The Journal of Korean Medicine (대한한의학회지)

The Society of Korean Medicine (대한한의학회)
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Effect of Guibi-tang on Neuronal Apoptosis and Cognitive Impairment Induced by Beta Amyloid in Mice

  • Lee, Ju-Won (Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Cho, Dong-Guk (Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Cho, Woo-Sung (Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Ahn, Hyung-Gyu (Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Lee, Hyun-Joon (Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Shin, Jung-Won (Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Sohn, Nak-Won (Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University)
  • Received : 2014.10.09
  • Accepted : 2014.12.12
  • Published : 2014.12.30
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Abstract

Objectives: This study evaluated the effects of Guibi-tang (GBT) on neuronal apoptosis and cognitive impairment induced by beta amyloid ($A{\beta}$), (1-42) injection in the hippocampus of ICR mice. Methods: $A{\beta}$ (1-42) was injected unilaterally into the lateral ventricle using a Hamilton syringe and micropump ($2{\mu}g/3{\mu}{\ell}$, $0.6{\mu}{\ell}/min$). Water extract of GBT was administered orally once a day (500 mg/kg) for 3 weeks after the $A{\beta}$ (1-42) injection. Acquisition of learning and retention of memory were tested using the Morris water maze. Neuronal damage and $A{\beta}$ accumulation in the hippocampus was observed using cresyl violet and Congo red staining. The anti-apoptotic effect of GBT was evaluated using TUNEL labeling in the hippocampus. Results: GBT significantly shortened the escape latencies during acquisition training trials. GBT significantly increased the number of target headings to the platform site, the swimming time spent in the target quadrant, and significantly shortened the time for the 1st target heading during the retention test trial. GBT significantly attenuated the reduction in thickness and number of CA1 neurons, and $A{\beta}$ accumulation in the hippocampus produced by $A{\beta}$ (1-42) injection. GBT significantly reduced the number of TUNEL-labeled neurons in the hippocampus. Conclusion: These results suggest that GBT improved cognitive impairment by reducing neuronal apoptosis and $A{\beta}$ accumulation in the hippocampus. GBT may be a beneficial herbal formulation in treating cognitive impairment including Alzheimer's disease.

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References

  1. Blennow K, de Leon MJ, Zetterberg H. Alzheimer's disease. Lancet. 2006;368(9533):387-403. https://doi.org/10.1016/S0140-6736(06)69113-7
  2. Dickson DW. The pathogenesis of senile plaques. J Neuropathol Exp Neurol. 1997;56(4):321-39. https://doi.org/10.1097/00005072-199704000-00001
  3. Grundke-Iqbal I, Iqbal K, Quinlan M, Tung YC, Zaidi MS, Wisniewski HM. Microtubule-associated protein tau. A component of Alzheimer paired helical filaments. J Biol Chem. 1986;261(13):6084-9.
  4. Ball MJ. Neuronal loss, neurofibrillary tangles and granulovacuolar degeneration in the hippocampus with ageing and dementia. A quantitative study. Acta Neuropathol. 1977;37(2):111-8. https://doi.org/10.1007/BF00692056
  5. Kuhl DE, Koeppe RA, Minoshima S, Snyder SE, Ficaro EP, Foster NL, et al. In vivo mapping of cerebral acetylcholinesterase activity in aging and Alzheimer's disease. Neurology. 1999; 52(4):691-9. https://doi.org/10.1212/WNL.52.4.691
  6. Selkoe DJ. Amyloid beta-protein and the genetics of Alzheimer's disease. J Biol Chem. 1996;271(31):18295-8. https://doi.org/10.1074/jbc.271.31.18295
  7. Cacquevel M, Lebeurrier N, Cheenne S, Vivien D. Cytokines in neuroinflammation and Alzheimer's disease. Curr Drug Targets. 2004;5(6):529-34. https://doi.org/10.2174/1389450043345308
  8. Berezovska O, Lleo A, Herl LD, Frosch MP, Stern EA, Bacskai BJ, et al. Familial Alzheimer's disease presenilin 1 mutations cause alterations in the conformation of presenilin and interactions with amyloid precursor protein. J Neurosci. 2005;25(11):3009-17. https://doi.org/10.1523/JNEUROSCI.0364-05.2005
  9. Mhatre M, Floyd RA, Hensley K. Oxidative stress and neuroinflammation in Alzheimer's disease and amyotrophic lateral sclerosis: Common links and potential therapeutic targets. J Alzheimers Dis. 2004;6(2):147-57. https://doi.org/10.3233/JAD-2004-6206
  10. Roberson MR, Kolasa K, Parsons DS, Harrell LE. Cholinergic denervation and sympathetic ingrowth result in persistent changes in hippocampal muscarinic receptors. Neuroscience. 1997;80(2):413-8. https://doi.org/10.1016/S0306-4522(97)00153-X
  11. De Ferrari GV, Canales MA, Shin I, Weiner LM, Silman I, Inestrosa NC. A structural motif of acetylcholinesterase that promotes amyloid beta-peptide fibril formation. Biochemistry. 2001;40(35):10447-57. https://doi.org/10.1021/bi0101392
  12. Selkoe DJ, Schenk D. Alzheimer's disease: Molecular understanding predicts amyloid-based therapeutics. Annu Rev Pharmacol Toxicol. 2003;43:545-84. https://doi.org/10.1146/annurev.pharmtox.43.100901.140248
  13. Yates SL, Burgess LH, Kocsis-Angle J, Antal JM, Dority MD, Embury PB, et al. Amyloid beta and amylin fibrils induce increases in proinflammatory cytokine and chemokine production by THP-1 cells and murine microglia. J Neurochem. 2000;74(3):1017-25. https://doi.org/10.1046/j.1471-4159.2000.0741017.x
  14. Liang C, Yun NY, Jung SW, Kim DS, Lee YJ, Ma JY. Analysis of the components of guibitang and fermented guibi-tang and their ability to inhibit angiotensin-converting enzyme. Natural product sciences. 2011 2011/1.
  15. Korea Food & Drug Administration. The Korean herbal pharmacopeia. Seoul:Shinil books. 2013:505
  16. Kang IH, Lee I, Han SH, Moon BS. Effects of gwibitang on glutamate-induced apoptosis in C6 glial cells. The Journal of Korean Oriental Medicine. 2001;22(4):45-57.
  17. Jeon HJ, Park SW, Lee I, Mun BS. Effects of gwibitang on glutamate-induced death in rat neonatal astrocytes. The Journal of Korean Oriental Medicine. 2004;25(2):184-193.
  18. Lim JH. The Antioxidative and Neuroprotective Effect of Guibi-tang (Guipitang) and Guibi-tang gamibang (Guipitang jiaweijang) on PC12 cells. Journal of Oriental Neuropsychiatry. 2009;20(1):1-19.
  19. Oh MS, Huh Y, Bae H, Ahn DK, Park SK. The multi-herbal formula guibi-tang enhances memory and increases cell proliferation in the rat hippocampus. Neurosci Lett. 2005;379(3):205-8. https://doi.org/10.1016/j.neulet.2004.12.077
  20. Higashi K, Rakugi H, Yu H, Moriguchi A, Shintani T, Ogihara T. Effect of kihito extract granules on cognitive function in patients with Alzheimer's-type dementia. Geriatrics & Gerontology International. 2007;7(3):245-51. https://doi.org/10.1111/j.1447-0594.2007.00407.x
  21. Park CW, Lee JW, Chae H, Hong MC, Shin MK. Experimental study on the influence of the function of spleen on learning and memory. The Journal of Korean Oriental Medicine. 2000;20(4):39-49.
  22. Yan JJ, Cho JY, Kim HS, Kim KL, Jung JS, Huh SO, et al. Protection against beta-amyloid peptide toxicity in vivo with long-term administration of ferulic acid. Br J Pharmacol. 2001;133(1):89-96. https://doi.org/10.1038/sj.bjp.0704047
  23. KIM JW, KIM SJ. The Enhancing Effects of Gwibi-tang (guipi-tang) on Cognitive Function and Memory in Scopolamine-induced Dementia Rat Model. J Oriental Rehabilitation Medicine. 2012;22(3).
  24. Sisodia SS. Alzheimer's disease: Perspectives for the new millennium. J Clin Invest. 1999;104(9):1169-70. https://doi.org/10.1172/JCI8508
  25. Hook V, Schechter I, Demuth HU, Hook G. Alternative pathways for production of beta-amyloid peptides of Alzheimer's disease. Biol Chem. 2008;389(8):993-1006.
  26. Zussy C, Brureau A, Keller E, Marchal S, Blayo C, Delair B, et al. Alzheimer's disease related markers, cellular toxicity and behavioral deficits induced six weeks after oligomeric amyloid-beta peptide injection in rats. PLoS One. 2013;8(1):e53117. https://doi.org/10.1371/journal.pone.0053117
  27. Jameson LP, Smith NW, Dzyuba SV. Dye-binding assays for evaluation of the effects of small molecule inhibitors on amyloid (abeta) self-assembly. ACS Chem Neurosci. 2012;3(11):807-19. https://doi.org/10.1021/cn300076x
  28. Glenner GG, Eanes ED, Page DL. The relation of the properties of Congo red-stained amyloid fibrils to the -conformation. J Histochem Cytochem. 1972;20(10):821-6. https://doi.org/10.1177/20.10.821
  29. Zussy C, Brureau A, Delair B, Marchal S, Keller E, Ixart G, et al. Time-course and regional analyses of the physiopathological changes induced after cerebral injection of an amyloid beta fragment in rats. Am J Pathol. 2011;179(1):315-34. https://doi.org/10.1016/j.ajpath.2011.03.021
  30. Padurariu M, Ciobica A, Mavroudis I, Fotiou D, Baloyannis S. Hippocampal neuronal loss in the CA1 and CA3 areas of Alzheimer's disease patients. Psychiatr Danub. 2012;24(2):152-8.
  31. Shimohama S. Apoptosis in Alzheimer's disease--an update. Apoptosis. 2000;5(1):9-16. https://doi.org/10.1023/A:1009625323388
  32. Gavrieli Y, Sherman Y, Ben-Sasson SA. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol. 1992;119(3):493-501. https://doi.org/10.1083/jcb.119.3.493

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