• Korean Journal of Pharmacognosy
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• v.40 no.4
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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.

• Journal of Korean Academy of Nursing
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• v.41 no.6
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• pp.834-842
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• 2011

Purpose: The purpose of this study was to determine the effect of dehydroepiandrosterone (DHEA) on recovery of muscle atrophy induced by Parkinson's disease. Methods: The rat model was established by direct injection of 6-hydroxydopamine (6-OHDA, 20 ${\mu}g$) into the left striatum using stereotaxic surgery. Rats were divided into two groups; the Parkinson's disease group with vehicle treatment (Vehicle; n=12) or DHEA treatment group (DHEA; n=22). DHEA or vehicle was administrated intraperitoneally daily at a dose of 0.34 mmol/kg for 21 days. At 22-days after DHEA treatment, soleus, plantaris, and striatum were dissected. Results: The DHEA group showed significant increase (p<.01) in the number of tyrosine hydroxylase (TH) positive neurons in the lesioned side substantia nigra compared to the vehicle group. Weights and Type I fiber cross-sectional areas of the contralateral soleus of the DHEA group were significantly greater than those of the vehicle group (p=.02, p=.00). Moreover, extracellular signal-regulated kinase (ERK) phosphorylation significantly decreased in the lesioned striatum, but was recovered with DHEA and also in the contralateral soleus muscle, Akt and ERK phosphorylation recovered significantly and the expression level of myosin heavy chain also recovered by DHEA treatment. Conclusion: Our results suggest that DHEA treatment recovers Parkinson's disease induced contralateral soleus muscle atrophy through Akt and ERK phosphorylation.

• 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.

• Proceedings of the Ginseng society Conference
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• 1998.06a
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• pp.168-173
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• 1998

A single administration of cocaine (CO), morphine (MOR) and methamphetamine (MA) showed hyperactivity in mice. Ginseng total saponin (GTS), ginsenosides Rbl and Rgl inhibited the hyperactivity induced by the drugs. The repeated administration of CO, MOR and MA showed the development of psychological dependence showing a.: the development of conditioned place preference (CPP) in mice and the development of dopamine (DA) receptor supersensitivity showing as sensitization of the drugs. GTS and Rgl inhibited the development of not only psychological dependence but also of DA receptor supersensitivity induced by CO and MA Rbl prevented also the development of psychological dependence and DA receptor supersensitivity induced by CO and MA but not by MOR. These results suggest that the development psychological dependence induced by the drugs is closely related with the development of DA receptor supersensitivity since both phenomena were inhibited by them. Apomorphine induced climbing behavior was also inhibited by G75 but not by both of Rbl and Rgl, indicating that GTS modulate dopaminergic action at both of pre and postsynaptic sites, but both of Rbl and Rgl , only at the presynaptic site. These results suggest that active components acting at the postsynaptic site exist in GTS. In this study, it was found that GTS, ginsenosides Rbl and Rgl inhibited tyrosine hydroxylase (TH) and these components exerted inhibitory effects on both Cal' currents and $\Delta$ Cm in rat adrenal chromaffin cells. These results suggest that G75 and ginsenosides regulate catecholamine synthesis and secretion. Meanwhile, it has been demonstrated that Rbl, at high doses has more powerful inhibition of cartecholamine secretion at the presynaptic site than Rbl. Therefore, it was presumed that inhibition of morphine induced psychological dependence by Rgl, but not by Rbl results from differences in the extent of this inhibitory action on dopaminergic synthesis and secretion.

• The Korea Journal of Herbology
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• v.23 no.3
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• pp.53-60
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• 2008

Objectives : Oxidative stress has a critical role in neurodegenerative diseases. In this study, we investigated the antioxidant and neuroprotective effects of the ethanolic extract of Banryong-hwan (BRHE) in SH-SY5Y cells and primary rat mesencephalic dopaminergic neurons. Methods : To assess the antioxidant effects, we carried out 1,1-diphenyl-2-picrylhydrazyl(DPPH) free radical scavenging assay, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid)(ABTS) radical cation decolorization assay, and determination of total polyphenolic content. We evaluated the effect of BRHE treatment on neuroprotection against 6-hydroxydopamine(6-OHDA) toxicity using thiazolyl blue tetrazolium bromide(MTT) assay, nitric oxide(NO) assay, reactive oxygen species(ROS) assay in SH-SY5Y cells and tyrosine hydroxylase(TH) immunocytochemistry in primary rat mesencephalic dopaminergic neurons. Results : BRHE showed IC50 values of 328.10 ${\mu}g/mL$ and 43.12 ${\mu}g/mL$ in DPPH assay and in ABTS assay, respectively. Total polyphenolic content was 180.76 ${\mu}g/mL$. In SH-SY5Y cells, BRHE significantly attenuated the toxicity induced by 6-OHDA at the concentrations of 25-100 ${\mu}g/mL$ pre- and post- treatment in MTT assay. While 6-OHDA increased the NO and ROS contents, BRHE decreased them in a dose dependent manner. Moreover, in primary dopaminergic neuron culture, BRHE significantly protect-ed the dopaminergic cell loss against 6-OHDA toxicity up to 136% at the concentration of 75 ${\mu}g/mL$. Conclusions : These results demonstrate that BRHE has neuroprotective effect against 6-OHDA induced neurotoxicity through decreasing NO and ROS generation.

• Biomolecules & Therapeutics
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• v.27 no.4
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• pp.363-372
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• 2019

Daidzein isolated from soybean (Glycine max) has been widely studied for its antioxidant and anti-inflammatory activities. However, the protective effects of 7,8,4'-trihydroxyisoflavone (THIF), a major metabolite of daidzein, on 6-hydroxydopamine (OHDA)-induced neurotoxicity are not well understood. In the current study, 7,8,4'-THIF significantly inhibited neuronal cell death and lactate dehydrogenase (LDH) release induced by 6-OHDA in SH-SY5Y cells, which were used as an in vitro model of Parkinson's disease (PD). Moreover, pretreatment with 7,8,4'-THIF significantly increased the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) and decreased malondialdehyde (MDA) activity in 6-OHDA-induced SH-SY5Y cells. In addition, 7,8,4'-THIF significantly recovered 6-OHDA-induced cleaved caspase-3, cleaved caspase-9, cleaved poly-ADP-ribose polymerase (PARP), increased Bax, and decreased Bcl-2 levels. Additionally, 7,8,4'-THIF significantly restored the expression levels of phosphorylated c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase 1/2 (ERK 1/2), phosphatidylinositol 3-kinases (PI3K)/Akt, and glycogen synthase kinase-3 beta ($GSK-3{\beta}$) in 6-OHDA-induced SH-SY5Y cells. Further, 7,8,4'-THIF significantly increased the reduced tyrosine hydroxylase (TH) level induced by 6-OHDA in SH-SY5Y cells. Collectively, these results suggest that 7,8,4'-THIF protects against 6-OHDA-induced neuronal cell death in cellular PD models. Also, these effects are mediated partly by inhibiting activation of the MAPK and PI3K/Akt/$GSK-3{\beta}$ pathways.

• The Journal of Internal Korean Medicine
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• v.41 no.6
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• pp.1089-1099
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• 2020

Objective: The purpose of this study was to investigate the effect of cinnamon on the treatment of Parkinson's disease (PD) and to introduce its use in Korea. Method: We searched the experimental studies in electronic databases (PubMed, CNKI, Wanfang, CiNii, J-STAGE, Science ON, and OASIS) using the key search terms "cinnamic acid", "cinnamon", "cinnamomum", "Parkinson's disease", "Parkinson disease", "Parkinsonism", and "dopamine". This study only involved experimental studies (in vivo and in vitro) that adopted cinnamon as a single administration and measured indicators relating to Parkinson's disease, including parkin, tyrosine hydroxylase (TH), and dopamine. Results: A Total of 11 literature studies were selected, and they all showed that treatment with cinnamon has a neuroprotective effect. Cinnamon activated neuroprotective factors and restored neurotransmitters and it reduced the rate of oxidative stress and inflammation in neurons. As a result, cell viability was upregulated, while cell apoptosis and neurodegeneration were downregulated. Five in vivo studies, through behavioral tests, also confirmed that cinnamon recovers locomotor function in PD models. Conclusion: We identified that cinnamon is an effective neural protector and improves motor performance in behavioral testing in the experimental PD studies.

• Biomolecules & Therapeutics
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• v.29 no.5
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• pp.483-491
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• 2021

Parkinson's disease (PD) is a neurodegenerative disorder that involves the loss of dopaminergic neurons in the substantia nigra (SN). Matrix metalloproteinases-8 (MMP-8), neutrophil collagenase, is a functional player in the progressive pathology of various inflammatory disorders. In this study, we administered an MMP-8 inhibitor (MMP-8i) in Leucine-rich repeat kinase 2 (LRRK2) G2019S transgenic mice, to determine the effects of MMP-8i on PD pathology. We observed a significant increase of ionized calcium-binding adapter molecule 1 (Iba1)-positive activated microglia in the striatum of LRRK2 G2019S mice compared to normal control mice, indicating enhanced neuro-inflammatory responses. The increased number of Iba1-positive activated microglia in LRRK2 G2019S PD mice was down-regulated by systemic administration of MMP-8i. Interestingly, this LRRK2 G2019S PD mice showed significantly reduced size of cell body area of tyrosine hydroxylase (TH) positive neurons in SN region and MMP-8i significantly recovered cellular atrophy shown in PD model indicating distinct neuro-protective effects of MMP-8i. Furthermore, MMP-8i administration markedly improved behavioral abnormalities of motor balancing coordination in rota-rod test in LRRK2 G2019S mice. These data suggest that MMP-8i attenuates the pathological symptoms of PD through anti-inflammatory processes.

• The Korea Journal of Herbology
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• v.24 no.2
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• pp.87-92
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• 2009

Objectives : This study was performed to evaluate the neuroprotective effect of water extracts from Nelumbinis semen (NSW) in dopaminergic cells. Methods : We performed 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay, 2,2-azinobis3-ethyl-benzothiazoline-6-sulfonic acid (ABTS) cation scavenging assay, and determination of total polyphenolic content to examine the antioxidant effects of NSW. We also evaluated the neuroprotective effects against 6-hydroxydopamine (6-OHDA)-induced toxicity using 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyl-tetrazolium bromide assay (MIT) assay, trypan blue cytotoxicity assay, and nitric oxide assay in SH-SY5Y cells and tyrosine hydroxylase (TH) immunohistochemistry in primary rat dopaminergic neurons. Results : NSW showed $IC_{50}$ values of 184.80 and 92.90 ${\mu}$g/mL in DPPH and in ABTS assays, respectively. NSW showed 1.05% of total polyphenol contents. NSW showed protective effect against 6-0HDA-induced neurotoxicity whereas no influence on cell viability at the concentration of 1${\sim}$50 ${\mu}$g/mL. NSW reduced NO generation while 6-OHDA produced it. Moreover, it protected rat dopaminergic neurons against 6-0HDA at a dose of 1 ${\mu}$g/mL. Conclusions : These results indicated that NSW has neuroprotective effect against 6-0HDA-induced neurotoxicity through antioxidant activity in dopaminergic cell culture.

• Clinical and Experimental Reproductive Medicine
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• v.31 no.1
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• pp.19-27
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• 2004

Objective: This study was to examine the in vitro neural cell differentiation patterns of human embryonic stem (hES) cells following treatment of various neurotrophic factors [basic fibroblast growth factor (bFGF), retinoic acid (RA), brain derived neurotrophic factor (BDNF) and transforming growth factor (TGF)-$\alpha$], particulary in dopaminergic neuron formation. Methods: The hES cells were induced to differentiate by bFGF and RA. Group I) In bFGF induction method, embryoid bodies (EBs, for 4 days) derived from hES were plated onto gelatin dish, selected for 8 days in ITSFn medium and expanded at the presence of bFGF (10 ng/ml) for another 6 days followed by a final differentiation in N2 medium for 7, 14 and 21 days. Group II) For RA induction, EBs were exposed of RA ($10^{-6}M$) for 4 days and allowed to differentiate in N2 medium for 7, 14 and 21 days. Group III) To examine the effects of additional neurotrophic factors, bFGF or RA induced cells were exposed to either BDNF (10 ng/ml) or TGF-$\alpha$ (10 ng/ml) during the 21 days of final differentiation. Neuron differentiation and dopamine secretion were examined by indirect immunocytochemistry and HPLC, respectively. Results: The bFGF or RA treated hES cells were resulted in similar neural cell differentiation patterns at the terminal differentiation stage, specifically, 75% neurons and 11% glial cells. Additionally, treatment of hES cells with BDNF or TGF-$\alpha$ during the terminal differentiation stage led to significantly increased tyrosine hydroxylase (TH) expression of a dopaminergic neuron marker, compared to control (p<0.05). In contrast, no effect was observed on the rate of mature neuron (NF-200) or glutamic acid decarboxylase-positive neurons. Immunocytochemistry and HPLC analyses revealed the higher levels of TH expression (20.3%) and dopamine secretion (265.5 $\pm$ 62.8 pmol/mg) in bFGF and TGF-sequentially treated hES cells than those in $\alpha$ RA or BDNF treated hES cells. Conclusion: These results indicate that the generation of dopamine secretory neurons from in vitro differentiated hES cells can be improved by TGF-$\alpha$ addition in the bFGF induction protocol.