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Protective effect of Shenqi-wan and its fractions on N-methyl-D-aspartate-induced excitotoxicity in rat hippocampus

  • Lee, Joung-Hun (Department of Anatomy-Pointology, College of Oriental Medicine, Kyungwon University) ;
  • Kim, Youn-Sub (Department of Anatomy-Pointology, College of Oriental Medicine, Kyungwon University) ;
  • Kim, Young-Sick (Department of Physiology, College of Medicine, Kyung Hee University) ;
  • Kim, Sung-Eun (Department of Physiology, College of Medicine, Kyung Hee University) ;
  • Sung, Yun-Hee (Department of Physiology, College of Medicine, Kyung Hee University) ;
  • Kim, Bo-Kyun (Department of Physiology, College of Medicine, Kyung Hee University) ;
  • Lee, Jin-Woo (Department of Physiology, College of Medicine, Kyung Hee University) ;
  • Ham, Dae-Hyun (Acupuncture and Meridian Science Research Center, Kyung Hee University) ;
  • Lee, Hye-Jung (Acupuncture and Meridian Science Research Center, Kyung Hee University) ;
  • Kim, Chang-Ju (Department of Physiology, College of Medicine, Kyung Hee University)
  • Published : 2008.02.29

Abstract

Shenqi-wan, Oriental herbal medicine formulation, has traditionally been used for the treatment of delayed mental and physical development in children, complications of diabetes, and glomerulonephritis. In the present study, we investigated the protective effect of the aqueous extract of Shenqi-wan and its fractions against N-methyl-D-aspartate (NMDA)-induced exitotoxicity in rat hippocampal CA1 neurons. Fractions were elucidated at 0 - 10 min, 11 - 20 min, and 21 - 30 min by using gravity column chromatography method. In the present results, treatment with NMDA on cultured hippocampal slices induced neuronal death in the hippocampal CA1 region. Pretreatment with the Shenqi-wan did not exerted protective effect, however its fractions suppressed NMDA-induced neuronal damage. The fraction elucidated at 11 - 20 min showed the most potent protective effect. These results revealed that effective substances of the Shenqi-wan against NMDA-induced excitotoxicity may exist mainly in the fraction elucidated at 11 - 20 min.

Keywords

References

  1. Andras IE, Deli MA, Veszelka S, Hayashi K, Hennig B, Toborek M. (2007) The NMDA and AMPA/KA receptors are involved in glutamate-induced alterations of occludin expression and phosphorylation in brain endothelial cells. J. Cereb. Blood Flow Metab. 27, 1431-1443 https://doi.org/10.1038/sj.jcbfm.9600445
  2. Chen Y, Wei L, Ma M, Wu G, Zhang G and Wei Z. (1997) Effect of jiawei shenqi dihuang tang on the content of urinary protein in patients with diabetic nephrothy. J. Tradit. Chin. Med. 17, 184-186
  3. Gee CE, Benquet P, Raineteau O, Rietschin L, Kirbach SW, Gerber U. (2006) NMDA receptors and the differential ischemic vulnerability of hippocampal neurons. Eur. J. Neurosci. 23, 2595-2603 https://doi.org/10.1111/j.1460-9568.2006.04786.x
  4. Gunasekar PG, Kanthasamy AG, Borowitz JL, Isom GE. (1995) NMDA receptor activation produces concurrent generation of nitric oxide and reactive oxygen species, implication for cell death. J. Neurochem. 65, 2016-2021
  5. Kim E, Raval AP, Defazio RA, Perez-Pinzon MA. (2007) Ischemic preconditioning via epsilon protein kinase C activation requires cyclooxygenase-2 activation in vitro. Neuroscience 145, 931-941 https://doi.org/10.1016/j.neuroscience.2006.12.063
  6. Kwak S, Weiss JH. (2006) Calcium-permeable AMPA channels in neurodegenerative disease and ischemia. Curr. Opin. Neurobiol. 16, 281-287 https://doi.org/10.1016/j.conb.2006.05.004
  7. Lee J, Son D, Lee P, Kim DK, Shin MC, Jang MH, Kim CJ, Kim YS, Kim SY, Kim H. (2003) Protective effect of methanol extract of Uncaria rhynchophylla against excitotoxicity induced by N-methyl-Daspartate in rat hippocampus. J. Pharmacol. Sci. 92, 70-73 https://doi.org/10.1254/jphs.92.70
  8. McCarran WJ, Goldberg MP. (2007) White matter axon vulnerability to AMPA/kainate receptormediated ischemic injury is developmentally regulated. J. Neurosci. 27, 4220-4229 https://doi.org/10.1523/JNEUROSCI.5542-06.2007
  9. Shin HT, Chung SH, Lee JS, Kim SS, Shin HD, Jang MH, Shin MC, Bahn GH, Paik EK, Park JH, Kim CJ. (2003) Protective effect of Shenqi-wan against $H_2O_2$- induced apoptosis in hippocampal neuronal cells. Am. J. Chin. Med. 31, 675-686 https://doi.org/10.1142/S0192415X03001454
  10. Simon RP, Swan JH, Griffiths T, Meldrum BS. (1984) Blockade of N-methyl-D-aspartate receptors may protect against ischemic damage in the brain. Science 226, 850-852 https://doi.org/10.1126/science.6093256
  11. Tong CM, Shepherd D, Jahr CE. (1995) Synaptic desensitization of NMDA receptors by calcineurin. Science 267, 1510-1512 https://doi.org/10.1126/science.7878472
  12. Verkhratsky A, Kirchhoff F. (2007) NMDA Receptors in glia. Neuroscientist 13, 28-37 https://doi.org/10.1177/1073858406294270
  13. Wang J, Zhang DS. (1987) Effect of Shenqi-wan on immunological function in the nephrotic syndrome of chronic glomerulonephritis patients. Zhong Xi Yi Jie Za Zhi 7, 731-733
  14. Xu J, Zhang QG, Li C, Zhang GY. (2007) Subtoxic Nmethyl- D-aspartate delayed neuronal death in ischemic brain injury through TrkB receptor- and calmodulin-mediated PI-3K/Akt pathway activation. Hippocampus 17, 525-537 https://doi.org/10.1002/hipo.20289
  15. Yang S, Zhou W, Zhang Y, Yan C, Zhao Y. (2006) Effects of Liuwei Dihuang decoction on ion channels and synaptic transmission in cultured hippocampal neuron of rat. J. Ethnopharmacol. 106, 166-172 https://doi.org/10.1016/j.jep.2005.12.017