• 대한물리의학회지
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• 제5권2호
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• pp.265-272
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• 2010

Purpose : This study was investigated the effect of electroacupuncture stimulation on the change of blood biochemical components in the rat spinal cord injury(SCI) damaged by the 6-hydroxydopamine. Methods : SCI model rats were damaged in L1-L2 injected with 6-hydroxydopamine. The thirty Sprague-Dawley adult male rats were randomly divided into normal group, control group and electroacupuncture group. Experimental groups were applied as electroacupuncture(Es-160, ITO, Japan) for 15minutes during the low frequency(2 Hz) stimulation to zusanli. The enzyme concentration levels analysis of the hematological changes were measured of Glutamate Oxaloacetate Transaminase(GOT), Glutamate Pyruvate Transaminase(GPT), Lactate dehydrogenase(LDH) and motor function recovery change was evaluated by the rota-rod test. Results : This study were as follow : The concentration of GOT, LDH in experimental group was lower than control group(p<.05). The experimental group showed increase of motor function recovery more in compared to control group(p<.05). Conclusion : The results of this study showed that electroacupuncture to zusanli point have an effect on functional recovery after the 6-hydroxydopamine induced SCI in rats.

• 약학회지
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• 제32권1호
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• pp.40-49
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• 1988

There is evidence that brain norepinephrine may play a role in experimentally induced seizures in animals. Thus the present experiments were undertaken in an attempt to explore the role of brain norepinephrine in anticonvulsant activity of clonazepam. 6-Hydroxydopamine was given to newborn rats and PTZ-induced seizures were tested $70{\sim}90$ days after birth and the rats were killed for determination of brain norepinephrine 8 days after the seizure test. Depletion of norepinephrine in the rat brain significantly potentiated the PTZ-induced convulsions and antagonized the effect of clonazepam on clonic seizures, tonic seizures and the number of seizures, but the latency to the seizure and the mortality has not been altered. However the 6-hydroxydopamine-induced antagonism of anticonvulsant action was surmountable by increasing the dose of clonazepam. These results show that brain norepinephrine may play an important role in seizure susceptability as well as in the anticonvulsant activity of clonazepam in rats.

• 약학회지
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• 제41권1호
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• pp.86-93
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• 1997

Even though both N-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine have been widely used to establish the experimental model for dopaminergic neuronal ce ll death. mechanisms underlying this phenomenon have not been firmly explored. To investigate how these dopaminergic neurotoxins induce neuronal cell death, murine dopaminergic neuronal cell line, MN9D cells were treated with various concentration of either 6-hydroxydopamine or active form of MPTP, N methyl-4-phenylpyridinium (MPP$^+$). Treatment of cells with 5-100 uM 6-hydroxydopamine resulted in apoptotic cell death whereas cell death induced by 5~50 uM MPP$^+$ was not demonstrated typical apoptotic characteristics such as cell shrinkage, apoptotic body and nuclear condensation. Cell death induced by 6-hydroxydopamine was partially blocked in the presence of antioxidants including soluble form of vitamin E or desferrioxamine suggesting that generation of oxidative stress may be associated with 6-hydroxydopamine-induced cell death in MN9D cells. In contrast, MPP$^+$-induced cell death was not blocked by treatment with any of antioxidants tested. As previously demonstrated that MPP$^+$ caused metabolic alterations such as glucose metabolism, removal of glucose from the medium partially inhibited MPP$^+$-induced cell death suggesting excessive cycles of glycolysis may be associated with MPP$^+$-induced cell death. Taken together, these studies demonstrate that two types of dopaminergic neurotoxins recruit distinct neuronal cell death pathways.

• 한국생명과학회:학술대회논문집
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• 한국생명과학회 2006년도 제47회 학술심포지움 및 추계국제학술대회
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• pp.77.1-77.1
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• 2006

• 생약학회지
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• 제40권4호
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• pp.351-356
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• 2009

Many isoquinoline alkaloids including berberine lower dopamine content by reducing tyrosine hydroxylase (TH) activity and aggravate L-DOPA-induced cytotoxicity in PC12 cells. In this study, the effects of berberine on 6-hydroxydopamine (6-OHDA)-induced cytotoxicity in PC12 cells and on unilateral 6-OHDA-lesioned rat models were investigated. Berberine at 10-30 ${\mu}M$ did not affect cell viability in PC12 cells. However, berberine at concentrations higher than $50{\mu}M$ caused cytotoxicity at 24 h. Berberine (10-50 ${\mu}M$) also enhanced 6-OHDA (10-50 ${\mu}M$)-induced cytotoxicity at 24 h compared to 6-OHDA alone with an apoptotic process. In addition, treatment with berberine (5 and 30 mg/kg, i.p.) for three weeks showed a dopaminergic cell loss in substantia nigra of 6-OHDA-lesioned rats: 30 mg/kg berberine was more intensive cytotoxic. The levels of dopamine were also decreased by berberine (5 and 30 mg/kg) in the ipsilateral substantia nigra of 6-OHDA-lesioned rats. These results suggest that berberine aggravated 6-OHDA-induced cytotoxicity in PC12 cells and treatment with berberine (5 and 30 mg/kg) in 6-OHDA-lesioned rats also enhanced the degeneration of dopaminergic cell death and the decrease in dopamine levels in substantia nigra. Therefore, the long-term L-DOPA therapeutic patients with isoquinoline compounds including berberine may need to be checked for the adverse symptoms.

• 약학회지
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• 제31권2호
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• pp.82-91
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• 1987

The effect of neurotoxic compound 6-hydroxydopamine (6-OHDA) on the change in blood pressure and contractile response of Vas deference by centrally acting agents has been studied in normal and DOCA-salt induced hypertensive rats. The treatment of neonatal rats with 6-OHDA (2$\times$100mg, 250mg Kg$^{-1}$s.c) significantly inhibited the antihypertensive and relaxant effects of Vas deference of clonidine(100$\mu\textrm{g}$ Kg$^{-1}$iv.). The simultaneous administration of desipramine with clonidine into neonatal rats decreased the antihypertensive response of clonidine although treated did not affect the relaxative response of Vas deference. Furthermore, the antihypertensive and relaxant responses of clonidine were reduced by the neonatal rats with 6-OHDA regardless of the administration of desipramine. When neonatal rats were administered with 6-OHDA, the development of DOCA-salt hypertension was prevented. These results suggest that 6-OHDA, clonidine and desipramine hada significant effect on the development and the inhibition of central hypertension mediating the central adrenergic neuron due to their affinity to the central nervous system.

• 약학회지
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• 제60권2호
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• pp.92-99
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• 2016

Parkinson's disease (PD) is one of the representative neurodegenerative movement disorders with the selective loss of dopaminergic neurons in the substantia nigra. 6-Hydroxydopamine (6-OHDA) is widely used as an experimental model system to mimic PD and has been reported to cause neuronal cell death via oxidative and/or nitrosative stress. Therefore, daily intake of dietary or medicinal plants which fortifies cellular antioxidant capacity can exert neuroprotective effects in PD. In the present study, we have investigated the protective effect of Korean red ginseng (KRG) against 6-OHDA-induced nitrosative death in C6 glioma cells. Treatment of C6 cells with 6-OHDA decreased cell viability and increased expression of inducible nitric oxide synthase, production of nitric oxide as well as peroxynitrite, and formation of nitrotyrosine. 6-OHDA led to apoptotic cell death as determined by decreased Bcl-2/Bax, phosphorylation of JNK, activation of caspase-3, and cleavage of PARP. Conversely, pretreatment of C6 cells with KRG attenuated 6-ODHA-induced cytotoxicity, apoptosis, and nitrosative damages. To further elucidate the molecular mechanism of KRG protection against 6-OHDA-induced nitrosative cell death, we have focused on the cellular self-defense molecules against exogenous noxious stimuli. KRG treatment up-regulated heme oxygenase-1 (HO-1), a key antioxidant enzyme essential for cellular defense against oxidative and/or nitrosative stress via activation of Nrf2. Taken together, these findings suggest KRG may have preventive and/or therapeutic potentials for the management of PD.

• 대한수의학회지
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• 제54권1호
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• pp.1-6
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• 2014

Parkinson's disease is known to exhibit progressive degeneration of the dopaminergic neurons in the substantia nigra via inhibition of glutathione metabolism. It is well known that 6-Hydroxydopamine (6-OHDA) induces Parkinson's disease-like symptoms, while resveratrol (3,5,4'-trihydroxystilbene) has been shown to have anti-inflammatory and antioxidant effects. In the present study, we investigated the neuroprotective effects of resveratrol, a phytoalexin found in grapes and various plants, on 6-OHDA-induced cell damage to the SH-SY5Y human neuroblastoma cell line. Resveratrol (5 and 10 ${\mu}M$) inhibited 6-OHDA (60 ${\mu}M$)-induced cytotoxicity in SH-SY5Y cells and induced a reduction of the number of apoptotic nuclei caused by 6-OHDA treatment. Additionally, the total apoptotic rate of cells treated with both resveratrol (10 ${\mu}M$) and 6-OHDA (60 ${\mu}M$) was less than that of 6-OHDA treated cells. Resveratrol also dose-dependently (1, 5 and 10 ${\mu}M$) scavenged reactive oxygen species (ROS) induced by 6-OHDA in SH-SY5Y cells and prevented depletion of glutathione in response to the 6-OHDA-induced cytotoxicity in the glutathione assay. Overall, these results indicate that resveratrol exerts a neuroprotective effect against 6-OHDA-induced cytotoxicity of SH-SY5Y cells by scavenging ROS and preserving glutathione.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.196.2-197
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• 2003

Parkinson's disease (PO) is a widespread neurodegenerative disorder. Even though PD has been studied in many aspects, it is still unknown the molecular signaling mechanisms linking reactive oxygen species (ROS) and neuronal apoptosis in PD. A better understanding of cellular mechanisms that occur in Parkinson's disease is essential for development of new therapies. In this study we investigated the signaling molecules involved in neuronal apoptosis induced by 6-hydroxydopamine (6-OHDA) in human SK-N-SH neuroblastoma cells as a model cellular system. (omitted)

• 생약학회지
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• 제42권4호
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• pp.341-347
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• 2011

The neuroprotective effects of herbal ethanol extracts from Gynostemma pentaphyllum (GP-EX) in 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease treated with L-DOPA were investigated. Rats were prepared for the Parkinson's disease model by 6-OHDA-lesioning for 14 days. The rats were then treated with L-DOPA (10 and 20 mg/kg) with or without the oral administration of GP-EX (30 mg/kg, daily) for 28 days. L-DOPA (20 mg/kg) treatment for 28 days enhanced dopaminergic neuronal cell death in 6-OHDA-lesioned rat groups, but L-DOPA (10 mg/kg) did not. However, the oral administration of GP-EX (30 mg/kg) for 28 days ameliorated the enhanced neurotoxic effects induced by chronic L-DOPA treatment in 6-OHDA-lesioned rat groups by increasing tyrosine hydroxylase (TH)-immunohistochemical staining and the number of TH-immunopositive cells surviving in the substantia nigra. In addition, GP-EX administration (30 mg/kg) for 28 days recovered the levels of dopamine and norepinephrine of the striatum in 6-OHDA-lesioned rat groups, which were markedly reduced by L-DOPA treatment (20 mg/kg). GP-EX (30 mg/kg) did not produce any signs of toxicity, such as weight loss, diarrhea, or vomiting in rats during the 28-day treatment period. These results suggest that GP-EX has protective functions against chronic L-DOPA-induced neurotoxic reactions in dopaminergic neurons in the 6-OHDA-lesioned rat model of Parkinson's disease. Therefore, GP-EX may be beneficial in the prevention of adverse symptoms in parkisonian patients.