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Neuroprotective Effect of a Chuk-Me-Sun-Dan on Neurons from Ischemic Damage and Neuronal Cell Toxicity

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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

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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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