Chukmesundan (CMSD), composed of the following 8 medicinal herbs including Panex ginseng C.A. MEYER, Atractylodes macrocephala KOID, Poria cocos WOLF, Pinellia ternata BREIT, Brassica alba BOISS, Aconitum carmichaeli DEBX, Cynanchum atratum BGE and Cuscuta chinensis LAM. CMSD is being used in Korea for the treatment of various symptoms accompanying hypertension and cerebrovascular disorders. This study was carried out to examine the effects of CMSD on cultured primary neuron cell, cell cytotoxicity and lipid peroxidation in Aβ-treated cells. Cell death was enhanced by addition of Aβ. Pretreatment of CMSD attenuated in cell killing induced by Aβ. The protective effect of the CMSD water extracts on Aβ-induced neuronal death was also observed by lactate dehydrogenase assay using cultured astrocyte cells. Aβ-induced cell death was protected by the water extract of CMSD in a dose-dependent manner, and 25–50 μg/ml was the most effective concentration. CMSD has been also shown to protect primary cultured neurons from N-methyl-d-aspartate receptor-mediated glutamate toxicity. It was in vivo evidenced that CMSD protects neurons against ischemia-induced cell death. Moreover, oral administration of CMSD into mice prevented ischemia-induced learning disability and rescued hippocampal CA1 neurons from lethal ischemic damage. The neuroprotective action of exogenous CMSD was also confirmed by counting synapses in the hippocampal CA1 region. The presence of CMSD in neuron cultures rescued the neurons from nitrogen oxide (NO)-induced death. From these, it was suggested that CMSD may exert its neuroprotective effect by reducing the NO-mediated formation of free radicals or antagonizing their toxicity.
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Abbreviations
- Aβ :
-
Amyloid-β
- CDNB:
-
1-chloro-2,4-dinitrobenzene
- CMSD:
-
Chuk-Me-Sun-Dan
- DMEM:
-
Dulbecco’s Modified Eagle’s Medium
- DMSO:
-
dimethyl sulfoxide
- EDTA:
-
ethylenediamine tetraacetic acid
- LDH:
-
lactate dehydrogenase
- Me-TC:
-
S-methyl-L-thiocitrulline
- MTT:
-
3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide
- NBT:
-
nitro blue tetrazolium
- NMDA:
-
N-methyl-d-aspartate
- NO:
-
nitrogen oxide
- NOS:
-
nitrogen oxide synthase
- PBS:
-
phosphate-buffered saline
- SNP:
-
sodium nitroprusside
- TBA:
-
2-thiobabituric acid
- TEP:
-
1,1,3,3-tetraethoxypropane
References
D. J. Selkoe (1996) ArticleTitleThe molecular pathology of Alzheimer’s disease Neuron. 6 487–498
R. D. Terry (1996) ArticleTitleNeuropathological changes in Alzheimer's disease Prog. Brain Res. 101 193–203
M. Eddleston L. Mucke (1993) ArticleTitleMolecular profile of reactive astrocytes: Implications for their role in neurologic disease Neuroscience 54 15–36 Occurrence Handle10.1016/0306-4522(93)90380-X Occurrence Handle1:CAS:528:DyaK3sXltFCnsbo%3D Occurrence Handle8515840
H. J. Kim W. H. Lee C. H. Yoon J. C. Jeong K. S. Nam H. M. Kim Y. K. Choo M. C. Lee C. H. Kim (2001) ArticleTitleBombycis corpus extract prevents amyloid-beta-induced cytotoxicity and protects superoxide dismutase activity in cultured rat astrocytes Pharmacol. Res. 43 11–16 Occurrence Handle1:STN:280:DC%2BD3MzitFOrug%3D%3D Occurrence Handle11207060
S. I. Lee (1986) Clinical application of oriental medicinal herbs Sungbo Publishing Co. Seoul, Korea 453–497
J. J. Kang (2000) Study on the inhibitory effect of Boyanghwanotang dementia. Thesis of Ph.D., Dongguk University Graduate School Seoul, Korea
S. T. Jin (1991) Suksilbirok Traditional Chinese Medicine Publishing Co. Beijing, China 296–297
X. Chen Y. Jia B. Wang (1992) ArticleTitleInhibitory effects of the extract of Bombusae concretio salicea on monoamine oxidase in aged mice Chung Kuo Chung Yao Tsa Chih. 17 107–110 Occurrence Handle1:STN:280:DyaK3s%2FjvFGlsw%3D%3D Occurrence Handle1418524
W. H. Lee J. C. Chung (1998) ArticleTitleEffects of Bombusae concretio salicea on amyloid-β-induced neuronal cell toxicity and lipid peroxidation in cultured rat astrocytes J. Kor. Oriental Internal Medicine 19 381–391
C. Holscher (1997) ArticleTitleNitric oxide, the enigmatic neuronal messenger: Its role in synaptic plasticity Trends Neurosci. 20 298–303 Occurrence Handle1:CAS:528:DyaK2sXksVCjtbY%3D Occurrence Handle9223222
Z. Huang P. L. Huang N. Panahain T. Dalakara M. C. Fishman M. A. Moskowitz (1994) ArticleTitleEffects of cerebral ischemia in mice deficient in neuronal nitric oxide synthase Science 265 1883–1885 Occurrence Handle1:CAS:528:DyaK2cXmtVagur4%3D Occurrence Handle7522345
A. Bhardwaj F. J. Northington R. N. Ichord D. F. Hanley R. J. Traystman R. C. Koehler (1997) ArticleTitleCharacterization of ionotropic glutamate receptor-mediated nitric oxide production in vivo in rats Stroke 28 850–857 Occurrence Handle1:CAS:528:DyaK2sXislyhsL8%3D Occurrence Handle9099207
C. Nathan Q. W. Xie (1994) ArticleTitleNitric oxide synthases: roles, tolls, and controls Cell 78 915–918 Occurrence Handle10.1016/0092-8674(94)90266-6 Occurrence Handle1:CAS:528:DyaK2cXmsV2jsLg%3D Occurrence Handle7522969
B. M. Choi H. O. Pae S. I. Jang Y. M. Kim H. T. Chung (2002) ArticleTitleNitric oxide as a pro-apoptotic as cell as anti-apoptotic modulator J. Bichem. Mol. Biol. 35 116–126 Occurrence Handle1:CAS:528:DC%2BD38XhtlWmu7w%3D
K. M. Kim K. M. Peter Y. G. Kim Kwon S. K. Bai W. D. Nam Y. M. Kim (2002) ArticleTitleRegulation of apoptosis by nitrosative stress J. Biochem. Mol. Biol. 35 127–133 Occurrence Handle1:CAS:528:DC%2BD38XhtlWmu70%3D Occurrence Handle16248977 Occurrence Handle10.1017/S0140525X00022871
M. A. Marletta (1994) ArticleTitleNitric oxide synthase: Aspects concerning structure and catalysis Cell 78 927–930 Occurrence Handle10.1016/0092-8674(94)90268-2 Occurrence Handle1:STN:280:DyaK2M%2FgslOlsQ%3D%3D Occurrence Handle7522970
J. Garthwaite C. L. Boulton (1995) ArticleTitleNitric oxide signaling in the central nervous system Annu. Rev. Physiol. 57 683–706 Occurrence Handle10.1146/annurev.ph.57.030195.003343 Occurrence Handle1:CAS:528:DyaK2MXksVeqsbo%3D Occurrence Handle7539993
H. Y. Yun V. L. Dawson T. M. Dawson (1996) ArticleTitleNeurobiology of nitric oxide Crit. Rev. Neurobiol. 10 291–316 Occurrence Handle1:CAS:528:DyaK2sXmtVajsA%3D%3D Occurrence Handle8978984
C. Iadecola (1997) ArticleTitleBright and dark sides of nitric oxide in ischemic brain injury Trends Neurosci. 20 132–139 Occurrence Handle10.1016/S0166-2236(96)10074-6 Occurrence Handle1:CAS:528:DyaK2sXhsFanu78%3D Occurrence Handle9061868
E. M. Schuman D. V. Madison (1994) ArticleTitleNitric oxide and synaptic function Annu. Rev. Neurosci. 17 153–183 Occurrence Handle10.1146/annurev.ne.17.030194.001101 Occurrence Handle1:CAS:528:DyaK2cXivFCls7g%3D Occurrence Handle7516125
S. W. Levision K. D. McCarthy (1991) Astroglia in culture G. Banker K Goslin (Eds) Culturing nerve cells MIT Press Cambridge, MA 309–336
S. H. Kim Y. H. Suh (1996) ArticleTitleNeurotoxicity of a carboxyl-terminal fragment of the Alzheimer’s amyloid precursor protein J. Neurochem. 67 1172–1182 Occurrence Handle1:CAS:528:DyaK28XltlKktbo%3D Occurrence Handle8752124
Y. Kotani S. Matsuda T. C. Wen M. Sakanaka J. Tanaka N. Maeda K. Kondon S. Ueno A. Sano (1996) ArticleTitleA hydrophilic peptide comprising 18 amino acid residues of the prosaposin sequence has neurotrophic activity in vitro and in vivo J. Neurochem. 66 2197–2200 Occurrence Handle1:CAS:528:DyaK28XisVSrsb4%3D Occurrence Handle8780053
A. Mitani Y. Andou S. Matsuda K. Kataoka (1991) ArticleTitleTransient forebrain ischemia of three-minute duration consistently induces severe neuronal damage in field CA1 of the hippocampus in the normothermic gerbil Neurosci. Lett. 131 171–174 Occurrence Handle10.1016/0304-3940(91)90606-T Occurrence Handle1:STN:280:DyaK387gslersw%3D%3D Occurrence Handle1762691
P. A. Glascott SuffixJr. E. Gilfor J. L. Farber (1995) ArticleTitleRelationship of the metabolism of vitamin C and E in cultured hepatocytes treated with tert-butyl hydroperoxide Mol Pharmacol. 48 80–88 Occurrence Handle1:CAS:528:DyaK2MXntFakurg%3D Occurrence Handle7623778
A. Sano S. Matsuda T. C. Wen Y. Kotani K. Kondoh S. Ueno Y. Kakimoto H. Yoshimura M. Sakanaka (1994) ArticleTitleProtection by prosaposin against ischemia-induced learning disability and neuronal loss Biochem. Biophys. Res. Commun. 204 994–1000 Occurrence Handle10.1006/bbrc.1994.2558 Occurrence Handle1:CAS:528:DyaK2MXhsVeitrk%3D Occurrence Handle7980569
E. Morishita M. Masuda M. Nagao Y. Yasuda R. Sasaki (1997) ArticleTitleErythropoietin receptor is expressed in rat hippocampal and cerebral cortical neurons, and erythropoietin prevents in vitro glutamate-induced neuronal death Neuroscience 76 105–116 Occurrence Handle1:CAS:528:DyaK28Xns1Wqu70%3D Occurrence Handle8971763
D. S. Bredt S. H. Snyder (1990) ArticleTitleIsolation of nitric oxide synthetase, a calmodulin-requiring enzyme Proc. Natl. Acad. Sci. USA 87 682–685 Occurrence Handle1:CAS:528:DyaK3cXhtlGjt70%3D Occurrence Handle1689048
B. K. Siesjo (1988) ArticleTitleHistorical overview. Calcium, ischemia, and death of brain cells Ann. NY. Acad. Sci. 522 638–661 Occurrence Handle1:STN:280:DyaL1c3jvFemsQ%3D%3D Occurrence Handle2454060
E. S. Furfine M. F. Harmon J. E. Paith R. G. Knowles M. Salter R. J. Kiff C. Duffy R. Hazelwood J. A. Oplinger E. P. Garvey (1994) ArticleTitlePotent and selective inhibition of human nitric oxide synthases. Inhibition by non-amino acid isothioureas J. Biol. Chem. 269 26677–26683 Occurrence Handle1:CAS:528:DyaK2cXmslGjtrc%3D Occurrence Handle7523410
M. K. Sharma G. R. Buettner (1993) ArticleTitleInteraction of vitamin C and vitamin E during free radical stress in plasma; An ESR study Free Radical Biol. Med. 14 649–653 Occurrence Handle10.1016/0891-5849(93)90146-L Occurrence Handle1:CAS:528:DyaK3sXltleit7o%3D
H. G. Shertzer G. L. Bannenberg H. Zhu R. M. Liu P. Moldeus (1994) ArticleTitleThe role of thiols in mitochondrial susceptibility to iron and tert-butyl hydroperoxide-mediated toxicity in cultured mouse hepatocytes Chem. Res. Toxicol. 7 358–366 Occurrence Handle10.1021/tx00039a013 Occurrence Handle1:CAS:528:DyaK2cXivFWlsLo%3D Occurrence Handle8075367
B. X. Wang X. H. Zhao S. B. Qi S. Kaneko M. Hattori T. Namba Y. Nomura (1988) ArticleTitleEffects of repeated administration of deer antler extract on biochemical changes related to aging in senescence-accelerated mice Chem. Pharm. Bull. 36 2587–2592 Occurrence Handle1:STN:280:DyaL1M7psFeqtA%3D%3D Occurrence Handle3240480
B. X. Wang X. H. Zhao S. B. Qi X. W. Yang S. Kaneko M. Hattori T. Namba Y. Nomura (1988) ArticleTitleStimulating effect of deer antler extract on protein synthesis in senescence accelerated mice in vivo Chem. Pharm. Bull. 36 2593–2598 Occurrence Handle1:STN:280:DyaL1M7psFeqtQ%3D%3D Occurrence Handle2467755
K. Kohno S. Ohta K. Kohno Y. Kumon A. Mitani S. Sakaki K. Kataoka (1996) ArticleTitleNitric oxide synthase inhibitor reduces delayed neuronal death in gerbil hippocampal CA1 neurons after transient global ischemia without reduction of brain temperature or extracellular glutamate concentration Brain Res. 738 275–280 Occurrence Handle10.1016/S0006-8993(96)00794-9 Occurrence Handle1:CAS:528:DyaK28Xms1ejsr8%3D Occurrence Handle8955523
J. L. Dinerman T. M. Dawson M. J. Schell A. Snowman S. H. Snyder (1994) ArticleTitleEndothelial nitric oxide synthase localized to hippocampal pyramidal cells: Implications for synaptic plasticity Proc. Natl. Acad. Sci. USA 91 4214–4218 Occurrence Handle1:CAS:528:DyaK2cXktVGksb0%3D Occurrence Handle7514300
D. B. Kantor M. Lanzrein J. Stary G. M. Sandoval W. B. Smith B. M. Sullivan N. Davidson E. M. Schuman (1996) ArticleTitleA role for endothelial NO synthase in LTP revealed by adenovirus-mediated inhibition and rescue Science 274 1744–1748 Occurrence Handle10.1126/science.274.5293.1744 Occurrence Handle1:CAS:528:DyaK28Xntlyquro%3D Occurrence Handle8939872
S. Murphy M. L. Simmons L. Agullo A. Garcia D. L. Feinstein E. Galea D. J. Reis D. Minc-Golomb J. P. Schwartz (1993) ArticleTitleSynthesis of nitric oxide in CNS glial cells Trends Neurosci. 16 323–328 Occurrence Handle1:CAS:528:DyaK3sXlslOqu74%3D Occurrence Handle7691008
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Chung, TW., Koo, BS., Choi, EG. et al. Neuroprotective Effect of a Chuk-Me-Sun-Dan on Neurons from Ischemic Damage and Neuronal Cell Toxicity. Neurochem Res 31, 1–9 (2006). https://doi.org/10.1007/s11064-005-9006-6
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DOI: https://doi.org/10.1007/s11064-005-9006-6