• Journal of Oriental Neuropsychiatry
• /
• v.20 no.2
• /
• pp.121-131
• /
• 2009

Objectives : From Scrophularia buergeriana water extract(SBW), has been used in vivo test for its beneficial effects on neuronal survival and neuroprotective functions, particularly in connection with APP-related dementias and Alzheimer's disease(AD). $A{\beta}$ oligomer derived from proteolytic processing of the ${\beta}$-amyloid precursor protein(APP), including the amyloid-${\beta}$ peptide($A{\beta}$), play a critical role in the pathogenesis of Alzheimer's dementia. Methods : Using drosophila APP model on APP-induced neuronal cytotoxicity, we demonstrated that SBW prevents neurotoxicity of $A{\beta}$ oligomer, which are the behavior, and possibly causative, feature of AD. We investigated the neuroprotective effects of SBW against the effects of oligomeric $A{\beta}$ and fly behaveior and life span by UAS-GRIM/APP-GAL within transgenic flies. Results and Conclusions : SBW repaired damage leading to the behaveior of APP-induced fly and delayed life span. These results suggest that neuronal damage in AD might be due to two factors: a direct $A{\beta}$ oligomer toxicity and multiple cellular and molecular neuroprotective mechanisms, including attenuation of apoptosis and direct inhibition of $A{\beta}$ oligomer, underlie the neuroprotective effects of SBW.

• Toxicological Research
• /
• v.23 no.3
• /
• pp.263-269
• /
• 2007

Although taurine (2-aminoethanesulfonic acid) can inhibit oxidative stress in both animal and epidemiological studies, it is obscure whether taurine directly scavenges oxy-radicals or indirectly regulates oxidant production and/or antioxidant defense system. The reason for this discrepancy remains unknown but may be due, in part, to the lack of a validated assay system for evaluating oxy-radical scavenging capacity. The antioxidant activities of taurine and hypotaurine (2-aminoethanesulfinic acid), a precursor of taurine, against peroxyl radicals, hydroxyl radicals and peroxynitrites were determined by the total oxy-radical scavenging capacity (TOSC) assay and cell-based assay using H4IIE cells. tert-Butylhydroperoxide or hydrogen peroxide-induced cell toxicity determined by MTT assay was markedly inhibited by 10mM taurine or hypotaurine. The tert-butylhydroperoxide- or hydrogen peroxide-induced changes in oxidative stress markers, such as cellular glutathione and malondialdehyde, were ameliorated by 10mM taurine or hypotaurine. However, specific TOSC values calculated from the slope of the linear regression for taurine against peroxyl radicals, hydroxyl radicals or peroxynitrites were all less than 1 TOSC/mM. On the other hand specific TOSC values for hypotaurine against peroxyl radicals, hydroxyl radicals or peroxynitrites were 48, 2096, or 69 TOSC/mM, respectively. These results suggest that taurine protects cells against oxidative insults, which is not ascribed to directly scavenging activity of taurine against oxy-radicals. These results support the idea that the oxidation state of sulfur in antioxidants may be a determinant of oxy-radical scavenging capacity.

• Biomolecules & Therapeutics
• /
• v.28 no.4
• /
• pp.311-319
• /
• 2020

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a newly emerging viral disease with fatal outcomes. However, no MERS-CoV-specific treatment is commercially available. Given the absence of previous structure-based drug discovery studies targeting MERS-CoV fusion proteins, this set of compounds is considered the first generation of MERS-CoV small molecule fusion inhibitors. After a virtual screening campaign of 1.56 million compounds followed by cell-cell fusion assay and MERS-CoV plaques inhibition assay, three new compounds were identified. Compound numbers 22, 73, and 74 showed IC₅₀ values of 12.6, 21.8, and 11.12 µM, respectively, and were most effective at the onset of spike-receptor interactions. The compounds exhibited safe profiles against Human embryonic kidney cells 293 at a concentration of 20 µM with no observed toxicity in Vero cells at 10 µM. The experimental results are accompanied with predicted favorable pharmacokinetic descriptors and drug-likeness parameters. In conclusion, this study provides the first generation of MERS-CoV fusion inhibitors with potencies in the low micromolar range.

• The Plant Pathology Journal
• /
• v.32 no.1
• /
• pp.8-15
• /
• 2016

To identify a novel biopesticide controlling rice blast disease caused by Magnaporthe oryzae, 700 plant extracts were evaluated for their inhibitory effects on mycelial growth of M. oryzae. The L. foenum-graecum Herba extract showed the lowest inhibition concentration ($IC_{50}$) of $39.28{\mu}g/ml$, which is lower than the $IC_{50}$ of blasticidin S ($63.06{\mu}g/ml$), a conventional fungicide for rice blast disease. When treatments were combined, the $IC_{50}$ of blasticidin S was dramatically reduced to $10.67{\mu}g/ml$. Since ABC transporter genes are involved in fungicide resistance of many organisms, we performed RT-PCR to investigate the transcriptional changes of 40 ABC transporter family genes of M. oryzae treated with the plant extract, blasticidin S, and tetrandrine, a recognized ABC transporter inhibitor. Four ABC transporter genes were prominently activated by blasticidin S treatment, but were suppressed by combinational treatment of blasticidin S with the plant extract, or with tetrandrine that didn't show cellular toxicity by itself in this study. Mycelial death was detected via confocal microscopy at 24 h after plant extract treatment. Finally, subsequent rice field study revealed that the plant extract had high control efficacy of 63.3% and should be considered a biopesticide for rice blast disease. These results showed that extract of L. foenum graecum Herba suppresses M. oryzae ABC transporter genes inducing mycelial death and therefore may be a potent novel biopesticide.

• Molecular & Cellular Toxicology
• /
• v.2 no.3
• /
• pp.202-211
• /
• 2006

Our objective is to identify molecular factors which contribute to the increased risk of smoke in human. About 677 workers who had control and experimental groups according to their urinary Naphthol levels were enrolled in our study. In the present study, we investigated the effects of smoking on gene expression profiles in human. We determined differential gene expression patterns in smoker versus non-smoker using cDNA microarray. Specific genes were up-or down-regulated according to smoking and age. Inflammatory related genes such as cytokine, interleukin, and tumor necrosis factor were up-regulated, DNA repair related genes such as high-mobility group (nonhistone chromosomal) protein 1, and protein 2 were down-regulated, apoptosis related genes such as myeloperoxidase and Bcl-2-associated athanogene were down-regulated, and cell cycle related genes were down-regulated. In our epidemiological study, notably, inflammatory, DNA repair, apoptosis, signal transduction, metabolism, cell cycle, cell proliferation, transcription related genes were regulated.

• Molecular & Cellular Toxicology
• /
• v.1 no.4
• /
• pp.268-274
• /
• 2005

Bromobenzene (BB) is well known hepatotoxicant. Also, BB is an industrial solvent that arouses toxicity predominantly in the liver where it causes centrilobular necrosis. BB is subjected to Cytochrome P450 mediated epoxidation followed by either conjugation with glutathione, enzymatic hydrolysis or further oxidation. In this study, we focused on BB-induced gene expression at non-hepatotoxic dose. Mice were exposed to two levels of BB, sampled at 24 h, and hepatic gene expression levels were determined to evaluate dose dependent changes. When examining the toxic dose of BB treated group in other previous studies, genes related to heat shock protein, oxidative stress, and drug metabolism are expressed. Compared to these results, our study, in which non-toxic dose of BB was administrated, showed similar patterns as the toxic conditions above. The purpose of the study was to select genes that showed changes in relation to the differing dose through confirmation of the difference within transcriptomic boundaries, but those that are not detected by the existing classic toxicology tools in non-hepatotoxic dose.

• Molecular & Cellular Toxicology
• /
• v.1 no.4
• /
• pp.275-280
• /
• 2005

Carbon tetrachloride ($CCl_4$) is well known hepatotoxicant. Its overdose cause severe centrilobular hepatic necrosis in human and experimental animals. We administered $CCl_{4}$ at low (0.2 mL/kg p.o.) and high (2 mL/kg p.o.) doses to mice. Mice were sacrificed at 24 h after administration. We evaluated liver toxicity by serum AST and ALT level and by microscopic observation. Using cDNA chip, we conducted gene expression analysis in liver. Mean serum activities of the hepatocellular leakage enzymes, ALT and AST, were significantly increased compare to control, respectively, in the low and high dose groups. H&E evaluation of stained liver sections revealed $CCl_{4}-related$ histopathological findings in mice. Moderate centrilobular hepatocellular necrosis was present in all $CCl_{4}$ treated mice. We found that gene expression pattern was very similar between low and high dose group. However, some stress related genes were differently expressed. These results could be a molecular signature for the degree of liver injury. Our data suggest that the degree of severity could be figure out by gene expression profiling.

• Molecular & Cellular Toxicology
• /
• v.4 no.4
• /
• pp.360-365
• /
• 2008

In the last several years, studies on the association of oxidative stress damage with exposure in the work place have been conducted. Xenobiotics create an imbalance of the homeostasis between oxidant molecules and antioxidant defense. By monitoring oxidative stress biomarkers, information was obtained on damages induced by oxidative stress and the toxicity of xenobiotics. In the present study, a Job Exposure Matrix (JEM) was constructed using the data from the Working Environment Measurement (WEM) of painters in the shipyard industry from the past 3 years to assess the exposure status. Additionally, by measuring the concentration of urinary malondialdehyde (MDA), the effect of lipid peroxidation was examined. The subjects consisted of 68 workers who were exposed to mixed organic solvents in the painting process and 25 non-exposure controls. The exposure indices of the exposure groups were significantly different (sprayer: 0.83, touchup: 0.54, assistant: 0.13, P<0.05). The urinary MDA concentration of the exposure group was 48.60${\pm}$ 39.23 ${\mu}mol$/mol creatinine, which was significantly higher than 18.03${\pm}$16.33 ${\mu}mol$/mol creatinine of the control group (P<0.05). From the multiple regression analysis of urinary MDA, the regression coefficient for exposure grade was statistically significant. In future studies, evaluation of the antioxidant levels of subjects should be performed simultaneously with quantitative exposure measurements.

• Korean Journal of Clinical Laboratory Science
• /
• v.36 no.1
• /
• pp.55-63
• /
• 2004

The hepatotherapeutic effect of the extract of Lycii fructus has been studied in rats against $CCl_4$ induced liver toxicity. The rats were orally treated with $CCl_4$ (corn oil/$CCl_4$ 1:1, $1m{\ell}/kg$) and then $CCl_4$ ($0.5m{\ell}/kg$) administered four times for 2 weeks. The extracts of L. fructus have been administered every day for 2 weeks after the last $CCl_4$ injection. The experimental groups consisted of negative control (G1), positive control ($CCl_4$ alone; G2), extract of L. fructus (50 mg/kg; G3, 100 mg/kg; G4, 200 mg/kg; G5), respectively. There was a significant decrement to G2 on the serum level of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase in G5. Also, the content of thiobarbituric acid reactive substance, and phosphatidylcholine hydroperxidase, a marker of lipid peroxidation, in the liver were decreased significantly G5 and G4 compared with G2. Although, catalase or superoxide dismutase, antioxidant enzyme, in the liver were decreased significantly too, it would not be a good sign for the liver. In histopathological findings, such a hepatocellular vacuolar degeneration, lobular restructure, cellular infiltration, necrosis, and so on were shown severely in G2. However, G4 and G5 was shown a mild cytoplasmic vacuolation and inflammatory cell. In conclusion, as a protection against cell damage, lipid peroxidation and serum level, it suggested that the extract of Lycii fructus would have been a therapeutic effect of liver injury directly.

• KSBB Journal
• /
• v.29 no.1
• /
• pp.36-41
• /
• 2014

Skin disease is one of the most common diseases and its incidence is increasing dramatically in modern society. Specially, many attempts have been made to treat chronic skin inflammation diseases, such as psoriasis and atopic dermatitis, but effective therapies for the immune cell-mediated skin diseases, including psoriasis and atopic dermatitis have not been developed. Until recently, several drug candidates which were claimed to be effective for skin diseases have been reported, but most of them are not used to treat chronic skin disease. Especially, Psoriasis is characterized by excessive growth and aberrant differentiation of keratinocytes, but is fully reversible with appropriate therapy. The trigger of the keratinocyte response is thought to be activation of the cellular immune system, with T cells and various immune-related cytokines. Formation of new blood vessels starts with early psoriatic changes and disappears with disease clearance. Several angiogenic mediators are up-regulated in psoriasis development. Contact- and mediator-dependent factors derived from keratinocytes, mast cells and immune cells may contribute to the strong blood vessel formation of psoriasis. New technologies and experimental models provide new insights into the role of angiogenesis in psoriasis pathogenesis. TMP and its derivatives themselves effectively inhibited in vitro cell migration, tube formation, and the expression of angiogenic factors. However, TMP and its derivatives induced side effects including hemolysis and local side effects. Therefore, in an attempt to reduce the toxicity and the undesirable side effects of TMP and derivatives, a liposomal formulation was prepared and tested for its effectiveness. TMP and derivatives liposomes retained the effectiveness of TMP in vitro while side effects were reduced. These results support the conclusion that TMP effectively inhibits in vitro angiogenesis, with the possibility that use as a psoriasis relief agent.