• Title/Summary/Keyword: Neurotoxicity

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Anti-amnesic and Neuroprotective Effects of Artemisia argyi H. (Seomae mugwort) Extracts (섬애쑥 추출물의 뇌 신경세포 보호효과에 의한 학습 및 기억능력 개선 효과)

  • Ha, Gi-Jeong;Lee, Doo Sang;Seung, Tae Wan;Park, Chang Hyeon;Park, Seon Kyeong;Jin, Dong Eun;Kim, Nak-Ku;Shin, Hyun-Yul;Heo, Ho Jin
    • Korean Journal of Food Science and Technology
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    • v.47 no.3
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    • pp.380-387
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    • 2015
  • The anti-amnesic effect of Artemisia argyi H against trimethyltin (TMT)-induced learning and memory impairment and its neuroprotective effect against $H_2O_2$-inducedoxidative stress were investigated. Cognitive behavior was examined by Y-maze and passive avoidance test for 4 weeks, which showed improved cognitive functions in mice treated with the extract. In vitro neuroprotective effects against $H_2O_2$-induced oxidative stress were examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium-bromide and lactate dehydrogenase (LDH) assays. A. argyi H. extract showed protective effects against $H_2O_2$-induced neurotoxicity; moreover, LDH release into the medium was inhibited. Finally, high-performance liquid chromatography (HPLC) analysis showed that eupatilin and jaceosidin were the major phenolic compounds in A. argyi H. extract. These results suggest that A. argyi H. could be a good source of functional substances to prevent neurodegenerative diseases.

Industrial potential of domestic Zanthoxylum piperitum and Zanthoxylum schinifolium: Protective effect of both extracts on high glucose-induced neurotoxicity (국내산 초피와 산초의 산업적 활용 가능성: 고당으로 유도된 뇌신경세포 독성에 대한 추출물의 보호 효과)

  • Han, Hye Ju;Park, Seon Kyeong;Kim, Min Ji;An, Jun Woo;Lee, Se Jin;Kang, Jin Yong;Kim, Jong Min;Heo, Ho Jin
    • Korean Journal of Food Science and Technology
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    • v.52 no.3
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    • pp.274-283
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    • 2020
  • This study focused on the in vitro investigation of antioxidant and anti-diabetic activities, along with neuroprotection against high glucose-induced cytotoxicity, in order to evaluate the physiological effects of Zanthoxylum piperitum and Zanthoxylum schinifolium. The highest total phenolic content was measured in the 40% ethanolic extracts of Zanthoxylum piperitum (EZP) and Zanthoxylum schinifolium (EZS). The in vitro EZP antioxidant activity showed a relatively higher ABTS/DPPH radical scavenging activity and malondialdehyde inhibitory effect than that of EZS. The EZP inhibited carbohydrate hydrolysis (α-glucosidase and α-amylase) more efficiently than EZS in anti-diabetic tests. However, EZS showed a more efficient inhibition of advanced glycation end-products formation than EZP. In addition, both EZP and EZS effectively protected human-derived neuronal cells from high glucose-induced cytotoxicity. Finally, the physiological compounds were analyzed using UPLC IMS-QTOF/MSE, and the main EZP (quercetin-3-O-glucoside and 3-caffeoylquinic acid) and EZS (5-caffeoylquinic acid) compounds were identified as phenolic compounds.

High VPP Combination Chemotherapy for Advanced Non-Small Cell Lung Cancer (진행된 비소세포 폐암에 대한 High-VPP 복합화학요법의 효과)

  • Hong, Seok-Cheol;Han, Pyo-Seong;Lee, Jong-Jin;Cho, Hai-Jeong;Kim, Ju-Ock;Kim, Sun-Young
    • Tuberculosis and Respiratory Diseases
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    • v.40 no.4
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    • pp.367-377
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    • 1993
  • Background: The benefits of combination chemotherapy in unresectable non-small cell lung cancer remain uncertain. But, according to the recent reports, the response rates of cisplatin-based polychemotherapy regimens are higher than those of single agent. Also, the response rates of high-dose cisplatin group are higher than those of low-dose cisplatin group. In attemp to answer the question whether treatments, combination chemotherapy (high VPP) and combination chemotherapy with radiation therapy, improve survival in advanced non-small cell lung cancer, we begin to study. Method: Thirty-five patients above stage III, diagnosed histologically as non-small cell lung cancer, were enrolled. Among them, nineteen received a combination chemotherapy consisting of VP-16 & high-dose cisplatin (100 $mg/m^2$) and/or radiation therapy. The other group (16 subjects) received no therapy. To investigate the differences of survival and response rates between two groups and the side effects related to therapy, we reviewed patients' records. Results: 1) The overall objective response rate was 47%(9/19) with one complete remission. 2) In patients who received polychemotherapy and radiation therapy, the response rate was 60%(6/10) with one complete remission and survival rates of 3 months, 6 months and 12 months were 100%, 70% and 40%. 3) In patients who received polychemotherapy, the response rate was 33% (3/9) with no complete remission and survival rates of 3 months, 6 months and 12 months were 78%, 67% and 33%. 4) Overall, treated patients survived significantly longer (p<0.05) than non-treated patients (median survival 307 days versus 95 days). 5) Analysis of the various prognostic factors disclosed that good performance status, stage III and squamous cell type showed the good response rates. 6) The toxicities were nausea and/or vomiting (100%), alopecia (90%), anemia (79%), leukopenia (69%), thrombocytopenia (2%), increased creatinine (16%) and neurotoxicity (5%). Conclusion: According to above results, there are relatively good results that high VPP combination chemotherapy in advanced non-small cell lung cancer improves survival in the treated group than in the non-treated group. Thus, it is considerd that we select the patients with proper indications and treat them with effective chemotherpy and radiation therapy. But, because improvement related to high VPP ploychemotherapy is not marked in this study, it is necessary that we should investigate follow-up studies in many cases.

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Onion Beverages Improve Amyloid β Peptide-Induced Cognitive Defects via Up-Regulation of Cholinergic Activity and Neuroprotection (양파(Allium cepa L.) 음료의 콜린성 활성 증가 및 뇌신경세포 보호로 인한 Amyloid β Peptide 유도에 대한 인지장애 개선 효과)

  • Park, Seon Kyeong;Kim, Jong Min;Kang, Jin Yong;Ha, Jeong Su;Lee, Du Sang;Kim, Ah-Na;Choi, Sung-Gil;Lee, Uk;Heo, Ho Jin
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.11
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    • pp.1552-1563
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    • 2016
  • To examine the cognitive function of onion (Allium cepa L.) beverages (odourless and fortified), we analyzed in vitro neuronal cell protection against $H_2O_2$-induced cytotoxicity and performed in vivo tests on amyloid beta ($A{\beta}$)-induced cognitive dysfunction. Cellular oxidative stress and cell viability were evaluated by DCF-DA assay and MTT assay. These results show that fortified beverage resulted in better neuronal cell protection than odourless beverage at lower concentration ($0{\sim}100{\mu}g/mL$). Fortified beverage also showed more excellent acetylcholinesterase (AChE) inhibitory activity ($IC_{50}$: 4.20 mg/mL) than odourless beverage. The cognitive functions of odourless beverage and fortified beverage in $A{\beta}$-induced neurotoxicity were assessed by Y-maze, passive avoidance, and Morris water maze tests. The results show improved cognitive function in both groups treated with beverages. After in vivo tests, cholinergic activities were determined based on AChE inhibition and acetylcholine levels, and antioxidant activities were measured as SOD, oxidized glutathione (GSH)/total GSH ratio, and MDA levels in mouse brain tissue. In a Q-TOF UPLC/MS system, main compounds were analyzed as follows: odourless beverage (five types of sugars and three types of phenolics) and fortified beverages (six types of phenolics and two types of steroidal saponins).

Concurrent Cisplatin-Radiation Therapy in Locally Advanced Head & Neck Cancers - Preliminary Report - (국소진행된 두경부종양의 Cisplatin-방사선 동시병용치료 - 예비적 임상결과보고 -)

  • Kim In Ah;Choi Ihl Bhong;Cho Seung Ho;Hong Young Seon;Choi Byung Ok;Kang Young Nam
    • Radiation Oncology Journal
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    • v.19 no.3
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    • pp.205-210
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    • 2001
  • Purpose : This study tried to evaluate the effectiveness of combined treatment using radiation therapy and concurrent cisplatin as a radiosensitizer in the management of locally advanced head and neck cancer. Materials and methods : From January 1995 to August 1998, 29 evaluable patients with locally advanced head & neck cancels (AJCC stage $II\~IV$) were received curative radiation therapy $(total\;70\~75.6\;Gy/35\~42\;fractions,\;1.8\~2\;Gy/fraction)$ and concurrent cisplatin chemotherapy ($100\;mg/m^2$, D1, D22, D43). The neck dissections were peformed for residual lymphadenopathy. Follow-up ranged from 5 to 55 months (median 24 months). Results : Twenty-one $(72.4\%)$ patients achieved clinical complete responses. The partial response and minimal response rates were $17.2\%\;and\;10.4\%$, respectively. Locoregional failure rate was $27.6\%$, and included 6 patients with local failures, 4 patients with regional failures, and 2 patients with combined local and regional failures. Four of 29 patients $(13.8\%)$ developed distant metastasis. The disease free survival rate at 3 years was $60\%$. Nasopharyngeal primary tumors or complete responders showed significantly higher disease free survival rate. The grade 3 mucositis and nausea/vomiting was noted in $34.5\%$, respectively. Major prolongation of radiation therapy duration was inevitable in three patients. Twenty-one patients $(72.4\%)$ completed 3 courses of cisplatin and 5 patients received 2 courses of cisplatin. Three patients received only one course of cisplatin due to nephrotoxicity and neurotoxicity, and then changed to 5-FU regimen. Conclusions : Concurrent cisplatin-radiation therapy in locally advanced head and neck cancer showed high response rate, reasonable locoregional control, and survival rate. As expected, acute toxicities were increased, but compliance to treatment was acceptable. Assessment of the effect of the combination in this setting requires further accrual and follow-up.

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Nutritional Composition and Cytoprotective Effect of Moringa oleifera Lam. (Drumstick-tree (Moringa oleifera Lam.)의 주요 영양성분 및 추출물의 신경세포 보호 효과)

  • Jin, Su Il;Kim, Hyeon Ju;Jeong, Ji Hee;Jin, Dong Eun;Choi, Sung-Gil;Heo, Ho Jin
    • Korean Journal of Food Science and Technology
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    • v.46 no.5
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    • pp.609-615
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    • 2014
  • The cytoprotective effect of Moringa oleifera Lam. (drumstick tree) on neuronal cells was investigated to confirm the physiological benefits associated with this natural food resource. First, the drumstick tree extract was chemically analyzed to determine inherent nutritional constituents. Calcium and potassium were identified as the major mineral constituents, and palmitic acid (C16:0, 16.33%) and gadoleic acid (C20:01, 66.34%) were detected as the major fatty acids. Moreover, drumstick tree extract contained 94.78 mg/100 g vitamin E and 112.61 mg/100 g niacin. PC12 cells were used to study the cytoprotective effects of drumstick tree extract. Intracellular accumulation of reactive oxygen species was significantly reduced when $H_2O_2$ treated-neuronal cells were cultured in a medium containing the methanolic extract of drumstick tree, compared to cells treated with only $H_2O_2$. Cell viability assay using MTT showed that the extract protected cells against $H_2O_2$-induced neurotoxicity and inhibited LDH leakage from the cell membrane. Caspase assay showed that the extract exerted cytoprotective effect against apoptosis. Consequently, these data suggest that drumstick tree is a useful natural resource with positive effects on human health.

Ameliorating effect of the ethyl acetate fraction of Pteridium aquilinum on glucose-induced neuronal apoptosis (포도당으로 유도된 신경세포 손상에 대한 고사리 아세트산에틸 분획물의 개선 효과)

  • Park, Seon Kyeong;Guo, Tian Jiao;Kim, Jong Min;Kang, Jin Yong;Park, Sang Hyun;Kang, Jeong Eun;Kwon, Bong Seok;Lee, Chang Jun;Lee, Uk;Heo, Ho Jin
    • Korean Journal of Food Science and Technology
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    • v.49 no.4
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    • pp.430-437
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    • 2017
  • The protective effect of Pteridium aquilinum on high glucose-induced cytotoxicity was examined in vitro to investigate the relationship between diabetic condition and neuronal dysfunction. The ethyl acetate fraction of P. aquilinum (EFPA), with total phenolic content of 265.08 mg gallic acid equivalent/g, showed higher 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)/2,2-diphenyl-1-picrylhydrazyl radical scavenging activities and lipid peroxidation inhibitory effect than any other fraction. In addition, EFPA showed a significant reduction in the inhibitory effect on ${\alpha}$-glucosidase activity ($IC_{50}$ value=$205.26{\mu}g/mL$) compared to the acarbose positive control. The anti-oxidative effect in PC12 cells, protective effects on high glucose-induced oxidative stress in neuronal cells, and neurotoxicity were measured using 2',7'-dichlorofluorescin diacetate, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide, and lactate dehydrogenase assays, respectively. EFPA showed conspicuous inhibitory effect on cellular reactive oxygen species production and neuronal cell apoptosis. Finally, kaempferol-3-glucoside was identified as the main phenolic compound of EFPA using high performance liquid chromatography.

Preventive Characteristics of Garlic Extracts Using in vitro Model System on Alzheimer's Disease (In vitro model system을 활용한 마늘 추출물의 치매예방 특성)

  • Choi, Gwi-Nam;Kim, Ji-Hye;Kwak, Ji-Hyun;Jeong, Chang-Ho;Jeong, Hee-Rok;Shin, Jung-Hye;Kang, Min-Jung;Sung, Nak-Ju;Heo, Ho-Jin
    • Journal of agriculture & life science
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    • v.44 no.4
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    • pp.45-55
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    • 2010
  • In this study, the acetylcholinesterase (AChE) inhibition and neuronal cell protective effects of water, 100% methanol and dichlromethane extracts from garlic were investigated. We found that dichloromethane extract of garlic resulted in a dose-dependent manner on AChE inhibition ($IC_{50}$: $36.1{\mu}g/mL$). In cell viability assay using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide (MTT), cell viabilities of water, 100% methanol and dichlromethane extracts were lower (almost under 40%) than amyloid ${\beta}$ protein ($A{\beta}$)-induced neurotoxicity. Because $A{\beta}$ is also known to increase neuronal cell membrane breakdown, neuronal apoptosis was further confirmed by lactate dehydrogenase (LDH) and neutral red uptake (NRU) assay. Water extract presented relative protection against $A{\beta}$-induced membrane damage in LDH assay. However all garlic extracts showed significant problem with decrease of cell viability in NRU assay, especially at dichloromethan extract. To determine active compounds in column fractions (98:2 fraction) from dichloromethane extract which showed significant AChE inhibitory effect, we performed HPLC and LC-MS analysis. It was supposed that garlic may contain allyl methyl disulfide, diallyl monosulfide, and diallyl disulfide as active compounds.

Neuroprotective effect of fermented ginger extracts by Bacillus subtilis in SH-SY5Y cells (고초균에 의한 생강 발효 추출물의 신경세포 보호 효과)

  • Yang, Hee Sun;Kim, Mi Jin;Kim, Mina;Choe, Jeong-sook
    • Journal of Nutrition and Health
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    • v.54 no.6
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    • pp.618-630
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    • 2021
  • Purpose: The ginger rhizome (Zingiber officinale) is widely cultivated as a spice for its aromatic and pungent components. One of its constituents, 6-hydroxydopamine (6-OHDA) is usually thought to cross the cell membrane through dopamine uptake transporters, and induce inhibition of mitochondrial respiration and the generation of intracellular reactive oxygen species (ROS). This study examines the neuroprotective effect and acetylcholinesterase (AChE) inhibitory activity of fermented ginger extracts (FGEs) on 6-OHDA induced toxicity in SH-SY5Y human neuroblastoma cells. Methods: Ginger was fermented using 2 species of Bacillus subtilis, with or without enzyme pretreatment. Each sample was extracted with 70% ethanol. Neurotoxicity was assessed by applying the EZ-Cytox cell viability assay and by measuring lactic dehydrogenase (LDH) release. Morphological changes of apoptotic cell nuclei were observed by Hoechst staining. Cell growth and apoptosis of SH-SY5Y cells were determined by Western blotting and enzyme activity analysis of caspase-3, and AChE enzymatic activity was determined by the colorimetric assay. Results: In terms of cell viability and LDH release, exposure to FGE showed neuroprotective activities against 6-OHDA stimulated stress in SH-SY5Y cells. Furthermore, FGE reduced the 6-OHDA-induced apoptosis, as determined by Hoechst staining. The occurrence of apoptosis in 6-OHDA treated cells was confirmed by determining the caspase-3 activity. Exposure to 6-OHDA resulted in increased caspase-3 activity of SH-SY5Y cells, as compared to the unexposed group. However, pre-treatment with FGE inhibited the activity of caspase-3. The neuroprotective effects of FGE were also found to be caspase-dependent, based on reduction of caspase-3 activity. Exposure to FGE also inhibited the activity of AChE induced by 6-OHDA, in a dose-dependent manner. Conclusion: Taken together, our results show that FGE exhibits a neuroprotective effect in 6-OHDA treated SH-SY5Y cells, thereby making it a potential novel agent for the prevention or treatment of neurodegenerative disease.

A Randomized Phase III Study of Patients With Advanced Gastric Adenocarcinoma Without Progression After Six Cycles of XELOX (Capecitabine Plus Oxaliplatin) Followed by Capecitabine Maintenance or Clinical Observation

  • Guk Jin Lee;Hyunho Kim;Sung Shim Cho;Hyung Soon Park;Ho Jung An;In Sook Woo;Jae Ho Byun;Ji Hyung Hong;Yoon Ho Ko;Der Sheng Sun;Hye Sung Won;Jong Youl Jin;Ji Chan Park ;In-Ho Kim;Sang Young Roh;Byoung Yong Shim
    • Journal of Gastric Cancer
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    • v.23 no.2
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    • pp.315-327
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    • 2023
  • Purpose: Oxaliplatin, a component of the capecitabine plus oxaliplatin (XELOX) regimen, has a more favorable toxicity profile than cisplatin in patients with advanced gastric cancer (GC). However, oxaliplatin can induce sensory neuropathy and cumulative, dose-related toxicities. Thus, the capecitabine maintenance regimen may achieve the maximum treatment effect while reducing the cumulative neurotoxicity of oxaliplatin. This study aimed to compare the survival of patients with advanced GC between capecitabine maintenance and observation after 1st line XELOX chemotherapy. Materials and Methods: Sixty-three patients treated with six cycles of XELOX for advanced GC in six hospitals of the Catholic University of Korea were randomized 1:1 to receive capecitabine maintenance or observation. The primary endpoint was progression-free survival (PFS), analyzed using a two-sided log-rank test stratified at a 5% significance level. Results: Between 2015 and 2020, 32 and 31 patients were randomized into the maintenance and observation groups, respectively. After randomization, the median number of capecitabine maintenance cycles was 6. The PFS was significantly higher in the maintenance group than the observation group (6.3 vs. 4.1 months, P=0.010). Overall survival was not significantly different between the 2 groups (18.2 vs. 16.5 months, P=0.624). Toxicities, such as hand-foot syndrome, were reported in some maintenance group patients. Maintenance treatment was a significant factor associated with PFS in multivariate analysis (hazard ratio, 0.472; 95% confidence interval, 0.250-0.890; P=0.020). Conclusions: After 6 cycles of XELOX chemotherapy, capecitabine maintenance significantly prolonged PFS compared with observation, and toxicity was manageable. Maintenance treatment was a significant prognostic factor associated with PFS.