• International Journal of Oral Biology
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• v.42 no.2
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• pp.55-61
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• 2017

Recent studies indicate that mitochondria are an important source of reactive oxygen species (ROS) in the spinal dorsal horn. In our previous study, application of malate, a mitochondrial electron transport complex I substrate, induced a membrane depolarization, which was inhibited by pretreatment with ROS scavengers. In the present study, we used patch clamp recording in the substantia geletinosa (SG) neurons of spinal slices, to investigate the cellular mechanism of mitochondrial ROS on neuronal excitability. DNQX (an AMPA receptor antagonist) and AP5 (an NMDA receptor antagonist) decreased the malate-induced depolarization. In an external calcium free solution and addition of tetrodotoxin (TTX) for blockade of synaptic transmission, the malate-induced depolarization remained unchanged. In the presence of DNQX, AP5 and AP3 (a group I metabotropic glutamate receptor (mGluR) antagonist), glutamate depolarized the membrane potential, which was suppressed by PBN. However, oligomycin (a mitochondrial ATP synthase inhibitor) or PPADS (a P2 receptor inhibitor) did not affect the substrates-induced depolarization. These results suggest that mitochondrial substrate-induced ROS in SG neuron directly acts on the postsynaptic neuron, therefore increasing the ion influx via glutamate receptors.

• Korean Journal of Pharmacognosy
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• v.36 no.3 s.142
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• pp.195-200
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• 2005

Smilacis Chinae Radix is root of Smilax china L.. It has been known as a korean folk medicine for anti-inflammatory, anti-microbial diuresis, detoxification and relieving enteropathy as diarrhea. Reactive oxygen species(ROS) are continuously produced at a high rate as a by-product obtained in the aerobic metabolism. A major portion of living organisms has defense system as superoxide dismutase or catalase against damage produced by ROS. Several lines of evidence provided that ROS appears to cause to develop aging and various diseases. In this study, we have investigated the antioxidant activities of Smilacis Chinae Radix in order to screen the antioxidant substances from natural products. As a result, EtOAc extract of Smilacis Chinae Radix exhibited potent antioxidant effect on various antioxidant experiment. The major components of antioxidant activity were isolated from EtOAc extract of Smilacis Chinae Radix. Their structure of compounds were identified as quercetin and (-)-epicatechin by spectroscopic evidence, respectively.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.6
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• pp.519-528
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• 2019

Mitochondrial dysfunction is closely associated with reactive oxygen species (ROS) generation and oxidative stress in cells. On the other hand, modulation of the cellular antioxidant defense system by changes in the mitochondrial DNA (mtDNA) content is largely unknown. To determine the relationship between the cellular mtDNA content and defense system against oxidative stress, this study examined a set of myoblasts containing a depleted or reverted mtDNA content. A change in the cellular mtDNA content modulated the expression of antioxidant enzymes in myoblasts. In particular, the expression and activity of glutathione peroxidase (GPx) and catalase were inversely correlated with the mtDNA content in myoblasts. The depletion of mtDNA decreased both the reduced glutathione (GSH) and oxidized glutathione (GSSG) slightly, whereas the cellular redox status, as assessed by the GSH/GSSG ratio, was similar to that of the control. Interestingly, the steady-state level of the intracellular ROS, which depends on the reciprocal actions between ROS generation and detoxification, was reduced significantly and the lethality induced by $H_2O_2$ was alleviated by mtDNA depletion in myoblasts. Therefore, these results suggest that the ROS homeostasis and antioxidant enzymes are modulated by the cellular mtDNA content and that the increased expression and activity of GPx and catalase through the depletion of mtDNA are closely associated with an alleviation of the oxidative stress in myoblasts.

• Biomolecules & Therapeutics
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• v.30 no.6
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• pp.585-592
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• 2022

Treatment of triple-negative breast cancer (TNBC) has been limited due to the lack of molecular targets. In this study, we evaluated the cytotoxicity of hydroxyzine, a histamine H1 receptor antagonist in human triple-negative breast cancer BT-20 and HCC-70 cells. Hydroxyzine inhibited the growth of cells in dose- and time-dependent manners. The annexin V/propidium iodide double staining assay showed that hydroxyzine induced apoptosis. The hydroxyzine-induced apoptosis was accompanied down-regulation of cyclins and CDKs, as well as the generation of reactive oxygen species (ROS) without cell cycle arrest. The effect of hydroxyzine on the induction of ROS and apoptosis on TNBC cells was prevented by pre-treatment with ROS scavengers, N-acetyl cysteine or Mito-TEMPO, a mitochondria-targeted antioxidant, indicating that an increase in the generation of ROS mediated the apoptosis induced by hydroxyzine. Western blot analysis showed that hydroxyzine-induced apoptosis was through down-regulation of the phosphorylation of JAK2 and STAT3 by hydroxyzine treatment. In addition, hydroxyzine induced the phosphorylation of JNK and p38 MAPK. Our results indicate that hydroxyzine induced apoptosis via mitochondrial superoxide generation and the suppression of JAK2/STAT3 signaling.

• Journal of Yeungnam Medical Science
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• v.34 no.2
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• pp.174-181
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• 2017

Ferroptosis is a newly recognized type of cell death that results from iron-dependent lipid peroxidation and is different from other types of cell death, such as apoptosis, necrosis, and autophagic cell death. This type of cell death is characterized by mitochondrial shrinkage with an increased mitochondrial membrane density and outer mitochondrial membrane rupture. Ferroptosis can be induced by a loss of activity of system $X_c{^-}$ and the inhibition of glutathione peroxidase 4, followed by the accumulation of lipid reactive oxygen species (ROS). In addition, inactivation of the mevalonate and transsulfuration pathways is involved in the induction of ferroptosis. Moreover, nicotinamide adenine dinucleotide phosphate oxidase and p53 promote ferroptosis by increasing ROS production, while heat shock protein beta-1 and nuclear factor erythroid 2-related factor 2 inhibit ferroptosis by reducing iron uptake. This article outlines the molecular mechanisms and signaling pathways of ferroptosis regulation, and explains the roles of ferroptosis in human disease.

• Journal of Applied Biological Chemistry
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• v.54 no.3
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• pp.184-189
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• 2011

Polysaccharide (PS) was fractionated from hot-water extract of Artemisia iwayomogi Kitamura stems. PS showed considerably higher hydroxyl radical scavenging activity than caffeic acid and glutathione. PS showed lower superoxide anion radical scavenging activity than hydroquinone and ascorbic acid. The scavenging activity of PS on the reactive oxygen species (ROS) induced by human neutrophils with zymosan was determined by the lucigenin-enhanced chemiluminescence assay. The scavenging effect of the PS on ROS as determined by the chemiluminescence assay was about 2-fold stronger than that of ascorbic acid at the same concentration. PS significantly decreased protein carbonyl and malonaldehyde contents in UVB irradiated skin homogenates, which was comparable to glutathione at the same concentration. This result suggested that PS derived from A. iwayomogi Kitamura stems may be a potent candidate as functional compound for the protection on UVB induced skin damage in cosmetics.

• Korean Journal of Pharmacognosy
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• v.48 no.4
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• pp.289-297
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• 2017

This study was performed to investigate the effect of 8 weeks administration of snail extract on free radical formation in old female rats (27 weeks). Rats administrated orally with snail extract at the dose of 100 mg/kg, 200 mg/kg, chondroitin sulfate 10 mg/kg and 0.9% saline (control) for 8 weeks. Hematologic profiles and hepatic enzymes were all normal. Results of analysis on snail extract were naicin, Na, protein, sugar, beta-carotene, vitamin (A, B1, B2, B6, C, E), folic acid, phosphorus, lipid, K, cholesterol, chondroitin. Hepatic lipid peroxidase content was decreased, aldehyde oxidase was decreased, glutathione peroxidase and glutathione-S transferase were not changed, but xanthine oxidase, catalase and superoxidase activities were significantly increased in snail extract fed group (p<0.001). Therefore, as the result of this study, it could be expected that the administration of snail extract for 8weeks is the potential to be use as a hepatic anti-oxidative agent.

• Bulletin of the Korean Chemical Society
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• v.34 no.2
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• pp.406-410
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• 2013

Tetrahyropapaveroline (THP) is compound derived from dopamine metabolism and is capable of causing dopaminergic neurodegenerative disorder, such as Parkinson's disease (PD). The aim of this study was to evaluate the potential of THP to cause oxidative damage on the structure of cytochrome c (cyt c). Our data showed that THP led to protein aggregation and the formation of carbonyl compound in protein aggregates. THP also induced the release of iron from cyt c. Reactive oxygen species (ROS) scavengers and iron specific chelator inhibited the THP-mediated cyt c modification and carbonyl compound formation. The results of this study show that ROS may play a critical role in THP-induced cyt c modification and iron releasing of cyt c. When cyt c that has been exposed to THP was subsequently analyzed by amino acid analysis, lysine, histidine and methionine residues were particularly sensitive. It is suggested that oxidative damage of cyt c by THP might induce the increase of iron content in cells and subsequently led to the deleterious condition. This mechanism is associated with the deterioration of organs under neurodegenerative disorder such as PD.

• Journal of the Korean Applied Science and Technology
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• v.41 no.2
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• pp.447-458
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• 2024

In this study, the antioxidizing effect of 2,3-dicaffeoyl-epi-quinic acid (DEQA) was investigated. The antioxidant activity was evaluated by measuring the scavenging effect on DPPH radical and peroxynitrite and the reducing power on ferric ion. DEQA showed a scavenging effect and reducing power comparable to vitamin C used as a positive control. Also, DEQA effectively inhibited production of intracellular reactive oxygen species (ROS) in HT-1080 cells, showing the scavenging ratio of 43.8% even at 10 µM concentration of DEQA after 2 hours in HT-1080 treated with H₂O₂. In addition to this, DEQA inhibited the production of nitric oxide (NO) very effectively in Raw 264.7 cells. The above results suggest that DEQA has the potential to be developed as a natural antioxidant.

• Korean Journal of Food Science and Technology
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• v.46 no.4
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• pp.498-504
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• 2014

Allium senescens L. is perennial plant of the Liliaceae family that grows throughout Korea. In this study, we investigated the effect of Allium senescens L. methanol extracts on reactive oxygen species (ROS) production and lipid accumulation during adipogenesis. Our results indicated that 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity of Allium senescens L. methanol extracts increased in a dose-dependent manner. Allium senescens L. methanol extracts suppressed ROS production and lipid accumulation during adipogenesis. In addition, Allium senescens L. methanol extracts inhibited the mRNA expression of the pro-oxidant enzyme, such as G6PDH and lead to a reduction in the mRNA levels of the transcription factors, such as sterol regulatory element binding proteins 1c, peroxisome proliferator-activated receptor ${\gamma}$, and CCAAT/enhancer-binding proteins ${\alpha}$. These results indicate that Allium senescens L. methanol extracts inhibit adipogenesis by modulating ROS production associated with ROS-regulating genes and directly down-regulating adipogenic transcription factors.