• The Korea Journal of Herbology
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• v.35 no.1
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• pp.1-8
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• 2020

Objectives : This study was conducted to evaluate the effects of Corni Fructus, the dried fruits of Cornus officinalis Sieb., on unilateral common carotid artery occlusion (UCCAO) in mouse model. Methods : The Corni Fructus used in the experiment was extracted with anhydrous methanol, then filtered and freeze-dried. C57BL/6 mice used in the experiments were conducted left UCCAO surgery to set up UCCAO rodent model for mice. The mice were divided into five groups for evaluate the effect of methanol extract of Corni Fructus (COM) on UCCAO induced ischemic brain injury. The expression levels of nitric oxide in cerebrum and serum, body weight change were measured. To determine the effect of UCCAO and COM administration on brain neurons, morphological changes of the cerebrum through a microscope was conducted. And western blot was performed to confirm the underlying mechanism of neuroprotective effect of COM administration. Results : COM administered UCCAO groups (CO50, CO150, and CO500) had no significant effects on nitric oxide production in ipsilateral hemisphere proteins and sera. The CO500, 500 mg/kg COM administration, attenuated UCCAO-induced p38 inflammatory signaling pathway and inflammatory mediators such as iNOS and COX-2. The CO500 group showed resilient morphological changes of hippocampus neuronal cells about brain damage caused by decreased flow of blood. These group also showed decreased inflammation and cellular stress response in neuronal cells. Conclusions : From these results, COM has a neuroprotective property via moderating inflammatory factors and cellular stress inducing factors in brain cells.

• BMB Reports
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• v.45 no.9
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• pp.532-537
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• 2012

P18, a member of the INK4 family of cyclin-dependent kinase inhibitors, is a tumor suppressor protein and plays a key cell survival role in a variety of human cancers. Under pathophysiological conditions, the INK4 group proteins participate in novel biological functions associated with neuronal diseases and oxidative stress. Parkinson's disease (PD) is characterized by loss of dopaminergic neurons, and oxidative stress is important in its pathogenesis. Therefore, we examined the effects of PEP-1-p18 on oxidative stress-induced SH-SY5Y cells and in a PD mouse model. The transduced PEP-1-p18 markedly inhibited 1-methyl-4-phenyl pyridinium-induced SH-SY5Y cell death by inhibiting Bax expression levels and DNA fragmentation. Additionally, PEP-1-p18 prevented dopaminergic neuronal cell death in the substantia nigra of a 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine-induced PD mouse model. These results indicate that PEP-1-p18 may be a useful therapeutic agent against various diseases and is a potential tool for treating PD.

• Journal of Ginseng Research
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• v.47 no.2
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• pp.199-209
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• 2023

Background: Due to the interrupted blood supply in cerebral ischemic stroke (CIS), ischemic and hypoxia results in neuronal depolarization, insufficient NAD+, excessive levels of ROS, mitochondrial damages, and energy metabolism disorders, which triggers the ischemic cascades. Currently, improvement of mitochondrial functions and energy metabolism is as a vital therapeutic target and clinical strategy. Hence, it is greatly crucial to look for neuroprotective natural agents with mitochondria protection actions and explore the mediated targets for treating CIS. In the previous study, notoginseng leaf triterpenes (PNGL) from Panax notoginseng stems and leaves was demonstrated to have neuroprotective effects against cerebral ischemia/reperfusion injury. However, the potential mechanisms have been not completely elaborate. Methods: The model of middle cerebral artery occlusion and reperfusion (MCAO/R) was adopted to verify the neuroprotective effects and potential pharmacology mechanisms of PNGL in vivo. Antioxidant markers were evaluated by kit detection. Mitochondrial function was evaluated by ATP content measurement, ATPase, NAD and NADH kits. And the transmission electron microscopy (TEM) and pathological staining (H&E and Nissl) were used to detect cerebral morphological changes and mitochondrial structural damages. Western blotting, ELISA and immunofluorescence assay were utilized to explore the mitochondrial protection effects and its related mechanisms in vivo. Results: In vivo, treatment with PNGL markedly reduced excessive oxidative stress, inhibited mitochondrial injury, alleviated energy metabolism dysfunction, decreased neuronal loss and apoptosis, and thus notedly raised neuronal survival under ischemia and hypoxia. Meanwhile, PNGL significantly increased the expression of nicotinamide phosphoribosyltransferase (NAMPT) in the ischemic regions, and regulated its related downstream SIRT1/2/3-MnSOD/PGC-1α pathways. Conclusion: The study finds that the mitochondrial protective effects of PNGL are associated with the NAMPT-SIRT1/2/3-MnSOD/PGC-1α signal pathways. PNGL, as a novel candidate drug, has great application prospects for preventing and treating ischemic stroke.

• Korean Journal of Acupuncture
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• v.40 no.3
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• pp.90-98
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• 2023

Objectives : Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide and is characterized by the loss of the dopaminergic neurons in the substantia nigra (SN). In a previous in vitro study, we demonstrated that Sihogyeji-tang (SG), Sihosogan-tang (SS), and Sihocheonggan-tang (SC) have the potential to be candidate medicines for PD. This study aimed to compare the neuroprotective effect of SG, SS, and SC using 1-methyl-4-phenyl-1,2,3,6-tetrahydrophridine (MPTP)-induced PD mouse model. Methods : Eight-week-old male C57BL/6 mice were intraperitoneally administered with 30 mg/kg of MPTP for 5 days and orally administered SG, SS and SC for 12 days from the first MPTP injection. Motor function was assessed using the pole test and the rotarod test. Dopaminergic neuronal survival in the SN and striatum was evaluated through tyrosine-hydroxylase immunohistochemistry. Results : MPTP administration resulted in behavioral impairment and dopaminergic neuronal death in the SN and striatum. In the pole test, treatment with SG, SS, and SC alleviated the MPTP-induced motor dysfunction on day 5 and 12. In the rotarod test, SS and SG alleviated the MPTP-induced motor dysfunction on day 5, while only SS showed improvement on day 12. SS and SG significantly protected dopaminergic neurons in the SN from MPTP toxicity, and all three compounds (SG, SS, and SC) showed significant protection in the striatum. Notably, SS demonstrated superior efficacy in suppressing MPTP-induced motor dysfunction and dopaminergic neuronal death compared to SG and SC. Conclusions : These findings suggest that SS is the most effective formula among SG, SS, and SC for PD, indicating its potential role in the treatment of PD.

• Journal of the Korean Applied Science and Technology
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• v.37 no.3
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• pp.418-428
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• 2020

The aim of this study was to investigate the effect of resistance exercise(RE) on beta-amyloid(Aβ) metabolism, neuronal cell death, and cognitive function in the transgenic mice model of Alzheimer's disease(AD). Fourteen transgenic(tg) mice and fourteen non-transgenic(non-tg) mice were divided into four groups: (1)non-tg-control(NTC, n=7) (2)non-tg-RE(NTRE, n=7) (3)tg-control(TC, n=7), and (4)tg-RE(TRE, n=7). The groups with RE were performed to progressive RE on ladder equipment for 8 weeks. The groups with RE were performed to progressive RE on ladder equipment for 8 weeks. After then, the cognitive function was measured by using the water maze test, and Aβ metabolism-related proteins, neuronal cell death, and SIRT1/PGC-1α pathway were also measured. Here, we found escape latency and time were significantly increased in the TC compared to the NTC group, but it was significantly reduced in the TRE group, indicating RE may ameliorate cognitive dysfunction. Next, we found an increased in Aβ protein of TC compared to NTC, but it was significantly reduced in the TRE group following RE. In neuronal cell death, Bcl-2 was also significantly decreased and Bax was significantly increased in the TC compared to the NTC group, but RE can increase Bcl-2 and reduce Bax, which may elevate the ratio of Bcl-2/Bax. We further found a decrease in the level of ADAM10 and RARβ protein was significantly increased whereas increased in ROCK1 and BACE1 expression level was significantly reduced following RE in the TRE compared to the TC group. In addition, the level of SIRT1/PGC-1α proteins was decreased in the TC group compared to NTC group, but, these markers were significantly increased in the TRE group following RE. Therefore, our finding indicated that RE may ameliorate cognitive deficits by reducing Aβ protein and neuronal cell death via regulating SIRT1/PGC-1α, amyloidogenic pathway, and non-amyloidogenic pathway, which may play a role in an effective strategy for AD.

• Journal of Korean Academy of Nursing
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• v.40 no.4
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• pp.580-588
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• 2010

Purpose: The purpose of this study was to examine effects of decreased locomotor activity on mass, Type I and II fiber cross-sectional areas of ipsilateral and contralateral hindlimb muscles 21 days after establishing the Parkinson's disease rat model. Methods: The rat model was established by direct injection of 6-hydroxydopamine (6-OHDA, 50 ${mu}g$) into the left substantia nigra after stereotaxic surgery. Adult male Sprague-Dawley rats were assigned to one of two groups; the Parkinson's disease group (PD; n=17) and a sham group (S; n=8). Locomotor activity was assessed before and 21 days after the experiment. At 22 days after establishing the rat model, all rats were anesthetized and soleus and plantaris muscles were dissected from both ipsilateral and contralateral sides. The brain was dissected to identify dopaminergic neuronal death of substantia nigra in the PD group. Results: The PD group at 21 days after establishing the Parkinson's disease rat model showed significant decrease in locomotor activity compared with the S group. Weights and Type I and II fiber cross-sectional areas of the contralateral soleus muscle of the PD group were significantly lower than those of the S group. Conclusion: Contralateral soleus muscle atrophy occurs 21 days after establishing the Parkinson's disease rat model.

• Journal of Integrative Natural Science
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• v.5 no.1
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• pp.6-12
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• 2012

c-Jun N-terminal kinase-3 (JNK-3) has been identified as a promising target for neuronal apoptosis and has the effective therapeutic for neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, and other CNS disorders. Herein, we report the essential structural and chemical parameters for JNK-3 inhibitors utilizing comparative molecular field similarity indices analysis (CoMSIA) using the derivatives of 3,5-disubstituted quinolines. The best predictions were obtained CoMSIA model (q2=0.834, r2=0.987) and the statistical parameters from the generated 3D-QSAR models were indicated that the data are well fitted and have high predictive ability. The resulting contour map from 3D-QSAR models might be helpful to design novel and more potent JNK3 derivatives.

• Laboraroty Animal Research
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• v.34 no.4
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• pp.203-210
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• 2018

Stress severely disturbs physiological and mental homeostasis which includes adult neurogenesis in hippocampus. Neurogenesis in hippocampus is a key feature to adapt to environmental changes and highly regulated by multiple cellular signaling pathways. The primary cilium is a cellular organelle, which acts as a signaling center during development and neurogenesis in adult mice. However, it is not clear how the primary cilia are involved in the process of restraint (RST) stress response. Using a mouse model, we examined the role of primary cilia in repeated and acute RST stress response. Interestingly, RST stress increased the number of ciliated cells in the adult hippocampal dentate gyrus (DG). In our RST model, cell proliferation in the DG also increased in a time-dependent manner. Moreover, the analysis of ciliated cells in the hippocampal DG with cell type markers indicated that cells that were ciliated in response to acute RST stress are neurons. Taken together, these findings suggest that RST stress response is closely associated with an increase in the number of ciliated neurons and leads to an increase in cell proliferation.

• Journal of Korean Biological Nursing Science
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• v.22 no.4
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• pp.223-231
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• 2020

Purpose: The purpose of this study was to investigate the effects of taro extract on brain resilience in in vitro Parkinson's disease model induced by 6-hydroxydopamine (6-OHDA). Methods: To induce a neuroinflammatory reaction and the in vitro Parkinson's disease model, SH-SY5Y cells were stimulated with lipopolysaccharide (LPS) and 6-OHDA, respectively. After that, cells were treated with at various concentrations (1, 5, and 10 mg/mL) of taro extract. Then nitric oxide (NO) production, inducible nitric oxide synthase (iNOS), interleukin (IL)-6, synaptophysin (SYP) and growth associated protein (GAP)-43 messenger ribonucleic acid (mRNA) expression level were measured. Results: Taro extract significantly suppressed LPS-induced NO production. Meanwhile, iNOS and IL-6 mRNA expression decreased in a dose-dependent manner. In addition, taro increased the mRNA expression of SYP and GAP-43 mRNA. Conclusion: These findings indicate that taro played an important role in brain resilience by inhibiting neuronal cell death and promoting neurite outgrowth, synaptogenesis, and neural plasticity. The results of this study suggest that taro may contribute to the prevention of neurodegenerative disease and become a new and safe therapeutic strategy for Parkinson's disease.

• Journal of Korean Neurosurgical Society
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• v.55 no.3
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• pp.125-130
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• 2014

Objective : This study was conducted to elucidate neuroprotective effect of carnosine in early stage of stroke. Methods : Early stage of rodent stroke model and neuroblastoma chemical hypoxia model was established by middle cerebral artery occlusion and antimycin A. Neuroprotective effect of carnosine was investigated with 100, 250, and 500 mg of carnosine treatment. And antioxidant expression was analyzed by enzyme linked immunosorbent assay (ELISA) and western blot in brain and blood. Results : Intraperitoneal injection of 500 mg carnosine induced significant decrease of infarct volume and expansion of penumbra (p<0.05). The expression of superoxide dismutase (SOD) showed significant increase than in saline group in blood and brain (p<0.05). In the analysis of chemical hypoxia, carnosine induced increase of neuronal cell viability and decrease of reactive oxygen species (ROS) production. Conclusion : Carnosine has neuroprotective property which was related to antioxidant capacity in early stage of stroke. And, the oxidative stress should be considered one of major factor in early ischemic stroke.