Skip to main content

Advertisement

SpringerLink
Log in

The Analog of Ginkgo biloba Extract 761 is a Protective Factor of Cognitive Impairment Induced by Chronic Fluorosis

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Ginkgo biloba extract EGb761 is widely used to treat patients with learning and memory impairment in Alzheimer’s disease and Parkinson’s disease in China. However, it is not yet clear whether the analog of EGb761 (EGb) has a protective effect on the learning and memory damage induced by chronic fluorosis. In this study, 30 Wistar rats were randomly divided into three groups: a control group, a sodium fluoride (NaF) + EGb group, and a NaF group. The rats were administered 0.5 ml water containing NaF (100 mg/l) and EGb (120 mg/kg) per day via gavage. After 3 months, the rats’ capacity for learning and memory was tested using a Y-maze. Damage to hippocampal neurons was evaluated by histological examination of the CA3 area. Superoxide dismutase (SOD) activity and the levels of glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) were measured. Furthermore, the expression levels of Bcl-2 and Bax and the levels of cleaved Caspase3 in the hippocampus were evaluated by RT-PCR and Western blotting. The results showed that EGb could improve learning and memory abilities, enhance the activities of SOD and GSH-Px, attenuate the level of MDA, upregulate the ratio of Bcl-2/Bax, and downregulate the level of cleaved Caspase3.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Ando M, Tadano M, Asanuma S, Tamura K, Matsushima S et al (1998) Health effects of indoor fluoride pollution from coal burning in China. Environ Health Perspect 106:239–244

    Article  PubMed  CAS  Google Scholar 

  2. Buzalaf MA, de Almeida BS, Cardoso VE, Olympio KP, Furlani Tde A (2004) Total and acid-soluble fluoride content of infant cereals, beverages and biscuits from Brazil. Food Addit Contam 21:210–215

    Article  PubMed  CAS  Google Scholar 

  3. Tschoppe P, Meyer-Lueckel H (2012) Effects of regular and highly fluoridated toothpastes in combination with saliva substitutes on artificial enamel caries lesions differing in mineral content. Arch Oral Biol 57:931–939

    Article  PubMed  CAS  Google Scholar 

  4. Blaszczyk I, Birkner E, Gutowska I, Romuk E, Chlubek D (2012) Influence of methionine and vitamin E on fluoride concentration in bones and teeth of rats exposed to sodium fluoride in drinking water. Biol Trace Elem Res 146:335–339

    Article  PubMed  CAS  Google Scholar 

  5. Spittle B (1994) Psychopharmacology of fluoride: a review. Int Clin Psychopharmacol 9:79–82

    Article  PubMed  CAS  Google Scholar 

  6. Chouhan S, Lomash V, Flora SJ (2010) Fluoride-induced changes in haem biosynthesis pathway, neurological variables and tissue histopathology of rats. J Appl Toxicol 30:63–73

    Article  PubMed  CAS  Google Scholar 

  7. Saxena S, Sahay A, Goel P (2012) Effect of fluoride exposure on the intelligence of school children in Madhya Pradesh, India. J Neurosci Rural Pract 3:144–149

    Article  PubMed  Google Scholar 

  8. Kaur T, Bijarnia RK, Nehru B (2009) Effect of concurrent chronic exposure of fluoride and aluminum on rat brain. Drug Chem Toxicol 32:215–221

    Article  PubMed  CAS  Google Scholar 

  9. Chen HGD, Fan HB (2011) The change of cognition induced by chronic fluoride in rats. Acta Acad Med Xuzhou 5:319–322

    Google Scholar 

  10. Guney M, Oral B, Take G, Giray SG, Mungan T (2007) Effect of fluoride intoxication on endometrial apoptosis and lipid peroxidation in rats: role of vitamins E and C. Toxicology 231:215–223

    Article  PubMed  CAS  Google Scholar 

  11. Liu YJ, Gao Q, Wu CX, Guan ZZ (2010) Alterations of nAChRs and ERK1/2 in the brains of rats with chronic fluorosis and their connections with the decreased capacity of learning and memory. Toxicol Lett 192:324–329

    Article  PubMed  CAS  Google Scholar 

  12. Pereira M, Dombrowski PA, Losso EM, Chioca LR, Da Cunha C et al (2011) Memory impairment induced by sodium fluoride is associated with changes in brain monoamine levels. Neurotox Res 19:55–62

    Article  PubMed  CAS  Google Scholar 

  13. Liu ME, Huang CC, Hwang JP, Yang AC, Tu PC et al (2011) Effect of Bcl-2 rs956572 SNP on regional gray matter volumes and cognitive function in elderly males without dementia. Age (Dordr) 35:343–352

    Article  CAS  Google Scholar 

  14. Engel T, Henshall DC (2009) Apoptosis, Bcl-2 family proteins and caspases: the ABCs of seizure-damage and epileptogenesis? Int J Physiol Pathophysiol Pharmacol 1:97–115

    PubMed  CAS  Google Scholar 

  15. He J, Yang Y, Yu Y, Li X, Li XM (2006) The effects of chronic administration of quetiapine on the methamphetamine-induced recognition memory impairment and dopaminergic terminal deficit in rats. Behav Brain Res 172:39–45

    Article  PubMed  CAS  Google Scholar 

  16. Abreu RV, Silva-Oliveira EM, Moraes MF, Pereira GS, Moraes-Santos T (2011) Chronic coffee and caffeine ingestion effects on the cognitive function and antioxidant system of rat brains. Pharmacol Biochem Behav 99:659–664

    Article  PubMed  CAS  Google Scholar 

  17. Kasper S, Schubert H (2009) Ginkgo biloba extract EGb 761 in the treatment of dementia: evidence of efficacy and tolerability. Fortschr Neurol Psychiatr 77:494–506

    Article  PubMed  CAS  Google Scholar 

  18. Janssen IM, Sturtz S, Skipka G, Zentner A, Velasco Garrido M et al (2010) Ginkgo biloba in Alzheimer's disease: a systematic review. Wien Med Wochenschr 160:539–546

    Article  PubMed  Google Scholar 

  19. Fehske CJ, Leuner K, Muller WE (2009) Ginkgo biloba extract (EGb761) influences monoaminergic neurotransmission via inhibition of NE uptake, but not MAO activity after chronic treatment. Pharmacol Res 60:68–73

    Article  PubMed  CAS  Google Scholar 

  20. Luo Y, Smith JV, Paramasivam V, Burdick A, Curry KJ et al (2002) Inhibition of amyloid-beta aggregation and caspase-3 activation by the Ginkgo biloba extract EGb761. Proc Natl Acad Sci U S A 99:12197–12202

    Article  PubMed  CAS  Google Scholar 

  21. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  PubMed  CAS  Google Scholar 

  22. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    PubMed  CAS  Google Scholar 

  23. Yan XB, Ouyang W, Li G, Duan KM (2012) Involvement of neuronal nitric oxide synthase in cognitive impairment in isoflurane-treated rats. Neurosci Lett 506:240–244

    Article  PubMed  CAS  Google Scholar 

  24. Xia Z, Zhang R, Wu P, Xia Z, Hu Y (2012) Memory defect induced by beta-amyloid plus glutamate receptor agonist is alleviated by catalpol and donepezil through different mechanisms. Brain Res 1441:27–37

    Article  PubMed  CAS  Google Scholar 

  25. Abdel-Wahab BA, Salama RH (2011) Venlafaxine protects against stress-induced oxidative DNA damage in hippocampus during antidepressant testing in mice. Pharmacol Biochem Behav 100:59–65

    Article  PubMed  CAS  Google Scholar 

  26. Cheng Z, Li N, Cheng J, Hu R, Gao G et al (2012) Signal pathway of hippocampal apoptosis and cognitive impairment of mice caused by cerium chloride. Environ Toxicol 27:707–718

    Article  PubMed  CAS  Google Scholar 

  27. Basha PM, Sujitha NS (2012) Combined influence of intermittent exercise and temperature stress on the modulation of fluoride toxicity. Biol Trace Elem Res 148:69–75

    Article  PubMed  CAS  Google Scholar 

  28. Head E (2009) Oxidative damage and cognitive dysfunction: antioxidant treatments to promote healthy brain aging. Neurochem Res 34:670–678

    Article  PubMed  CAS  Google Scholar 

  29. Sano M, Ernesto C, Thomas RG, Klauber MR, Schafer K et al (1997) A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study. N Engl J Med 336:1216–1222

    Article  PubMed  CAS  Google Scholar 

  30. Sultana R, Banks WA, Butterfield DA (2010) Decreased levels of PSD95 and two associated proteins and increased levels of BCl2 and caspase 3 in hippocampus from subjects with amnestic mild cognitive impairment: insights into their potential roles for loss of synapses and memory, accumulation of Abeta, and neurodegeneration in a prodromal stage of Alzheimer's disease. J Neurosci Res 88:469–477

    PubMed  CAS  Google Scholar 

  31. Korsmeyer SJ (1999) BCL-2 gene family and the regulation of programmed cell death. Cancer Res 59:1693s–1700s

    PubMed  CAS  Google Scholar 

  32. Lee JH, Jung JY, Jeong YJ, Park JH, Yang KH et al (2008) Involvement of both mitochondrial- and death receptor-dependent apoptotic pathways regulated by Bcl-2 family in sodium fluoride-induced apoptosis of the human gingival fibroblasts. Toxicology 243:340–347

    Article  PubMed  CAS  Google Scholar 

  33. Kirkland RA, Saavedra GM, Cummings BS, Franklin JL (2010) Bax regulates production of superoxide in both apoptotic and nonapoptotic neurons: role of caspases. J Neurosci 30:16114–16127

    Article  PubMed  CAS  Google Scholar 

  34. Yang S, Wang Z, Farquharson C, Alkasir R, Zahra M et al (2011) Sodium fluoride induces apoptosis and alters bcl-2 family protein expression in MC3T3-E1 osteoblastic cells. Biochem Biophys Res Commun 410:910–915

    Article  PubMed  CAS  Google Scholar 

  35. Koh PO (2009) Gingko biloba extract (EGb 761) prevents increase of Bad-Bcl-XL interaction following cerebral ischemia. Am J Chin Med 37:867–876

    Article  PubMed  Google Scholar 

  36. Jiang X, Nie B, Fu S, Hu J, Yin L et al (2009) EGb761 protects hydrogen peroxide-induced death of spinal cord neurons through inhibition of intracellular ROS production and modulation of apoptotic regulating genes. J Mol Neurosci 38:103–113

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by grants CXZZ11-0747 from the Creative Project of University Students in Jiangsu Province, Jsb 11101 from the open project of the Key Laboratory of Brain Diseases Bioinformation in Jiangsu Province, China, and SBK201221577 from the Natural Science Foundation of Jiangsu Province, China.

Conflict of Interest

There is no conflict of interest to disclose.

Author information

Authors and Affiliations

  1. Department of Neurology, Xuzhou Medical College Affiliated Hospital, Huaihai Road No.99, Xuzhou, Jiangsu Province, 221000, China

    Caiyi Zhang, Chao Ren, Hao Chen, Runlu Geng, Hongbin Fan & Deqin Geng

  2. Department of Psychiatry, Xuzhou Dongfang Hospital, Xuzhou, Jiangsu Province, China

    Caiyi Zhang & Houfeng Zhao

  3. Tumorbiological Laboratory, Neurosurgical Clinic, Ludwig-Maximilians-Universität München, Munich, Germany

    Ketai Guo

  4. Key Laboratory of Brain Diseases Bioinformation, Xuzhou, Jiangsu Province, China

    Caiyi Zhang & Deqin Geng

Authors
  1. Caiyi Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chao Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hao Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Runlu Geng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hongbin Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Houfeng Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ketai Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Deqin Geng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Deqin Geng.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, C., Ren, C., Chen, H. et al. The Analog of Ginkgo biloba Extract 761 is a Protective Factor of Cognitive Impairment Induced by Chronic Fluorosis. Biol Trace Elem Res 153, 229–236 (2013). https://doi.org/10.1007/s12011-013-9645-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-013-9645-4

Keywords

Search

Navigation