:: Volume 23, Issue 2 (Scientific Journal of Kurdistan University of Medical Sciences 2018) ::
SJKU 2018, 23(2): 114-124 Back to browse issues page
Investigation of the effect of Ginkgo biloba leaf extract on spatial memory impairment and hippocampal neuronal loss caused by diabetes induced by streptozotocin in rats
Abbas Alimoradian Dr1, Saeed Ghasemi2, Mohammad Zahiri2, Amir Hossein Saeedi2, Hossein Miladi3, Mehdi Sadegh Dr 4
1- Department of Pharmacology, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran.
2- Faculty of Paramedicine, Arak University of Medical Sciences, Arak, Iran.
3- Department of Pathology, Imam Khomeini Hospital, Arak, Iran.
4- Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran , m.sadegh@arakmu.ac.ir
Abstract:   (1922 Views)
Background and Aim: Learning and memory defect occurs following chronic diabetes with uncontrolled blood glucose. Ginkgo leaf extract improves brain blood flow. Also it contains antioxidant components and has shown beneficial effects in neurological diseases. In this study we investigated the effects of Ginkgo leaf extract on spatial memory impairment and hippocampal neuronal loss caused by diabetes.
Material and Methods: This experimental study included 28 adult male Sparague-Dawley rats. The rats were made diabetic by injection of streptozotocin (STZ: 60 mg/kg). Ginkgo leaf extract (40 mg/kg) was administrated orally every day for two weeks and its effects on memory impairment and hippocampal tissue damage were investigated. Spatial memory was assessed in Morris water maze for four days. Then, the brains of the animals were extracted and after tissue staining hippocampal tissue damage were evaluated by neuronal count.  
Results: Latency to find the platform in water maze were significantly increased in STZ group compared to that in the control group (p<0.05). While, administration of the Ginkgo extract in STZ injected animals significantly reduced the latency to find the platform (p<0.05). In addition, STZ reduced hippocampal neuronal count (p<0.001) and administration of the Ginkgo extract in STZ injected animals significantly improved hippocampal neuronal loss (p<0.01).
Conclusion: Ginkgo leaf extract significantly improved spatial memory impairment and hippocampal neuronal loss, induced by diabetes.
Keywords: Learning, Morris water maze, Neuronal count, Neuropathy.
Received: Dec 8, 2017     Accepted: Apr 9, 2018
Keywords: Learning, Morris water maze, Neuronal count, Neuropathy.
Full-Text [PDF 5172 kb]   (504 Downloads)    
Type of Study: Research | Subject: General
Received: 2018/05/31 | Accepted: 2018/05/31 | Published: 2018/05/31
1. 1. Van Dam PS, Cotter MA, Bravenboer B, Cameron NE. Pathogenesis of diabetic neuropathy: focus on neurovascular mechanisms. Eur J Pharmacol 2013; 719: 180-6. [DOI:10.1016/j.ejphar.2013.07.017]
2. Said G. Diabetic neuropathy--a review. Nat Rev Neurol 2007; 3: 331. [DOI:10.1038/ncpneuro0504]
3. Hoyer S. Memory function and brain glucose metabolism. Pharmacopsychiatry 2003; 36: 62-7. [DOI:10.1055/s-2003-40452]
4. Gispen WH, Biessels GJ. Cognition and synaptic plasticity in diabetes mellitus. Trends Neurosci 2000; 23: 542-9. [DOI:10.1016/S0166-2236(00)01656-8]
5. Whitmer RA, Gunderson EP, Barrett-Connor E, Quesenberry CP, Jr Yaffe K. Obesity in middle age and future risk of dementia: a 27 year longitudinal population based study. BMJ 2005; 330: 1360. [DOI:10.1136/bmj.38446.466238.E0]
6. Wang XF, Lin X, Li DY, Zhou R, Greenbaum J, Chen YC, et al. Linking Alzheimer's disease and type 2 diabetes: Novel shared susceptibility genes detected by cFDR approach. J Neurol Sci 2017; 380: 262-72. [DOI:10.1016/j.jns.2017.07.044]
7. Kamal MA, Priyamvada S, Anbazhagan AN, Jabir NR, Tabrez S, Greig NH. Linking Alzheimer's disease and type 2 diabetes mellitus via aberrant insulin signaling and inflammation. CNS Neurol Disord Drug Targets 2014; 13: 338-46. [DOI:10.2174/18715273113126660137]
8. Mushtaq G, Khan JA, Kamal MA. Biological mechanisms linking Alzheimer's disease and type-2 diabetes mellitus. CNS Neurol Disord Drug Targets 2014; 13: 1192-201. [DOI:10.2174/1871527313666140917114537]
9. Li ZG, Zhang W, Grunberger G, Sima AA. Hippocampal neuronal apoptosis in type 1 diabetes. Brain Res 2002; 946: 221-31. [DOI:10.1016/S0006-8993(02)02887-1]
10. Schmeichel AM, Schmelzer JD, Low PA. Oxidative injury and apoptosis of dorsal root ganglion neurons in chronic experimental diabetic neuropathy. Diabetes 2003; 165: 52-71. [DOI:10.2337/diabetes.52.1.165]
11. Vincent AM, Brownlee M, Russell JW. Oxidative stress and programmed cell death in diabetic neuropathy. Ann N Y Acad Sci 2002; 959: 368-83. [DOI:10.1111/j.1749-6632.2002.tb02108.x]
12. Said G, Lacroix C, Lozeron P, Ropert A, Planté V, Adams D. Inflammatory vasculopathy in multifocal diabetic neuropathy. Brain 2003; 126: 376-85. [DOI:10.1093/brain/awg029]
13. Magarinos AM, McEwen BS. Experimental diabetes in rats causes hippocampal dendritic and synaptic reorganization and increased glucocorticoid reactivity to stress. Proc Natl Acad Sci USA 2000; 97: 11056-61. [DOI:10.1073/pnas.97.20.11056]
14. Wu Y, Li S, Cui W, Zu X, Du J, Wang F. Ginkgo biloba extract improves coronary blood flow in healthy elderly adults: role of endothelium-dependent vasodilation. Phytomedicine 2008; 15: 164-9. [DOI:10.1016/j.phymed.2007.12.002]
15. Tian J, Liu Y, Chen K. Ginkgo biloba Extract in Vascular Protection: Molecular Mechanisms and Clinical Applications. Curr Vasc Pharmacol 2017; 15: 532-48. [DOI:10.2174/1570161115666170713095545]
16. Zhao M, Wang XX, Wan WH. Effects of the ginkgo biloba extract on the superoxide dismutase activity and apoptosis of endothelial progenitor cells from diabetic peripheral blood. Genet Mol Res 2014; 13: 220-7. [DOI:10.4238/2014.January.14.1]
17. He YT, Xing SS, Gao L, Wang J, Xing QC, Zhang W. Ginkgo biloba attenuates oxidative DNA damage of human umbilical vein endothelial cells induced by intermittent high glucose. Pharmazie 2014; 69: 203-7.
18. Shah ZA, Sharma P, Vohora SB. Ginkgo biloba normalises stress-elevated alterations in brain catecholamines, serotonin and plasma corticosterone levels. Eur Neuropsychopharmacol 2003; 13: 321-5. [DOI:10.1016/S0924-977X(03)00005-1]
19. Loffler T, Lee SK, Noldner M, Chatterjee SS, Hoyer S, Schliebs R. Effect of Ginkgo biloba extract (EGb761) on glucose metabolism-related markers in streptozotocin-damaged rat brain. J Neural Transm (Vienna) 2001; 108: 1457-74. [DOI:10.1007/s007020100020]
20. Nooshinfar E, Rezaei Tavirani M, Safaei A, Tambrchi Y. The Effect of Ginkgo on Baclofen Induced Amnesia using Passive Avoidance Learning and Memory in Rats. J Fasa Univ Med Sci 2015; 5: 62-8. [In Persian]
21. Charemboon T, Jaisin K. Ginkgo biloba for prevention of dementia: a systematic review and meta-analysis. J Med Assoc Thai 2015; 98: 508-13.
22. Cheng D, Liang B, Li Y. Antihyperglycemic effect of Ginkgo biloba extract in streptozotocin-induced diabetes in rats. Biomed Res Int 2013; 2013: 162724. [DOI:10.1155/2013/162724]
23. Saini AS, Taliyan R, Sharma PL. Protective effect and mechanism of Ginkgo biloba extract-EGb 761 on STZ-induced diabetic cardiomyopathy in rats. Pharmacogn Mag 2014; 10: 172-8. [DOI:10.4103/0973-1296.131031]
24. Sadegh M, Fathollahi Y, Naghdi N, Semnanian S. Morphine deteriorates spatial memory in sodium salicylate treated rats. Eur J Pharmacol 2013; 704: 1-6. [DOI:10.1016/j.ejphar.2013.02.017]
25. Tae HJ, Kang IJ, Lee TK, Cho JH, Lee JC, Shin MC, et al. Neuronal injury and tumor necrosis factor-alpha immunoreactivity in the rat hippocampus in the early period of asphyxia-induced cardiac arrest under normothermia. Neural Regen Res 2017; 12: 2007-13. [DOI:10.4103/1673-5374.221157]
26. Tuzcu M, Baydas G. Effect of melatonin and vitamin E on diabetes-induced learning and memory impairment in rats. Eur J Pharmacol 2006; 537: 106-10. [DOI:10.1016/j.ejphar.2006.03.024]
27. Zuo W, Yan F, Zhang B, Li J, Mei D. Advances in the Studies of Ginkgo Biloba Leaves Extract on Aging-Related Diseases. Aging Dis 2017; 8: 812-26. [DOI:10.14336/AD.2017.0615]
28. Wang SJ, Chen HH. Ginkgolide B, a constituent of Ginkgo biloba, facilitates glutamate exocytosis from rat hippocampal nerve terminals. Eur J Pharmacol 2005; 514: 141-9. [DOI:10.1016/j.ejphar.2005.03.027]
29. Huang SH, Duke RK, Chebib M, Sasaki K, Wada K, Johnston GA. Bilobalide, a sesquiterpene trilactone from Ginkgo biloba, is an antagonist at recombinant alpha1beta2gamma2L GABA(A) receptors. Eur J Pharmacol 2003; 464: 1-8. [DOI:10.1016/S0014-2999(03)01344-X]
30. Kalkunte SS, Singh AP, Chaves FC, Gianfagna TJ, Pundir VS, Jaiswal AK, et al. Antidepressant and antistress activity of GC-MS characterized lipophilic extracts of Ginkgo biloba leaves. Phytother Res 2007; 21: 1061-5. [DOI:10.1002/ptr.2212]
31. Yoshitake T, Yoshitake S, Kehr J. The Ginkgo biloba extract EGb and its main constituent flavonoids and ginkgolides increase extracellular dopamine levels in the rat prefrontal cortex. Br J Pharmacol 2010; 159: 659-68. [DOI:10.1111/j.1476-5381.2009.00580.x]
32. Wu T, Qiao S, Shi C, Wang S, Ji G. Metabolomics window into diabetic complications. J Diabetes Investig 2018; 9: 244-55. [DOI:10.1111/jdi.12723]
33. Khalil H. Diabetes microvascular complications-A clinical update. Diabetes Metab Syndr 2017; 11: S133-S9. [DOI:10.1016/j.dsx.2016.12.022]
34. Li Y, Zhang Y, Wen M, Zhang J, Zhao X, Zhao Y, et al. Ginkgo biloba extract prevents acute myocardial infarction and suppresses the inflammation and apoptosisregulating p38 mitogenactivated protein kinases, nuclear factor kappa B and B cell lymphoma 2 signaling pathways. Mol Med Rep 2017; 16: 3657-63. [DOI:10.3892/mmr.2017.6999]
35. Wang C, Wang B. Ginkgo Biloba Extract Attenuates Oxidative Stress and Apoptosis in Mouse Cochlear Neural Stem Cells. Phytother Res 2016; 30: 774-80. [DOI:10.1002/ptr.5572]
36. Rhee KJ, Lee CG, Kim SW, Gim DH, Kim HC, Jung BD. Extract of Ginkgo Biloba Ameliorates Streptozotocin-Induced Type 1 Diabetes Mellitus and High-Fat Diet-Induced Type 2 Diabetes Mellitus in Mice. Int J Med Sci 2015; 12: 987-94. [DOI:10.7150/ijms.13339]

XML   Persian Abstract   Print

Volume 23, Issue 2 (Scientific Journal of Kurdistan University of Medical Sciences 2018) Back to browse issues page