• Toxicological Research
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• 제23권1호
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• pp.33-38
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• 2007

Zinc is an endogenous transition metal that can be synaptically released during neuronal activity. However, zinc may contribute to the neuropathology associated with a variety of conditions. Carnosine expressed in glial cells can modulate the effects of zinc on neuronal excitability as a zinc chelator. We hypothesize that carnosine may protect against neurotoxicity of zinc in cortical neuronal cells. The cortical neuronal cells from newborn rats were prepared and exposed to zinc chloride and/or carnosine at various concentrations. Zinc at the doses of 0 to $500{\mu}M$ decreased neuronal cell viability in a dose-dependent manner. Additionally, at the concentrations of 100 and $200{\mu}M$, it significantly decreased cell viability in an exposed time-dependent manner (p < 0.05). Treatment with carnosine at the concentrations of 20 and $200{\mu}M$ significantly increased neuronal cell proliferation by approximately 14% and 20%, respectively, compared to the control (p < 0.05). At the concentrations of 100 and $200{\mu}M$ zinc, $20{\mu}M$ carnosine significantly increased the viability of neuronal cells by 18.3% and 12.1 %, and $200{\mu}M$ carnosine also increased it by 33.5% and 28.6%, respectively, compared to the normal control group (p < 0.01). These results suggest that carnosine at a physiologically relevant level may protect against zinc-mediated toxicity in neuronal cells as an endogenous neuroprotective agent.

• 대한한의학회지
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• 제39권1호
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• pp.35-43
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• 2018

Objectives: In the brain, glutamate is the most important excitable neurotransmitter in physiological and pathological conditions. However, the high level of glutamate induces neuronal cell death due to exitotoxicity and oxidative stress. The present study investigated to evaluate a possible neuroprotective effect of furosin isolated from Euphorbia helioscopia against glutamate-induced HT22 cell death. Methods: Furosin was isolated from methanol extract of Euphorbia helioscopia and examined whether it protects glutamate-induced neuronal cell death. The cell viability was determined using Ez-Cytox assay. Anti-oxidative effect of furosin was determined by DPPH scavenging activities, and the levels of intracellular reactive oxygen species (ROS) were determined by the fluorescent intensity after staining the cells with $H_2DCFDA$. To evaluate apoptotic cell death, we performed nuclear staining and image-based cytometeric analysis. Results: The cell viability was significantly increased by treatement with furosin compared with the treatment with glutamate. Furosin showed a strong DPPH radical scavenging activity ($EC50=1.83{\mu}M$) and prevented the accumulation of intra cellular ROS. Finally, the presence of 50 and $100{\mu}M$ furosin significantly the percentage of apoptotic cells compared with glutamate treatment. Conclusion: The present study found that furosin is a potent neuroprotectant against glutamate-induced oxidative stress through inhibition of apoptotic cell death induced by glutamate. Therefore, the present study suggests that furosin as a bioactive compound of E. helioscopia can be a useful source to develop a drug for the treatment of neurodegenerative diseases and acute brain injuries.

• Journal of Applied Biological Chemistry
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• 제63권4호
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• pp.357-363
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• 2020

Oxidative stress caused by the overproduction of reactive oxygen species (ROS) is known as an etiology of neurodegenerative diseases. Populus tomentiglandulosa (PT), a member of the Salicaceae family, is widely grown in Korea and has been reported to exert protective effects on cerebral ischemia by attenuating of oxidative stress and neuronal damage. In the present study, we investigated the antioxidant activity and neuroprotective effects of an ethanol extract and four fractions [n-butanol, ethyl acetate (EtOAc), chloroform, and n-hexane] of PT under in vitro and cellular systems. The extract and four fractions of PT showed 1,1-diphenyl-2-picrylhydrazyl (DPPH), •OH, and O2- radical scavenging activities in a dose-dependent manner. In particular, the EtOAc fraction of PT had the strongest DPPH, •OH, and O2- radical scavenging activities among the extract and other fractions. Therefore, we further investigated the neuroprotective effect of the EtOAc fraction of PT against oxidative stress in H2O2-induced SH-SY5Y cells. Treatment with H2O2 significantly decreased cell viability and lactate dehydrogenase (LDH) release, and it also increased the ROS levels compared to the normal group. However, treatment with the EtOAc fraction of PT significantly increased cell viability. Moreover, the EtOAc fraction of PT-treated group significantly suppressed ROS production and LDH release compared to the H2O2-induced control group. In conclusion, our findings indicated that PT had in vitro antioxidant activity and neuroprotective effects against oxidative stress. Therefore, PT could be used as a natural agent for protection against oxidative stress.

• 생약학회지
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• 제52권3호
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• pp.149-156
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• 2021

Excessive glutamate can cause oxidative stress in neuronal cells and this can be the reason for neurodegenerative disease. In this study, we investigated the protective effect of Spirulina maxima hot ethanol extract on mouse hippocampal HT22 cell of which glutamate receptor has no function. HT22 cells were pre-treated with S. maxima sample at a dose dependent manner (1, 10 and 100 ㎍/ml). After an hour, glutamate was treated. Cell viability, reactive oxygen species (ROS) accumulation, Ca²⁺ influx, decrease of mitochondrial membrane potential level and glutathione related assays were followed by then. S. maxima ethanol extract improved the cell viability by suppressing the ROS and Ca²⁺ formation, retaining the mitochondrial membrane potential level and protecting the activity of the antioxidant enzymes compared with group of vehicle-treated controls. These suggest that S. maxima may decelerate the neurodegeneration by attenuating neuronal damage and oxidative stress.

• 한국약용작물학회:학술대회논문집
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• 한국약용작물학회 2007년도 춘계학술발표회
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• pp.292-293
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• 2007

• 동의신경정신과학회지
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• 제21권2호
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• pp.125-140
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• 2010

Objectives : The purpose of this study is to examine from various angles the protective effect of Gastrodia elata Blume (GEB) against nerve cell death induced by $\beta$-amyloid by using the cell line SH-SY5Y, which is commonly utilized for toxicity testing in nerve cells, and to find out its mechanism of action. Methods : To begin with, as a result of assessing the rate of cell survival by employing MTT reduction assay, the treatment with $\beta$-amyloid at different concentrations caused cytotoxicity, which was inhibited by preprocessing GEB extract. In addition, after $\beta$-amyloid was processed with the cell SH-SY5Y, apoptosis progressed, which was reduced effectively by processing GEB extract. Results : When cytotoxicity was caused by using hydrogen peroxide, a representative ROS, in order to examine the antioxidant effect of GEB, its protective effect was also observed. Apart from ROS, reactive nitrogen species (RNS) are also known to play a crucial role in nerve cell death. The treatment with the NO donor SNAP increased the production of nitric oxide and the expression of iNOS, which was also inhibited by GEB extract. Meanwhile, as an attempt to find out the mechanism of action explaining the antioxidant effect, the intracellular antioxidant enzyme expressions were measured by RT-PCR, which showed that GEB extract increased the expressions of heme oxygenase-1, GAPDH and $\gamma$-glutamate cysteine ligase. Lastly, GEB extract had a protective effect against impaired memory induced by scopolamine in animal models (in vivo). Conclusions : These findings indicate that GEB has a protective effect against the death of cranial nerve cells, suggesting possibilities for the prevention and treatment of AD.

• 동의생리병리학회지
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• 제18권1호
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• pp.236-242
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• 2004

Cerebral ischemia resulting from transient or permanent occlusion of cerebral arteries leads to neuronal cell death and eventually causes neurological impairments. Bee venom has been used for the treatment inflammatory disease. In the present study, the effects of bee venom on apoptosis and cell proliferation in the hippocampal dentate gyrus following transient global ischemia in gerbils were investigated using immunohistochemistry for cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), caspase-3, and 5-bromo-2'-deoxyuridine (BrdU). It was shown that apoptotic cell death and cell proliferation in the hippocampal dentate gyrus were significantly increased following transient global ischemia in gerbils and that treatment of bee venom suppressed the ischemia-induced increase in apoptosis and cell proliferation in the dentate gyrus. The present results also showed that 1 mg/kg bee-venom treatment suppressed the ischemia-induced increasing apoptosis, cell proliferation, and COX-2 expression in the dentate gyrus. It is possible that the suppression of cell proliferation is due to the reduction of apoptotic cell death by treatment of bee venom. In the present study, bee venom was shown to prosses anti-apoptotic effect in ischemic brain disease, and this protective effect of bee venom against ischemia-induced neuronal cell death is closely associated with suppression on caspase-3 expression.

• 대한본초학회지
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• 제23권3호
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• pp.1-9
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• 2008

Objectives : This research was performed to investigate protective effect of Sophora Subprostrata against transient global ischemic damage after 5-min two vessel occlusion. Methods : Gerbils were divided into three groups: Normal group, 5-min two vessel occlusion (2VO) group, Sophora Subprostrata administrated group after 2VO. The CCAs were occluded by microclip for 5min. Sophora Subprostrata was administrated orally(12mg/ml) for 7 days after 2VO. The histological and immunohistochemistrical analysis was performed at 72 hours and 7 days after the surgery each. For histological analysis, the brain tissue was stained with 1% cresyl violet solution and Immunohistochemistry for BAX and Bcl-2 was carried out to examine effect of Sophora Subprostrata on ischemic brain tissue. Results : The results showed that (1) Sophora Subprostrata has the protective effect against ischemia in CA1 area of the gerbil hippocampus 7 days after 5-minute occlusion, (2) the treatment of Sophora Subprostrata inhibits the expression of Bax relatively after 2VO-induced ischemia. That protective effect of the Sophora Subprostrata seems to be performed by regulating the proportion of Bax and Bcl-2 protein, (3) in hypoxia/reperfusion model using PC12 cell, the Sophora Subprostrata extract has the protective effect against ischemia in the dose of $2{\mu}/m{\ell}$ and $20{\mu}/m{\ell}$.This study suggests that Sophora Subprostrata has neuroprotective effect against neuronal damage following cerebral ischemia in vivo with a widely used experimental model of cerebral ischemia in Mongolian gerbils and that Sophora Subprostrata regulates the proportion of Bax and Bcl-2 protein following ischemia. And, Sophora Subprostrata extract has protective effects also on a hypoxia/reperfusion cell culture model using PC12 cell. Conclusions : Sophora Subprostrata has protective effects against ischemic brain damage at the early stage of ischemia.

• 동의신경정신과학회지
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• 제20권2호
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• pp.31-46
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• 2009

Objectives : This experiment was designed to investigate the effect of Gojineumja(Guzhenyinzi, GJEJ) on damaged neural tissue in cultured glial cells and in the mouse brain tissue. Methods : The effects of the GJEJ on activation of astrocytes and caspase 3-positive cell counts in cultured glial cells administered with ${\beta}$-amyloid peptide were investigated. The effects of the GJEJ on levels of glial fibrillary acidic protein(GFAP)-positive reactive astrocyets and caspase 3-positive cells in the hippocampal subfields in the rats administered with scopolamine were investigated. Results : 1. GJEJ reduced levels of activated astrocytes and caspase 3-positive cell counts in cultured glial cells administered with ${\beta}$-amyloid peptide. 2. GJEJ reduced levels of GFAP-positive reactive astrocyets and caspase 3-positive cells in the hippocampal subfields in the rats administered with scopolamine. Conclusions : The present data. suggest that GJEJ may have a protective function of neuronal and non-neuronal cells in damaged neural tissue caused by AD-like stimulations. Further studies on identification of effective molecular components of GJEJ and their interactions with damaged neural cells would be important for understanding molecular mechanism and may be further applicable for the development of therapeutic strategies.

• 한국식생활문화학회지
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• 제37권6호
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• pp.503-509
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• 2022

Methylglyoxal is a highly reactive precursor which forms advanced glycation end products (AGEs). AGEs and methylglyoxal are known to induce various diseases such as diabetes, vascular disorders, Diabetes Mellitus (DM), and neuronal disorders. Juglans regia L is an important food commonly used worldwide, having nutritious components, including phenolic compounds. Since ancient times, Juglans regia L have been differently applied by various countries for health and in diverse diseases, including arthritis, asthma, skin disorders, cancer, and diabetes mellitus. However, the effect of diabetes-induced renal damage against AGEs remains unclear. This study evaluates the anti-glycation and renal protective effects of ethanol extract of Juglans regia L against methylglyoxal-induced renal tubular epithelial cell death. Exposure to methylglyoxal resulted in reduced cell viability in NRK-52E cells, but co-treatment with Juglans regia L extracts significantly increased the cell viability. In addition, we examined the anti-glycation effect of Juglans regia L extracts. Compared to the positive control aminoguanidine and Alagebrium, treatment with Juglans regia L extracts significantly inhibited the formation of AGEs, collagen cross-linking, and breaking collagen cross-linking. Taken together, our results indicate that Juglans regia L is a potential therapeutic agent for regulating diabetic complications by exerting anti-glycation and renal protective activities.