• Biomolecules & Therapeutics
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• v.23 no.5
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• pp.407-413
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• 2015

Paraquat dichloride (N,N-dimethyl-4-4'-bipiridinium, PQ) is an extremely toxic chemical that is widely used in herbicides. PQ generates reactive oxygen species (ROS) and causes multiple organ failure. In particular, PQ has been reported to be an immunotoxic agrochemical compound. PQ was shown to decrease the number of macrophages in rats and suppress monocyte phagocytic activity in mice. However, the effect of PQ on macrophage cell viability remains unclear. In this study, we evaluated the cytotoxic effect of PQ on the mouse macrophage cell line, RAW264.7 and its possible mechanism of action. RAW264.7 cells were treated with PQ (0, 75, and $150{\mu}M$), and cellular apoptosis, mitochondrial membrane potential (MMP), and intracellular ROS levels were determined. Morphological changes to the cell nucleus and cellular apoptosis were also evaluated by DAPI and Annexin V staining, respectively. In this study, PQ induced apoptotic cell death by dose-dependently decreasing MMP. Additionally, PQ increased the cleaved form of caspase-3, an apoptotic marker. In conclusion, PQ induces apoptosis in RAW264.7 cells through a ROS-mediated mitochondrial pathway. Thus, our study improves our knowledge of PQ-induced toxicity, and may give us a greater understanding of how PQ affects the immune system.

• Journal of Applied Biological Chemistry
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• v.63 no.1
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• pp.89-93
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• 2020

In this study, the efficacy of melanoma cell B16F10 was investigated using the Korean native plant Oplismenus undulatifolius (OU). First, the cell viability of the extract was more than 90% when treated with 15 ㎍/mL of phenolics from OU. The results showed that melanin biosynthesis and cellular tyrosinase synthesis were inhibited by treatment with α-melanocyte-stimulating hormone-stimulated mouse melanoma cell B16F10 at a concentration of 15 ㎍/mL of phenolics for cell-line efficacy. The expression of tyrosinase, tyrosinase-related protein (TRP)-1, TRP-2, and microphthalmia transcription factor (MITF) protein was confirmed by western blot to investigate the effect of phenolics from OU on melanin biosynthesis. When treated with phenolics from OU 15 ㎍/mL, tyrosinase, TRP-1, TRP-2, and MITF decreased the protein expression level. In particular, tyrosinase, TRP-1, and MITF inhibited the production amount to a level similar to that of the non-treated normal group, indicating that the effect was excellent. Therefore, phenolics from OU acts as an inhibitor of tyrosinase, TRP-1, TRP-2, and its transcription factor MITF, and participates in melanin biosynthesis mechanism. These results suggested the potential for development as a material.

• Journal of Life Science
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• v.8 no.1
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• pp.51-59
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• 1998

The apoptosis-inducing activity of ursolic acid (UA) was examined in mouse F9 teratocarcinoma cells on the bases of biochemical and morphological characteeristics. UA, pentacyclic trierpene acid, exhibits antitumor activities including inhibition of skin tumorigenesis, induction of tumor cell differentiation and antitumor promotion. Treatment with UA showed that the decrease of cell viability was dose-dependent. UA also induced genomic DNA fragmetation, a hallmark of apoptosis, indicating that the mechanism of UA-induced F9 cell death was through apoptosis. When the morphology of the F9 cells was examined by electron microscopy, the cells treated with UA showed the charcteristic morphological features of apoptosis such as chromatin condensation and nuclear fragmentation. DNA fragmentations by UA were inhibired by cycloheximide, which suggest that de novo protein synthesis was required for DNA fragmentation by UA. Inaddition, the expression of c-jun was increased, but those of c-myc and laminin B1 were decreased during apoptosis induced by UA in F9 cells. These results suggest that UA causes an apoptosis in F9 cells. Further, the increased expression of c-jun may be involved in the UA-induced apoptosis of f9 cells.

• The Korean Journal of Food And Nutrition
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• v.27 no.3
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• pp.400-405
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• 2014

Recently, cases of Aloe vera induced-toxic hepatitis have been reported. However, the precise inflammatory effects of Aloe vera extract have not been clearly elucidated yet. In this study, the inflammatory effects and the mechanism of 70% ethanolic Aloe vera extract on liver were evaluated by in vitro assays using human hepatoma HepG2 cells. Cell viability was investigated using MTT assay at $0.001{\sim}100{\mu}g/mL$ of Aloe vera extract. To evaluate inflammatory effect of the Aloe vera extract, the secretion of pro-inflammatory cytokine Interleukin 8 (IL-8) and Macrophage colony-stimulating factor (M-CSF) were detected. Aloe vera extract did not induce cell death at concentrations of $0.001{\sim}100{\mu}g/mL$. However, Aloe vera extract significantly increased the IL-8 secretion by 15.7~25.8% and the M-CSF secretion by 36.6~61.5% at the same concentrations. These results indicate that Aloe vera extract shows an inflammation-related mild hepatotoxicity than a severe toxicity such as cell death and this hepatitis is mediated by the secretion of inflammatory cytokine IL-8 and M-CSF.

• Journal of Korea Society of Industrial Information Systems
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• v.22 no.6
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• pp.71-84
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• 2017

Over the past decade, we have witnessed Serious Debates in MISQ and Other Journals Between Two Camps that have Differing Views on the use of Causal Indicators to Measure Constructs. There is the Camp that advocates Causal Indicators (ADVOCATE) and the Camp that opposes Their Usage (OPPONENT). The Debates have been primarily centered on the OPPONENT's Argument that the Meaning of a Latent Variable is determined by its Outcome Variables. However, Little Effort has been made to Validate the ADVOCATE's Dispute (Against the OPPONENT's Arguments) that the Meaning of a Latent Variable is decided by its Causal Indicators if there is no Misspecification. Our Study precisely examines the Integrity of the Argument. For this, we empirically examine how the two Primary Psychometric Properties-Comprehensiveness and Interrelationship-of Causal Indicators Influence Theory Testing between Latent Variables through Three Different Tests (i.e., Comprehensive Test, Interrelationship Test, and Mixed Test). Conducted on Two Different Datasets, Our Analysis Consistently Reveals that Structural Path Coefficients are Hardly Sensitive to the Changes (i.e., Misspecification) in the Properties of Causal Indicators. The Discovery offers Important Evidence that the Sound Theoretical Logic of a Causal Model is not in Sync with the Empirical Mechanism of Parameter Estimation. This Underscores that a Latent Variable Formed by Causal Indicators is empirically an elusive notion that is Difficult to Operationalize. As Our Results have Significant Implications on the Integrity of Numerous IS studies which have conducted Theory or Hypothesis Testing Using Causal Indicators, we strongly advocate Open Discussions among Methodologists regarding Our Findings and Their Implications for Both Published IS Research and Future Practices.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.7
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• pp.896-902
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• 2017

In this study, we investigated citrus Kombucha (CK) produced by three different bacteria strains (Gluconacetobacter xylinus, Gluconacetobacter medellinensis, and Gluconobacter oxydans; named as CK-MOX) identified from traditional Kombucha. During fermentation, the pH level of CK-MOX was gradually reduced, and total acidity slightly increased. Antioxidant activity, measured by DPPH, ABTS, and oxygen radical absorbance capacity assays, markedly increased after fermentation. Moreover, fermented CK-MOX (Day15) exhibited anti-proliferative and anti-migratory activities against EJ human bladder carcinoma cells. Western immunoblot assays showed that treatment with CK-MOX significantly up-regulated phospho-extracellular signaling kinase (ERK) levels. To distinguish whether or not up-regulation of phospho-ERK is the cause or effect, we investigated the viability of EJ cells in the presence of U0126, a mitogen activated protein kinase/ERK kinase 1/2 inhibitor. Pre-treatment with U0126 rescued cells from CK-MOX-induced cell death, which indicates phospho-ERK may be a key regulator in the mechanism of CK-MOX-induced apoptosis of EJ bladder cancer cells. In conclusion, CK-MOX, fermented by a defined composition of bacterial starters, shows antioxidant capacity and anti-cancer activity against EJ bladder cancer cells.

• Journal of Korean Medicine Rehabilitation
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• v.19 no.2
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• pp.103-112
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• 2009

Objectives : This study was to evaluate the pharmacological effect of Korea Red Ginseng aqueous extract (KRGE) on serum-deprived apoptosis of neuronal-like pheochromocytoma PC12 cells and to investigate its underlying action mechanism. Methods : KRGE was prepared by extracting Korea Red Ginseng with hot water and concentrating using a vacuum evaporator. Cell viability was determined after incubation of cells with KRGE or chemical inhibitor in serum-deprived medium for 60 h by counting intact nuclei following lysing of the cell membrane. Caspase activities were measured using chromogenic substrates and signal-associated protein phosphorylation and cytochrome c release were determined by Western blot analyses using their specific antibodies. Results : Serum deprivation induced PC12 cell death, which was accompanied by typical morphological features of apoptotic cell, such as nuclear fragmentation, caspase-3 activation, and cytochrome c release. This apoptotic cell death was significantly inhibited by KRGE and caspase-3 inhibitor, but not by the addition of NMA, ODQ, and PD98059. KRGE promoted phosphorylation of Akt and Bad, and this phosphorylation was inhibited by the PI3K inhibitor LY92004. In addition, this inhibitor also reversed KRGE-mediated protection of PC 12 cells from serum deprivation. These results suggested that KRGE protects PC12 cells from serum deprivation-induced apoptosis through the activation of PI3K/Akt-dependent Bad phosphorylation and cytochrome c release, resulting in caspase-3 activation. Conclusions : KRGE should be considered as a potential therapeutic drug for brain diseases including stroke induced by apoptosis of neuronal cells.

• The Journal of Korean Medicine
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• v.20 no.1 s.37
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• pp.142-150
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• 1999

In order to elucidate toxic the mechanism of myocardial damage and the protective effect of herbal extract, Sophorae Radix(SR) against myocardiotoxicity, the cytotoxic effect of adriamycin and cardioprotective effect of SR were examined by MTT assay, LDH activity, heart beat rate and light microscopy after cultured myocardial cells derived from neonatal mouse were treated with various concentrations of adriamycin, an inducer of myocardiotoxicity. Adriamycin induced a decrease of cell viability, an increase in the amount of lactate dehydrogenase(LDH), and a decrease in the heart beat rate and a decrease in the number of cells, when administered to cultures myocardial cells in a dose-dependent manner. In cardioprotective effect of SR. SR showed the decrease of amount of LDH, and an increase of heart beating rate and cells in number on cultured myocardial cells damaged by adriamycin. From the above results, it is suggested that adriamycin shows toxic effect in cultured myocardial cells derived from a neonatal mouse, and herbal extract such as SR is very effective in the prevention of adriamycin-induced cardiotoxicity.

• The Korea Journal of Herbology
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• v.26 no.3
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• pp.47-56
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• 2011

Objectives : This study investigated whether the water extract of Spatholobi Caulis (SCE) has the ability to protect hepatocyte against oxidative stress induced by tert-butylhydroperoxide (tBHP) in vitro and $CCl_4$ in vivo. Methods : In vitro, HepG2 cells pre-treated with Spatholobi Caulis water extract (1, 3, 10, $30{\mu}g$/ml) for 12h and further incubated with tBHP ($100{\mu}M$) for the next 12h. Cell viability was assessed by MTT assay. In vivo, rats were orally administrated with the aqueous extract of Spatholobi Caulis (SCE; 50, 100 mg/kg) for 4 days and then, injected with $CCl_4$ 1 mg/kg body weight to induce acute liver damage. Results : Treatment with SCE inhibited cell death induced by tBHP, as evidenced by alterations in the levels of the proteins associated with apoptosis:SCE prevented a decrease in $Bcl_2$, and cleavage of poly(ADP-ribose)polymerase and pro-caspase-3. Moreover, SCE inhibited the ability of tBHP to generate $H_2O_2$ production, thereby restoring GSH content. Moreover, SCE treatments in rats effectively decreased liver injuries induced by a single dose of $CCl_4$, as evidenced by decreases in hepatic degeneration and inflammation as well as plasma alanine aminotransferase and lactate dehydrogenase activities. Consistently, treatments of SCE also protected liver in rats stimulated by $CCl_4$, as indicated by restoration GSH and prevention of MDA in the liver. Conclusions : SCE has the ability 1) to protect hepatocyte against oxidative stress induced by tBHP and 2) to prevent $CCl_4$-inducible acute liver toxicity. Present findings may be informative not only in elucidating the pharmacological mechanism of Spatholobi Caulis, but in determining its potential application for oxidative cellular damage in the liver.

• Polymer(Korea)
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• v.31 no.5
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• pp.454-459
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• 2007

Gene therapy using low molecular weight water soluble chitosan (LMWSC) as polycationic polymer shows good biocompatibility, but low transfection efficiency. The mechanism of folic acid (FA) uptake in the cells to promote targeting and internalization could improve transfection rates. The objective of this study was to synthesize and characterize the WSCFA-DNA complex and evaluate their cytotoxicity, in vitro. In $^1H-NMR$ spectra, specific peaks appeared both of FA and LMWSC in $D_2O$. WSCFA nanoparticles have spherical shapes with particle size show below 110 nm. In the cell cytotoxicity test, the WSCFA-DNA complex showed high cell viability, in vitro. Gel electrophoresis showed condensed DNA within the carriers. hi vitro transfection efficiency was assayed by fluorescence spectroscopy WSCFA nanoparticles have less cytotoxicity, good DNA condensation and particle size around 110 nm, which makes them a promising candidate as a non-viral gene vector.