• Journal of Life Science
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• v.32 no.8
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• pp.647-658
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• 2022

Particulate matter (PM) is known to be involved in the onset and progression of various diseases by promoting oxidative and inflammatory reactions as air pollutants containing various small particles that are harmful. In this study, the protective efficacy of herbal medicines was evaluated in human corneal epithelial cells (hCECs) to select natural products that can protect the eye, the primary organ directly exposed to external pollutants from PM. As a result, five candid ate herbal medicines [Cheonmundong, Asparagus Rhizome; Seokchangpo, Aciru Gramineri Rhizoma; Hwangryeon, Coptidis Rhizoma; Gamgug, Chrysanthemi Indici Flos; and Geumjanhwa (Marigold flower petals)] which showed inhibitory efficacy on PM_2.5-induced cytotoxicity, were selected from among 12 candidate herbal medicines. To evaluate the antioxidant activity of these candidate substances, the reactive oxygen species (ROS) scavenging ability was investigated, and it was found that the extracts of Seokchangpo, Cheonmundong and Hwangryeon showed a significant inhibitory effect on PM_2.5-induced ROS production, which was correlated with the preservation of mitochondrial activity. In addition, it was confirmed that they could block DNA damage caused by PM_2.5 through analysis of 8-hydroxy-2'-deoxyguanosine generation and phosphorylated-H2A histone family member X (γ- H2AX) expression. Furthermore, the increase in inflammasome activity and inflammatory response in PM_2.5-treated hCECs was also canceled in the presence of these extracts. Although additional studies are needed, the results of this study will be used as primary data to find novel natural compounds that protect hCECs from PM.

• Journal of Life Science
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• v.28 no.4
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• pp.454-464
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• 2018

Black soybeans are used as food sources as well as for traditional medicines because they contain an abundance of natural phenolic compounds. In this study, total phenolic contents (TPCs) of Korean black seed coat soybean varieties Socheongja (SCJ), Socheong 2 (SC2) and Cheongja 2 (CJ2) as well as their antioxidant capacities were investigated. Among them, TPCs were abundantly present in the order of CJ2$H_2O_2$-stimulated HaCaT human keratinocytes. Our results revealed that treatment with SCJ and SC2 prior to $H_2O_2$ exposure significantly increases the viability of HaCaT cells, indicating that the exposure of HaCaT cells to SCJ and SC2 conferred a protective effect against oxidative stress. SCJ and SC2 also effectively inhibited $H_2O_2$-induced apoptotic cell death through the blocking of mitochondrial dysfunction. SCJ and SC2 also attenuated the phosphorylation of Histone H2AX. Furthermore, they effectively induced the levels of thioredoxin reductase (TrxR) 1, a potent antioxidant enzyme, which is associated with the induction of nuclear transcription factor erythroid-2-like factor 2 (Nrf2); however, the protective effects of SCJ and SC2 were significantly reversed by Auranofin, a TrxR inhibitor. These results indicate that they have protective activity through the blocking of cellular damage related to oxidative stress via the Nrf2 signaling pathway. In conclusion, our study indicated that SCJ and SC2 might potentially serve as novel agents for the treatment and prevention of skin disorders caused by oxidative stress.

• Journal of Pharmacopuncture
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• v.17 no.1
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• pp.59-69
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• 2014

Objectives: In homeopathy, it is claimed that more homeopathically-diluted potencies render more protective/curative effects against any disease condition. Potentized forms of Condurango are used successfully to treat digestive problems, as well as esophageal and stomach cancers. However, the comparative efficacies of Condurango 6C and 30C, one diluted below and one above Avogadro's limit (lacking original drug molecule), respectively, have not been critically analyzed for their cell-killing (apoptosis) efficacy against lung cancer cells in vitro, and signalling cascades have not been studied. Hence, the present study was undertaken. Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were conducted on H460-non-small-cell lung cancer (NSCLC) cells by using a succussed ethyl alcohol vehicle (placebo) as a control. Studies on cellular morphology, cell cycle regulation, generation of reactive oxygen species (ROS), changes in mitochondrial membrane potential (MMP), and DNA-damage were made, and expressions of related signaling markers were studied. The observations were done in a "blinded" manner. Results: Both Condurango 6C and 30C induced apoptosis via cell cycle arrest at subG0/G1 and altered expressions of certain apoptotic markers significantly in H460 cells. The drugs induced oxidative stress through ROS elevation and MMP depolarization at 18-24 hours. These events presumably activated a caspase-3-mediated signalling cascade, as evidenced by reverse transcriptase-polymerase chain reaction (RT-PCR), western blot and immunofluorescence studies at a late phase (48 hours) in which cells were pushed towards apoptosis. Conclusion: Condurango 30C had greater apoptotic effect than Condurango 6C as claimed in the homeopathic doctrine.

• Molecules and Cells
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• v.37 no.9
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• pp.672-684
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• 2014

The exact causes of cell death in Parkinson's disease (PD) remain unknown despite extensive studies on PD.The identification of signaling and metabolic pathways involved in PD might provide insight into the molecular mechanisms underlying PD. The neurotoxin 1-methyl-4-phenylpyridinium ($MPP^+$) induces cellular changes characteristic of PD, and $MPP^+$-based models have been extensively used for PD studies. In this study, pathways that were significantly perturbed in $MPP^+$-treated human neuroblastoma SH-EP cells were identified from genome-wide gene expression data for five time points (1.5, 3, 9, 12, and 24 h) after treatment. The mitogen-activated protein kinase (MAPK) signaling pathway and endoplasmic reticulum (ER) protein processing pathway showed significant perturbation at all time points. Perturbation of each of these pathways resulted in the common outcome of upregulation of DNA-damage-inducible transcript 3 (DDIT3). Genes involved in ER protein processing pathway included ubiquitin ligase complex genes and ER-associated degradation (ERAD)-related genes. Additionally, overexpression of DDIT3 might induce oxidative stress via glutathione depletion as a result of overexpression of CHAC1. This study suggests that upregulation of DDIT3 caused by perturbation of the MAPK signaling pathway and ER protein processing pathway might play a key role in $MPP^+$-induced neuronal cell death. Moreover, the toxicity signal of $MPP^+$ resulting from mitochondrial dysfunction through inhibition of complex I of the electron transport chain might feed back to the mitochondria via ER stress. This positive feedback could contribute to amplification of the death signal induced by $MPP^+$.

• The Journal of Internal Korean Medicine
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• v.23 no.2
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• pp.181-190
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• 2002

The water extract of Omija-tang(OMJT) has been traditionally used for treatment of ischemic heart and brain damage in oriental medicine. However, little is known about the mechanism by which the water extract of OMJT protects cells from such damage. Therefore, this study was conducted to investigate the protective mechanisms of OMJT on $H_2O_2$-induced toxicity in H9c2 cardiomyoblast cells. Treatment of $H_2O_2$ markedly induced death of H9c2 cardiomyoblast cells in a dose-dependent manner. The characteristics of $H_2O_2$-induced death of H9c2 showed apparent apoptotic features, such as DNA fragmentation. However, OMJT significantly reduced both $H_2O_2$-induced cell death and chromatin fragmentation. The decrease of Bcl-XL expression by $H_2O_2$ was inhibited by OMJT. In addition, the increase of Bcl-XS and Bax expression were also inhibited by OMJT. In particular, Fas expression, which is generally recognized as cell death inducing signal by Fas/FasL interaction, was markedly increased by $H_2O_2$ in a time-dependent manner, whereas this increase was completely prevented by OMJT. The combined treatment of OMJT and $H_2O_2$ in H9c2 cells also reduced activation of caspase-9 and caspase-3 like protease. Taken together, this study indicates that the protective effects of the water extract of OMJT against oxidative damage may be mediated by the modulation of BcI-XL/S and Bax expression by way of the regulation of mitochondrial membrane potential and caspase cascades.