• YAKHAK HOEJI
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• v.46 no.6
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• pp.433-440
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• 2002

The protective efficacy of Rheum palmatum water extract on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism was studied in C57BL/6 mice. In order to demonstrate neuroprotective effect of R. palmatum extract, animals were administered intraperitoneally with the water extract (100 or 200 mg/kg/day) for 14 days, and MPTP (10 mg/kg/day) was injected subcutaneously into the mice for the first 6 consecutive days from the beginning 1 hr before R. palmatum extract treatment. All animals were measured the several neurobiochemical markers such as dopamine level and monoamine oxidase B (MAO-B) activity in various regions of brain. The treatment of mice with R. palmatum extract was confirmed recovery effect on MAO-B activity in the cerebellum and the cerebral cortex. R. palmatum extract was attenuated the MPTP-induced depletion of substantia nigra dopamine. The contents of MDA, a marker of lipid peroxidation, in brain tissues (cerebellum and cerebral cortex mitochondria) were decreased significantly by R. palmatum extract. These results suggest that R. palmatum water extract plays an effective role in attenuating MPTP-induced neurotoxicity in mice. This protective effect of R. palmatum might be estimated the result from the inhibitory activity on monoamine oxidase B and the enhancement of antioxidant activity.

• Toxicological Research
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• v.9 no.2
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• pp.217-224
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• 1993

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a well-known dopamine neuron-specific toxin. But the involvement of oxidative damage in the pathogenesis of MPTP-induced parkinsonism is still uncertain. In this study, by using 2',7',-dichlorofluorescin diacetate(DCFH-DA) that detects intracellular oxidative processes, the effect of MPTP on dichlorofluorescein fluorescence in dissociated cells from fetal rat mesencephalon in culture was investigated. At 7th day in culture, cells were loaded with DCFH-DA, and exposed to 1 mM MPTP or MPP+. MPTP induced dichlorofluorescein-fluorescence which was peaked at 3 min and mostly faded away 30 min after MPTP treatment.

• Korean Journal of Acupuncture
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• v.25 no.1
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• pp.155-164
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• 2008

목 적 : 본 연구의 목적은 양릉천 침 처치 시 C57BL/6 생쥐의 중뇌 흑질에 위치한 도파민성 신경세포 사멸 억제 효과를 조직화학 염색법을 이용하여 Tyrosine hydroxylase(TH)와 laminin의 발현으로 관찰하고자 한다. 실험방법 : 실험에 이용한 동물은 C57BL/6 생쥐로, 매일 25mg/kg의 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)를 5일간 주사하였고, 매일 MPTP 주사한 뒤 2시간 후에 양릉천에 침치료를 시행하였으며 MPTP 주사를 종료한 뒤 침치료는 7일동안 계속 시행하였다. 마지막 MPTP 주사 7일 후에 동물을 희생하여 뇌를 적출하고 고정하였다. 침효과를 확인하기 위해 Thyrosine hydroxylase(TH), laminin의 발현 변화 정도를 조직염색화학법으로 이용하여 확인하였다. 각 그룹간의 유의성 검증은 one-way ANOVA를 이용하였다. 결 과 : 도파민성 신경세포 선택적인 신경독소인 MPTP에 대한 양릉천 침처치에 의한 신경보호 효과를 도파민신경세포의 표지자인 TH 발현을 면역화학조직염색법으로 관찰하였다. 대조군에 비해 MPTP 처치 군의 신경세포 사멸이 유의적으로 감소하였고(P <0.05), MPTP + 침처치 군에서 증가되는 양상을 확인하였다 (P <0.05). 또한 도파민성 신경세포내에 존재하는 laminin의 발현정도 역시 대조군보다 MPTP 처치 군에서 유의적으로 감소하였고, MPTP + 침처치 군에서 증가되는 양상을 확인하였다 (P <0.05). 결 론 : MPTP에 의한 도파민성 신경세포 손상에 대한 양릉천 침처치의 신경보호 효과는 세포외 기질중의 하나인 laminin의 발현 정도를 조절하여 비롯되는 것으로 사료된다.

• Korean Journal of Acupuncture
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• v.23 no.4
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• pp.169-176
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• 2006

Objectives : This study was designed to compare the effects of tonification and sedation methods of Liver Meridian in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease mice model. Methods : We injected MPTP (30 mg/kg, i.p.) or saline for 5 consecutive days. Acupuncture treatments were given to the mice with MPTP at LR8 and LR4 to tonify Liver Meridian (Liver+) or LR4 and LR2 to sedate it (Liver-) for 12 day. At the 12th day after first injection, mice were perfused, and then tyrosine hydroxylase (TH)-immunohistochemistry was performed in substantia nigra (SN) of their brains. After counting the number of TH-positive neurons, we compared their numbers among experimental groups. Results : The number of TH-positive neurons of Liver+ group was significantly increased compared to that of MPTP group in the SN. That of Liver-group was also increased more than MPTP group, but not significantly. Conclusions : Tonifying Liver Meridian might be effective therapeutic tools for the neuroprotection in subchronic MPTP-induced mice model.

• Journal of Oriental Neuropsychiatry
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• v.23 no.1
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• pp.129-143
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• 2012

Objectives : To evaluate the neuroprotective effects of the essential oil from Sohaphwangwon (SH), a Chinese traditional medicinal prescription in a Parkinson's disease mouse model. Methods : 1. The neuroprotective effect of SH on primary neuronal cells was examined by using 1-methyl-4-phenylpyridinium ion (MPP+). 2. The neuroprotective effect of SH was examined in a Parkinson's disease mouse model. C57BL/6 mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30 mg/kg/day), intraperitoneal (i.p.) for 5 days. SH inhalation was applied before MPTP treatment for 7 days and continued until 12 days after the first MPTP treatment. 3. To find out the intracellular target signal molecule(s) regarding the neuroprotective effect of SH essential oil, brain-derived neurotropic factor (BDNF) and synaptic protein SNAP25 were examined by Western blot analysis. Results : 1. MPP+ induced a concentration-dependent decrease in cell viability. However, in the presence of 3 and 5 ug/ml of SH, MPP+-induced cell death was significantly reduced. 2. SH inhalation in MPTP mice led to the restoration of behavioral impairment and rescued tyrosine hydroxylase (TH)-positive dopaminergic neurodegeneration. 3. In SH / MPTP mice, BDNF and SNAP25 increased. Conclusions : This experiment suggests that the neuroprotective effect of SH essential oil is mediated by the expression of BDNF. Furthermore, SH essential oil may serve as a potential preventive or therapeutic agent regarding Parkinson's disease.

• The Journal of Korean Medicine
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• v.29 no.4
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• pp.94-103
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• 2008

Objectives: The aim of this study was to determine whether celastrol, the triterpenoid component of Celastrus orbiculatus, offers neuroprotection against Parkinson's disease (PD) in mice administered 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine(MPTP). Methods: We examined how celastrol affected MPTP-induced neuronal loss of tyrosine hydroxylase (TH)-positive dopaminergic neurons in substantia nigra pars compacta (SNpc) in the midbrain of mice. C57BL/6J mice were divided into four groups: (1) saline-saline, (2) saline-celastrol, (3) MPTP-saline, and (4) MPTP-celastrol. The mice were injected intraperitoneally (i.p.) with four administrations of MPTP (18mg/kg) at 2 h intervals and then i.p. administered celastrol (3mg/kg) two times at 12 h after last celastrol administration. Expression of TH on the SNpc of brain tissues were analyzed at 7 days after the treatments by immunohistochemistry and Western blot. Results: Immunohistochemical analysis using TH antibody showed that celastrol provided significantly protective effects against MPTP-induced loss of TH-positive dopaminergic neurons in the SNpc region of the midbrain of mice. Our Western blot study also showed that celastrol significantly inhibits the MPTP-induced neuronal damage via the up-regulation of TH protein levels in MPTP mice. Conclusions: The present results suggest that it may be possible to use celastrol for the prevention of nigral degenerative disorders including PD, caused by exposure to toxic substances.

• The Korea Journal of Herbology
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• v.28 no.5
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• pp.21-28
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• 2013

Objectives : The aim of this study was to investigate the neuroprotective effects and mechanisms of Cyperi Rhizoma extracts (CRE) using in vitro and in vivo models of Parkinson's disease (PD). Methods : We evaluated the neuroprotective effect of CRE against 1-methyl-4-phenylpyridinium (MPP+) toxicity using tyrosine hydroxylase immunohistochemistry (IHC) in primary rat mesencephalic dopaminergic neurons. In addition, the effect of CRE was evaluated in mice PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). For evaluations, C57bl/6 mice were orally treated with CRE 50 mg/kg for 5 days and were injected intraperitoneally with MPTP (20 mg/kg) at 2 h intervals on the last day. To identify the CRE affects on MPTP-induced neuronal loss of dopaminergic neurons in substantia nigra pars compacta (SNpc) and striatum of mice, the behavioral tests and IHC analysis were carried out. Also, we conducted nitric oxide (NO) and tumor necrosis factor-alpha (TNF-${\alpha}$) assay in dopaminergic neurons and IHC using glial markers in SNpc of mice to assess the anti-inflammation effects. Results : In primary mesencephalic culture system, CRE protected dopaminergic cells against $10{\mu}M$ MPP+-induced toxicity at 0.2 and $1.0{\mu}g/mL$. In the behavior tests, CRE treated group showed improved motor deteriorations than those in the MPTP only treated group. CRE significantly protected striatal dopaminergic damage from MPTP-induced neurotoxicity in mice. Moreover, CRE inhibited productions of NO and TNF-${\alpha}$ in dopaminergic culture system and activation of astrocyte and microglia in SNpc of the mice. Conclusion : We concluded that CRE shows anti-parkinsonian effect by protecting dopaminergic neurons against MPP+/MPTP toxicities through anti-inflammatory actions.

• Journal of Sasang Constitutional Medicine
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• v.26 no.2
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• pp.165-179
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• 2014

Objectives To evaluate the neuroprotective effects of Hyangsayangwi-tang (HY), a Korean traditional medicinal prescription in a Parkinson's disease mouse model. Methods Four groups(each of 10 mouse per group) were used in this study. The neuroprotective effect of HY was examined in a Parkinson's disease mouse model. C57BL/6 mouse treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30mg/kg/day), intraperitoneal (i.p.) for 5 days. Slow behavioral responses and memory disorder is the major clinical symptoms of PD. In order to investigate the effect of HY on recovery of behavioral deficits and memory, we examined the motor function and memory by using Morris water maze and Forced swimming test. Ischemic mouse brain stained with TTC(2,3,5 triphenyl tetrazolium chloride) in the MPTP-induced Parkinson's disease to find out ischemia and tissue damage in mouse. The convenient, simple, and accurate high-performance liquid chromatography (HPLC) method was established for simultaneous determination of neurotransmitters in MPTP-HY group. To measure the amount of dopamine in mice brain, striatum-substantia nigra, was examined by Bradford assay. Immunohistochemistry was examined in the MPTP-induced Parkinson's disease (PD) mouse to evaluate the neuroprotective effects of Hyangsayangwi-tang on hippocampal lesion, ST and SNpc. Results and Conclusions Hyangsayangwi-tang (HY) prevents MPTP-induced loss of serotonin, hippocampus and TH-ir cell.

• Korean Journal of Acupuncture
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• v.39 no.1
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• pp.8-15
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• 2022

Objectives : Saam acupuncture is one of the indigenous therapeutic modalities in traditional Korean medicine. In this study, the neuroprotective effect of Saam acupuncture of kidney tonification was investigated using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. Methods : Twelve-week-old male C57BL/6 mice were intraperitoneally administered with 30 mg/kg of MPTP at 24-h intervals for 5 days and acupuncture stimulation at LU8, KI7, SP3 and KI3 was performed once a day for 12 days from the first MPTP injection. The pole test and the rotarod test were performed to evaluate motor function, and dopaminergic neuronal survival in the substantia nigra (SN) and striatum was evaluated using tyrosine-hydroxylase immunohistochemistry. Results : MPTP administration caused behavioral impairment and dopaminergic neuronal death in the nigrostriatal pathway. Whereas the Saam acupuncture treatment alleviated the MPTP-induced motor dysfunction and dopaminergic neuronal death in the SN and striatum. Conclusions : Saam acupuncture of kidney tonification can alleviate the MPTP-induced motor dysfunction and dopaminergic neuronal death in the nigrostriatal pathway, suggesting a possible role for acupuncture in the treatment of Parkinson's disease.

• Journal of The Korean Society of Clinical Toxicology
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• v.21 no.2
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• pp.81-91
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• 2023

Purpose: Edible insect extracts have been used as an alternative source for medicinal supplements due to their significant antioxidative and anti-inflammatory activity. Recent studies have reported that anti-microbial peptides from insects have neuroprotective effects on dopamine toxins. The purpose of this study was to investigate the protective functions of mealworm (Tenebrio molitor) extract (MWE) on N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced cellular toxicity in SH-SY5Y neuroblastoma cells. Methods: Cellular toxicity induced by the MPTP toxin and the impact of MWE on cell survival were analyzed using MTT assays. DAPI staining was performed to observe apoptotic phenomena caused by MPTP. Changes in caspase-3 activity and protein expression were observed using enzyme activity assays and western blot assays, respectively. Results: MWE exerted significant antioxidant activity, which was measured by both DPPH and ABTS radical assays, with a dose-dependent relationship. Furthermore, MWE resulted in cellular proliferation in SHSY5Y cells in a dose-dependent manner. Furthermore, MWE pretreatment significantly inhibited MPTP-induced cytotoxicity, with a dose-dependent relationship. The morphological characteristics of apoptosis and increased reactive oxygen species induced by MPTP were also significantly reduced by MWE pretreatment. Conclusion: MWE treatment significantly attenuated MPTP-induced changes in the levels of proteins associated with apoptosis, such as caspase-3 and PARP. These findings suggest that MWE exerts neuroprotective effects on human neuroblastoma SH-SY5Y cells subject to MPTP-induced dopaminergic neurodegeneration.