• Journal of Nutrition and Health
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• v.56 no.2
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• pp.140-154
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• 2023

Purpose: Deodeok (Codonopsis lanceolata) is generally used in conventional medicines and is considered to have remedial properties to cure several diseases. However, application of the C. lanceolata bud as a novel food ingredient has not been fully explored. Hydrogen peroxide (H₂O₂) is associated with the production of oxidative damage that results in mutagenesis, carcinogenesis, and cell death. This study examines the neuroprotective effect of C. lanceolate bud extracts (CLBE) on H₂O₂-stimulated apoptosis in SH-SY5Y cells. Methods: C. lanceolata bud of length 10 to 15 cm was collected and extracted using 70% ethanol. Cytotoxicity was evaluated by the EZ-cytox reagent, measurement of lactic dehydrogenase (LDH) release and reactive oxygen species (ROS). The morphological changes of the nuclei were determined using the Hoechst 33258 dye. Enzyme activities were analyzed using the caspase activity assay kit. Related protein expressions were quantified by the Western blot immunoassay in H₂O₂-stimulated SH-SY5Y cells. Results: Cell viability, LDH release and ROS generation, demonstrated neuroprotective effects of CLBE in H₂O₂-stimulated SH-SY5Y cells. The occurrence of apoptosis in H₂O₂-stimulated cells was confirmed by caspase activity, which was increased in H₂O₂-stimulated SH-SY5Y cells compared to the unexposed group. Pretreatment of CLBE was observed to inhibit the H₂O₂-stimulated apoptosis. In addition, exposure to CLBE resulted in increased expression of the Bcl-2 (B cell lymphoma 2) protein and decreased expression of the Bax (Bcl2 associated X) protein. Conclusion: This study shows that exposure to CLBE alleviates the H₂O₂-stimulated neuronal damage in SH-SY5Y cells. Our results indicate the potential application of CLBE in neurodegenerative disease therapy or prevention.

• Biomolecules & Therapeutics
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• v.31 no.1
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• pp.127-138
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• 2023

Glycogen synthase kinase-3β (GSK-3β) is an important serine/threonine kinase that implicates in multiple cellular processes and links with the neurodegenerative diseases including Alzheimer's disease (AD). In this study, structure-based virtual screening was performed to search database for compounds targeting GSK-3β from Enamine's screening collection. Of the top-ranked compounds, 7 primary hits underwent a luminescent kinase assay and a cell assay using human neuroblastoma SH-SY5Y cells expressing Tau repeat domain (Tau_RD) with pro-aggregant mutation ΔK280. In the kinase assay for these 7 compounds, residual GSK-3β activities ranged from 36.1% to 90.0% were detected at the IC₅₀ of SB-216763. In the cell assay, only compounds VB-030 and VB-037 reduced Tau aggregation in SH-SY5Y cells expressing ΔK280 Tau_RD-DsRed folding reporter. In SH-SY5Y cells expressing ΔK280 Tau_RD, neither VB-030 nor VB-037 increased expression of GSK-3α Ser21 or GSK-3β Ser9. Among extracellular signal-regulated kinase (ERK), AKT serine/threonine kinase 1 (AKT), mitogen-activated protein kinase 14 (P38) and mitogenactivated protein kinase 8 (JNK) which modulate Tau phosphorylation, VB-037 attenuated active phosphorylation of P38 Thr180/ Tyr182, whereas VB-030 had no effect on the phosphorylation status of ERK, AKT, P38 or JNK. However, both VB-030 and VB-037 reduced endogenous Tau phosphorylation at Ser202, Thr231, Ser396 and Ser404 in neuronally differentiated SH-SY5Y expressing ΔK280 Tau_RD. In addition, VB-030 and VB-037 further improved neuronal survival and/or neurite length and branch in mouse hippocampal primary culture under Tau cytotoxicity. Overall, through inhibiting GSK-3β kinase activity and/or p-P38 (Thr180/Tyr182), both compounds may serve as promising candidates to reduce Tau aggregation/cytotoxicity for AD treatment.

• Journal of Physiology & Pathology in Korean Medicine
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• v.36 no.6
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• pp.209-212
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• 2022

We recently reported that Gastrodia elata extracts (GEE) had an effects to protect against lipopolysaccharide-induced cognitive impairment in vivo model. In this study, we investigated the neuroprotective effects and the mechanism of action of GEE in hydrogen peroxide (H₂O₂)-induced cell death of SH-SY5Y human neuroblastoma cell. The SH-SY5Y cells were divided into five groups, including control(non-treated group), 100 μM H₂O₂, 100, 200, 500 ㎍/㎖ GEE+ 100 μM H₂O₂ groups. Pre- and co-treatment with GEE prevented cell death induced by 100 μM H₂O₂ for 24 h in SH-SY5Y cells. Our findings also showed that anti-oxidants enzymes (Cu/Zn superoxide dismutase, Mn superoxide dismutase, catalase) were up-regulated by 100 μM H₂O₂. But GEE suppressed H₂O₂-induced anti-oxidants enzymes decrease in a dose-dependent manner. Treatment with GEE also inhibited phosphorylation of eukaryotic initiation factor-2α (eIF-2α) and p38 by H₂O₂. Taken together, the neuroprotective effects of GEE in terms of recovery of antioxidant enzymes expression, down-regulation of eIF-2α and p38 phosphorylation, and inhibition of cell death are associated with reduced oxidative stress in SH-SY5Y cells.

• Nutrition Research and Practice
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• v.17 no.5
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• pp.899-916
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• 2023

BACKGROUND/OBJECTIVES: Oxidative stress is a fundamental neurodegenerative disease trigger that damages and decimates nerve cells. Neurodegenerative diseases are chronic central nervous system disorders that progress and result from neuronal degradation and loss. Recent studies have extensively focused on neurodegenerative disease treatment and prevention using dietary compounds. Heseperetin is an aglycone hesperidin form with various physiological activities, such as anti-inflammation, antioxidant, and antitumor. However, few studies have considered hesperetin's neuroprotective effects and mechanisms; thus, our study investigated this in hydrogen peroxide (H₂O₂)-treated SH-SY5Y cells. MATERIALS/METHODS: SH-SY5Y cells were treated with H₂O₂ (400 µM) in hesperetin absence or presence (10-40 µM) for 24 h. Three-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assays detected cell viability, and 4',6-diamidino-2-phenylindole staining allowed us to observe nuclear morphology changes such as chromatin condensation and apoptotic nuclei. Reactive oxygen species (ROS) detection assays measured intracellular ROS production; Griess reaction assays assessed nitric oxide (NO) production. Western blotting and quantitative polymerase chain reactions quantified corresponding mRNA and proteins. RESULTS: Subsequent experiments utilized various non-toxic hesperetin concentrations, establishing that hesperetin notably decreased intracellular ROS and NO production in H₂O₂-treated SH-SY5Y cells (P < 0.05). Furthermore, hesperetin inhibited H₂O₂-induced inflammation-related gene expression, including interluekin-6, tumor necrosis factor-α, and nuclear factor kappa B (NF-κB) p65 activation. In addition, hesperetin inhibited NF-κB translocation into H₂O₂-treated SH-SY5Y cell nuclei and suppressed mitogen-activated protein kinase protein expression, an essential apoptotic cell death regulator. Various apoptosis hallmarks, including shrinkage and nuclear condensation in H₂O₂-treated cells, were suppressed dose-dependently. Additionally, hesperetin treatment down-regulated Bax/Bcl-2 expression ratios and activated AMP-activated protein kinase-mammalian target of rapamycin autophagy pathways. CONCLUSION: These results substantiate that hesperetin activates autophagy and inhibits apoptosis and inflammation. Hesperetin is a potentially potent dietary agent that reduces neurodegenerative disease onset, progression, and prevention.

• Radiation Oncology Journal
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• v.24 no.4
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• pp.272-279
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• 2006

$\underline{Purpose}$: This study investigated the influence of irradiation and cisplatin on PrxI & PrxII expression and on their survival rates (SR) in SK-N-BE2C and Rat2 cell lines. $\underline{Materials\;and\;Methods}$: The amount of PrxI & PrxII production with or without N-acetyl-L-cysteine (NAC) pretreatment was studied using a western blot after 20 Gy irradiation to determine the degree of inhibition of ROS accumulation. In addition, the amount of PrxI & PrxII production after cisplatin and after combination with cisplatin and 20 Gy irradiation was studied. The SRs of the cell lines in SK-N-BE2C and Rat 2 cells, applied with 20 Gy irradiation only, with various concentrations of cisplatin and with the combination of both, were studied. The 20 Gy irradiation-only group and the combination group were each subdivided according to NAC pretreatment, and corresponding SRs were observed at 2, 6, 12 and 48 hours after treatment. $\underline{Results}$: Compared with the control group, the amount of PrxI in SK-N-BE2C increased up to 60 minutes after irradiation and slightly increased after irradiation with NAC pretreatment 60 minutes. It did not increase in Rat2 after irradiation regardless of NAC pretreatment. PrxII in SK-N-BE2C and Rat2 was not increased after irradiation regardless of NAC pretreatment. The amounts of PrxI and PrxII in SK-N-BE2C and Rat2 were not increased either with the cisplatin-only treatment or the combination treatment with cisplatin and irradiation. SRs of irradiation group with or without NAC pretreatment and the combination group with or without NAC pretreatment were compared with each other in SK-N-BE2C and Rat2. SR was significantly high for the group with increased amount of PrxI, NAC pretreatment and lower the cisplatin concentration. SR of the group in SK-N-BE2C which had irradiation with NAC pretreatment tended to be slightly higher than the group who had irradiation without NAC pretreatment. SR of the group in Rat2 which had irradiation with NAC pretreatment was significantly higher than that the group which had irradiation without NAC pretreatment. Compared to the combination group, the irradiation-only group revealed statistically significant SR decrease with the maximal difference at 12 hours. However, at 48 hours the SR of the combination group was significantly lower than the irradiation-only group. $\underline{Conclusion}$: PrxI is suggested to be an antioxidant enzyme because the amount of PrxI was increased by irradiation but decreased pretreatment NAC, a known antioxidants. Furthermore, cisplatin may inhibit PrxI production which may lead to increase cytotoxicity of irradiation. The expression of PrxI may play an important role in cytotoxicity mechanism caused by irradiation and cisplatin.

• Pediatric Infection and Vaccine
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• v.18 no.1
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• pp.40-47
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• 2011

Purpose : Norovirus infection, a common cause of community-acquired gastroenteritis, can also lead to severe illness in immunocompromised patients. We investigated clinical manifestations of norovirus infection in pediatric cancer patients. Methods : Stool specimens were collected from pediatric patients with gastrointestinal symptoms between November 2008 and September 2009 at Samsung Medical Center, Seoul, Korea. Norovirus infection was identified by reverse-transcription polymerase chain reaction (RT-PCR). A retrospective chart review was performed in pediatric cancer patients who were diagnosed with norovirus infection. Results : Ten patients were diagnosed with norovirus infection by RT-PCR in stool samples. The median age was 0.83 years (range 0.25-5.5 years) and the male to female ratio was 1.5:1 (6 males and 4 females). Underlying diseases were hematologic malignancies (4/10, 40%), neuroblastoma (4/10, 40%), and brain tumors (2/10, 20%). Three patients were infected before hematopoietic cell transplantation (HCT) and four patients after HCT. All patients had diarrhea (10/10, 100%), with a median frequency of diarrhea of 8.5 times/day (range 4-22 times/day). Median virus shedding duration was 72.5 days (range 19-299 days). Four patients with pneumatosis intestinalis were conservatively treated with bowel rest and total parenteral nutrition. One patient with severe diarrhea and bloody stool had concomitant chronic gut graft-versus-host disease (GVHD). Norovirus infection-related mortality was not observed. Conclusion : Norovirus infection can cause significant clinical manifestations with prolonged viral shedding in immunocompromised patients. Norovirus should be considered in pediatric cancer patients with severe gastrointestinal symptoms.

• Korean Journal of Food Science and Technology
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• v.50 no.5
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• pp.517-527
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• 2018

The current study investigated in vitro anti-diabetic and neuroprotective effects of the ethyl acetate fraction in Actinidia arguta sprouts (EFAS), on $H_2O_2$ and high glucose-induced cytotoxicity in human neuroblastoma MC-IXC cells. EFAS had high total phenolic and total flavonoid contents. An assessment of 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activity of EFAS, as well as its potential for inhibiting malondialdehyde production, indicated that EFAS may possess significant antioxidant properties. EFAS exerted inhibitory effects on ${\alpha}-glucosidase$ via glycemic regulation which forms advanced glycation end products. In addition, EFAS exhibited significant acetylcholinesterase inhibitory effects. Moreover, EFAS displayed protective effects against $H_2O_2$ and high glucose-induced cell death, and inhibited the generation of reactive oxygen species in MC-IXC cells. Finally, the main physiological compound of EFAS was identified via high performance liquid chromatography as a rutin.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.7
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• pp.938-947
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• 2016

Antioxidant activities and neuroprotective effects of ethyl acetate fraction from Dendropanax morbifera (EFDM) against high glucose-induced oxidative stress and neurotoxicity were investigated to confirm their physiological activities. An 80% ethanolic extract of D. morbifera showed the highest contents of total phenolic compounds as well as 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) and 1,1-diphenyl-2-picrylhydrazyl radical scavenging activities. The extract was fractionated using several solvents, and the ethyl acetate fraction showed the highest activities in ferric reducing/antioxidant power and malondialdehyde inhibitory assays. To evaluate the neuroprotective effect based on antioxidant activities, cell viability was assessed using PC12 and MC-IXC cells in $H_2O_2$- and high glucose-induced cytotoxic assays, respectively. EFDM evidently showed neuroprotective effects in all cells (neuron-like PC12 cells and human brain-originated neuroblastoma MC-IXC cells). Inhibitory effect of the extract on acetylcholinesterase (AChE) as an acetylcholine-hydrolyzing enzyme was performed to examine the effect on cognitive function. EFDM presented an AChE inhibitory effect. Finally, high-performance liquid chromatography analysis showed that the major phenolic compound of EFDM is probably a rutin.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.10
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• pp.1458-1469
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• 2015

This study was carried out to investigate the nitrite scavenging activities (NSA) of nine kinds of wild vegetables in a $NaNO_2$ model system and nitrite of Chinese cabbage as well as the inhibitory effect of kimchi containing a mixture of wild vegetables (MWV) with nitrite scavenging activity on brain neuronal cell death. NSA was higher at pH 1.2 than pH 4.2 in all samples. NSA of extracts from sprouts of Oenothera laciniata and Aster scaber (AS) was above 90% at pH 1.2. AS, Codonopsis lanceolate (CL), Adenophora triphylla (AT), Platycodon grandiflorum (PG), and Taraxacum officinale (TO) extracts showed significantly higher levels of NSA than those from other extracts at pH 4.2. CL, AT, PG, and TO extracts showed high NSA on nitrite of Chinese cabbage. In addition, the effects of MWV on antioxidant and brain neuronal cell death induced by oxidative stress were investigated in human brain neuroblastoma SK-N-SH cells. MWV extract attenuated $H_2O_2$-induced cell death and reactive oxygen species (ROS) generation in SK-N-SH cells. MWV extract showed significantly higher DPPH radical scavenger activity when compared to normal kimchi extract. MWV extract showed an inhibitory effect on brain neuronal cell death against oxidative stress by antioxidant activities.

• Radiation Oncology Journal
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• v.27 no.4
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• pp.189-193
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• 2009

Purpose: To report on the changes in the patterns of care and survival over time for esthesioneuroblastoma. Materials and Methods: We retrospectively analyzed 42 previously untreated and histologically confirmed esthesioneuroblastoma patients seen between March 1989 and June 2007. According to Kadish's classification, 3 patients (7%) were stage A, 6 (14%) at stage B, and 33 (79%) at stage C. Of the 33 Kadish C patients, 19 and 14 patients were treated from 1989 through 2000 and from 2001 through 2007, respectively. Treatment included surgical resection, radiotherapy, chemotherapy, or a combination of these methods. Chemotherapy was administered to 8 of 19 patients (42%) seen from 1989 through 2000, whereas all of the 14 patients seen from 2001 through 2007 received chemotherapy (p<0.001). No patient was treated by three-dimensional conformal radiotherapy (3D-CRT) from 1989 through 2000, however 8 of 14 patients (67%) seen from 2001 through 2007 underwent 3D-CRT (p<0.001). The median follow-up time for surviving patients was 6.5 years (range, 2.2~15.8 years). Results: The 5-year overall survival (OS) and progression-free survival (PFS) rates for the entire cohort were 53% and 39%, respectively. The 5-year OS was 100% for Kadish stages A or B and 39% for stage C (p=0.007). For patients with stage C disease who were treated from 1989 to 2000 and from 2001 to 2007, the 5-year OS rate was 26% and 59% (p=0.029), respectively and the corresponding 5-year PFS rate was 16% and 46% (p=0.001), respectively. Intraorbital extension and treatment era (1989~2000 vs. 2001~2007) were found as independent factors for OS and PFS in a multivariate analyses. Conclusion: The results of this study suggest that treatment era, which features a distinction in treatment modality and technique with the introduction of 3D-CRT, may be the cause of improved OS and PFS in Kadish stage C patients. To achieve better outcomes for patients with Kadish stage C, combined chemoradiotherapy, especially 3D-CRT, is recommended in addition to surgery.