 

  • Wei T, Ni Y, Hou J, Chen C, Zhao B, Xin W (2000) Hydrogen peroxide-induced oxidative damage and apoptosis in cerebellar granule cells: protection by Ginkgo biloba extract. Pharmacol Res 41:427–433

    Article  PubMed  CAS  Google Scholar 

  • Williams B, Watanabe C, Schultz P, Rimbach G, Krucker T (2004) Age-related effects of Ginkgo biloba extract on synaptic plasticity and excitability. Neurobiol Aging 25:955–962

    Article  PubMed  Google Scholar 

  • Woodle ES, Kulkarni S (1998) Programmed cell death. Transplantation 66:681–691

    Article  PubMed  CAS  Google Scholar 

  • Xiao Q, Wang C, Li J et al (2010) Ginkgolide B protects hippocampal neurons from apoptosis induced by beta-amyloid 25–35 partly via up-regulation of brain-derived neurotrophic factor. Eur J Pharmacol 647:48–54

    Article  PubMed  CAS  Google Scholar 

  • Yu WH, Dong XQ, Hu YY, Huang M, Zhang ZY (2012) Ginkgolide B reduces neuronal cell apoptosis in the traumatic rat brain: possible involvement of Toll-like Receptor 4 and nuclear factor kappa B pathway. Phytotherapy Research in press

  • Zhang WR, Hayashi T, Kitagawa H et al (2000) Protective effect of ginkgo extract on rat brain with transient middle cerebral artery occlusion. Neurol Res 22:517–521

    PubMed  CAS  Google Scholar 

  • Zhivotovsky B, Wade D, Nicotera P, Orrenius S (1994) Role of nucleases in apoptosis. Int Arch Allergy Immunol 105:333–338

    Article  PubMed  CAS  Google Scholar 

  • Zhong C-B, Pan Y-P, Tong X-Y, Xu X-H, Wang X-L (2005) Delayed rectifier potassium currents and Kv2.1 mRNA increase in hippocampal neurons of scopolamine-induced memory-deficient rats. Neurosci Lett 373:99–104

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors would like to thank the Neuroscience Research Center for behavioral and histological experiments. We are also thankful for financial support of research affaisr of Golestan University of medical sciences. The authors would like to thank the NIAC Pharmaceutical Factory, Gorgan, Iran and Dr. Homan Bayat for donation of Gingko extract to the Neuroscience Research Center.

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Authors and Affiliations

  1. Department of Anatomy, Faculty of Medicine, Neuroscience Research Center, Golestan University of Medical Sciences, Km 4 Gorgan-Sari Road (Shastcola), Gorgan, Iran

    M. Jahanshahi

  2. Neuroscience Research Center, Golestan University of Medical Sciences, Gorgan, Iran

    E. G. Nickmahzar & F. Babakordi

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  1. M. Jahanshahi
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  2. E. G. Nickmahzar
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  3. F. Babakordi
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Correspondence to M. Jahanshahi.

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Jahanshahi, M., Nickmahzar, E.G. & Babakordi, F. The effect of Ginkgo biloba extract on scopolamine-induced apoptosis in the hippocampus of rats. Anat Sci Int 88, 217–222 (2013). https://doi.org/10.1007/s12565-013-0188-8

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  • DOI: https://doi.org/10.1007/s12565-013-0188-8

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