• Proceedings of the PSK Conference
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• 2003.04a
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• pp.178.2-178.2
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• 2003

To develope the novel anti-allergic drug, many sophoricoside derivatives were synthesized. Among these derivatives, JSH-II-3, JSH-Ⅵ-3, JSH-Ⅶ-3, and JSH-Ⅷ-3 were selected and subjected to high throughput toxicity screening (HTTS) because they revealed strong IL-5 inhibitory activity and limitation of Quantity. Mouse lymphoma thymidine kinase ($tk^{+/-}$) gene assay(MOLY) and single cell gel electrophoresis (Comet) assay in mammalian cells were used as HTTS tool in our laboratory. (omitted)

• Journal of Korean Academy of Oral and Maxillofacial Radiology
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• v.27 no.1
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• pp.43-53
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• 1997

The purpose of this study was to aid in the prediction of tumor cell tolerance to radiotherapy and/or chemotherapy. For this study, cell surviving curves were obtained for mouse lymphoma YAC-1 cell line using semi automated MTT assay. 2, 4,6, 8, 10Gy were irradiated at a dose rate of 210cGy/rnin using /sup 60/Co Irradiator ALDORADO 8. After irradiation, YAC-1 cell lines(3×10⁴cells/ml) were exposed to bleomycin or cisplatin for 1 hour. The viable cells were determined for each radiation dose and/or each concentration of drug at the 4th day. And they were compared to control values. The obtained results were as follows : 1. The surviving curve with gentle slope was obtained after irradiation of 2, 4, 6, 8, 10 Gy on YAC-1 cell line. 2. The cytotoxicity of bleomycin or cisplatin was increased significantly at all concentration of 0.2㎍/ml, 2㎍/ml and 20㎍/ml on YAC-1 cell line (P<0.01). And the cytotoxicity of cisplatin was greater than that of bleomycin at all concentration on YAC-1 cell line (P<0.01). 3. There were no significant differences of surviving fractions among 4Gy, 6Gy and 8Gy after irradiation of each radiation dose with 2㎍/ml of bleomycin compared with irradiation only on YAC-1 cell line. 4. There was significant difference of surviving fraction between 2Gy and 10Gy after irradiation of each radiation dose with 2㎍/ml of cisplatin compared with irradiation only on YAC-1 cell line(P<0.05). 5. There were significant differences of surviving fractions between the groups of irradiation only and the groups of irradiation with 2㎍/ml of bleomycin or cisplatin at all doses of 2, 4, 6, 8 and 10Gy on YAC-1 cell line(P<0.05).

• Bulletin of the Korean Chemical Society
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• v.18 no.7
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• pp.711-714
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• 1997

In an effort to enhance the lipophilicities, thereby, the penetration into the cell membrane and to increase the antitumor activities of modified derivatives of 2',3'-didehydro-3'-deoxythymidine (d4T, 1), derivatives of 1 were designed and synthesized. Starting from thymidine, 1, 2',3'-didehydro-3'-deoxythymidine-5'-phosphate, disodium salt (d4T-p, 7), and two nicotinate esters of 1; 2',3'-didehydro-3'-deoxy-5'-O-(3-pyridinylcarbonyl)thymidine (d4T-NA, 5) and 2',3'-didehydro-3'-deoxy-5'-phosphoryl-O-(3-pyridinylcarbonyl)thymidine (d4T-p-NA, 8) were synthesized. The lipophilicities of the synthesized compounds were measured by P-values and antitumor activities of those were estimated against mouse leukemia P388, murine mammary carcinoma FM3A, and human histiocytic lymphoma U937 tumor cells in vitro. Although the lipophilicities of the nicotinate esters, 5 and 8 were increased 2.75- and 9.71-fold relative to that of 1 and 7, respectively, the synthesized compounds, 1, 5, 7, and 8 were found to be inactive against P388 and FM3A cells except weak antitumor activity against U937 cell.

• Advances in Traditional Medicine
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• v.3 no.2
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• pp.100-105
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• 2003

Systematic analysis of caffeine from the commercial samples of Indian tea leaves was performed by a routine method and the content of caffeine was found to be 19.0-37.4 mg/100 g leaves. The caffeine contents from coffee seeds and chicory from Indian origin were analyzed and found to be 0.6540-1.4920 g/100 g seeds. Caffeine contents of roasted Indian chicory roots were lower than either those of Indian tea leaves or Indian coffee seeds. The multidrug resistance (MDR) reversing effects were tested on a mouse leukemia cell line of L-5178 cells by methanol extracts [M1-M15] of Indian tea leaves and coffee seeds, comparing to a control of $({\pm})-verapamil$. The effects were measured by fluorescence ratio between treated and untreated group cells. Among fifteen methanol extracts, a Gemini tea [M6] (fluorescence activity ratio 5.26) had the most potent effect for L-5178 cells. The extract M6 was 0.63-fold of $({\pm})-verapamil$. We suggest that one of mechanisms of reversal by M6 might have strong affinity to dopamine $D_1$ and D_2$ receptors. Further studies with many more tumor and normal cell lines are necessary to confirm the MDR reversal specificity of coffee methanol extracts.

• Archives of Pharmacal Research
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• v.19 no.3
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• pp.235-239
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• 1996

Six, heretofore undescribed, $5^I-Methyl-5^I-(5-Substituted uracil-1-ylmethyl)-2^I-oxo-3^I-methylenetetrahydrofurans(F, Cl, Br, l, CH_3, H)(6a-f)$were synthesized and evaluated against three cell lines (FM-3A, P-388 and U-937). For the preparation of .alpha.-methylene-.gamma.-butyrolactone bearing 5-substituted uracils (6a-f), the effcient Reformatsky type reaction was employed which involves the treatment of ethyl .alpha.(bromomethyl) acrylate and zinc with the respective 5-substituted uracil-1-ylacetones (5a-f). The acetone derivatives (5a-f) were directly obtained by the respective alkylation reaction of 5-substituted uracils with chloroacetone in the presence of $K_{2}$$CO_{3}$(or NaH). These lactone compounds 6a-f exhibited moderate to significant activity in all of the three cell lines, and 6b, 6c and 6e showed significant antitumor activities (inhibitory concentrations ($IC_{50}$) ranged from 1.3-3.8 .mu.g/ml.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 2003.05a
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• pp.183-184
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• 2003

Sophoricoside was isolated as the inhibitor of IL-5 bioactivity from Sophora japonica (Leguminosae). It has been reported to have an anti-inflammatory effect on rat paw edema model. To develop as an anti-allergic drug, genotoxicity of sophoricoside was investigated in bacterial and mammalian cell system such as Ames bacterial test, chromosomal aberration assay, Comet assay and MOLY assay. In Ames test, sophoricoside of 5000 ∼ 313 $\mu\textrm{g}$/plate concentrations was not shown significant mutagenic effect in Salmonella typhimurium TA98, TA100, TA1535 and TA1537 strains. The cytotoxicity (IC$\_$50/ and IC$\_$20/) of sophoricoside was determined above the concentration of 5000 $\mu\textrm{g}$/ml in Chinese hamster lung (CHL) fibroblast cell and L5178Y mouse lymphoma cell line. At concentrations of 5000, 2500 and 1250 $\mu\textrm{g}$/ml, this compound was not induced chromosomal aberration in CHL fibroblast cell in the absence and presence of S-9 metabolic activation system. Also in comet assay, DNA damage was not observed in L5178Y cell line. Also in MOLY assay, sophoricoside of 5000 ∼ 313 $\mu\textrm{g}$/ml concentrations was not shown significant mutagenic effect in absence of S-9 metabolic activation system. However, the higher concentration of 5000 and 2500 $\mu\textrm{g}$/ml of sophoricoside induced the increased mutation frequency (MF) in the presence of S-9 metabolic activation system. From these results, no genotoxic effects of sophoricoside observed in bacterial systems whereas, genotoxic effects observed in mammalian cell systems in the presence of metabolic activation system. These results suggested that the metabolite(s) of sophoricoside can cause some genotoxic effects in mammalian cells.

• Biomolecules & Therapeutics
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• v.27 no.2
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• pp.178-184
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• 2019

Parkinson's disease is a neurodegenerative disease characterized by the progressive loss of dopaminergic neurons within the substantia nigra pars compacta. In the present study, we investigated whether ${\beta}-Lapachone$ (${\beta}-LAP$), a natural naphthoquinone compound isolated from the lapacho tree (Tabebuia avellanedae), elicits neuroprotective effects in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease mouse model. ${\beta}-LAP$ reduced the tyrosine hydroxylase (TH)-immunoreactive fiber loss induced by MPTP in the dorsolateral striatum, and alleviated motor dysfunction as determined by the rotarod test. In addition, ${\beta}-LAP$ protected against MPTP-induced loss of TH positive neurons, and upregulated B-cell lymphoma 2 protein (Bcl-2) expression in the substantia nigra. Based on previous reports on the neuroprotective role of nuclear factor-E2-related factor-2 (Nrf2) in neurodegenerative diseases, we investigated whether ${\beta}-LAP$ induces upregulation of the Nrf2-hemeoxygenae-1 (HO-1) signaling pathway molecules in MPTP-injected mouse brains. Western blot and immunohistochemical analyses indicated that ${\beta}-LAP$ increased HO-1 expression in glial fibrillary acidic protein-positive astrocytes. Moreover, ${\beta}-LAP$ increased the nuclear translocation and DNA binding activity of Nrf2, and the phosphorylation of upstream adenosine monophosphate-activated protein kinase (AMPK). ${\beta}-LAP$ also increased the localization of p-AMPK and Nrf2 in astrocytes. Collectively, our data suggest that ${\beta}-LAP$ exerts neuroprotective effect in MPTP-injected mice by upregulating the p-AMPK/Nrf2/HO-1 signaling pathways in astrocytes.

• Molecular & Cellular Toxicology
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• v.1 no.2
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• pp.99-105
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• 2005

Perchloroethylene (tetrachloroethylene, PCE), a dry cleaning and degreasing solvent, can enter ground-water through accidental leak or spills. PCE can be degraded to trichloroethylene (TCE), 1, 1-dichloroethylene (DCE) and vinyl chloride (VC) as potential bio-product. These compounds have been reported that they can cause clinical diseases and cytotoxicity. However, only a little genotoxic information of these compounds has been known. In this study, we investigated DNA single strand breaks of PCE, TCE, DCE and VC by single cell gel electrophoresis assay, (comet assay) which is a sensitive, reliable and rapid method for DNA single strand breaks with mouse lymphoma L5178Y cells. From these results, $37.5\;{\mu}g/ml$ of PCE, $189\;{\mu}g/ml$ of TCE and $56.4\;{\mu}g/ml$ of DCE were revealed significant DNA damages in the absence of S-9 metabolic activation system meaning direct-acting mutagen. And in the presence of S-9 metabolic activation system, $41.5\;{\mu}g/ml$ of PCE, $328.7\;{\mu}g/ml$ of TCE and $949\;{\mu}g/ml$ of DCE were induced significant DNA damage. In the case of VC, it was revealed a significant DNA damage in the presence of S-9 metabolic activation system. Therefore, we suggest that chloroethylene compounds (PCE, TCE, DCE and VC) may be induced the DNA damage in a mammalian cell.

• Journal of Ginseng Research
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• v.41 no.3
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• pp.386-391
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• 2017

Background: Korean Red Ginseng (KRG) is an ethnopharmacological plant that is traditionally used to improve the body's immune functions and ameliorate the symptoms of various diseases. However, the antitumorigenic effects of KRG and its underlying molecular and cellular mechanisms are not fully understood in terms of its individual components. In this study, in vitro and in vivo antitumorigenic activities of KRG were explored in water extract (WE), saponin fraction (SF), and nonsaponin fraction (NSF). Methods: In vitro antitumorigenic activities of WE, SF, and NSF of KRG were investigated in the C6 glioma cell line using cytotoxicity, migration, and proliferation assays. The underlying molecular mechanisms of KRG fractions were determined by examining the signaling cascades of apoptotic cell death by semiquantitative reverse transcriptase polymerase chain reaction and Western blot analysis. The in vivo antitumorigenic activities of WE, SF, and NSF were investigated in a xenograft mouse model. Results: SF induced apoptotic death of C6 glioma cells and suppressed migration and proliferation of C6 glioma cells, whereas WE and NSF neither induced apoptosis nor suppressed migration of C6 glioma cells. SF downregulated the expression of the anti-apoptotic gene B-cell lymphoma-2 (Bcl-2) and upregulated the expression of the pro-apoptotic gene Bcl-2-associated X protein (BAX) in C6 glioma cells but had no effect on the expression of the p53 tumor-suppressor gene. Moreover, SF treatment resulted in activation of caspase-3 as evidenced by increased levels of cleaved caspase-3. Finally, WE, SF, and NSF exhibited in vivo antitumorigenic activities in the xenograft mouse model by suppressing the growth of grafted CT-26 carcinoma cells without decreasing the animal body weight. Conclusion: These results suggest that WE, SF, and NSF of KRG are able to suppress tumor growth via different molecular and cellular mechanisms, including induction of apoptosis and activation of immune cells.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.9
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• pp.1256-1263
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• 2015

Citrus junos Sieb. ex Tanaka has been traditionally called Yuza in Korea and is used as a cuisine material or tea as well as medicinal herb. In this study, we evaluated the immune-enhancing effect of Citrus junos ethanol extract (CJE) on RAW264.7 mouse macrophage and primary immunocytes. CJE treatment showed increased macrophage activity in a dose-dependant manner. CJE also enhanced natural killer (NK) cell activity. We measured lactate dehydrogenase (LDH) level as a measurement of NK cell cytotoxicity against YAC-1 lymphoma cells. CJE treatment showed an increased LDH level in a dose-dependent manner. Finally, we evaluated the effect of CJE on mouse primary splenocyte proliferation. CJE treatment slightly increased splenocyte proliferation compared to the control. The results of this study suggest that CJE can help immune function via macrophage cytokine production, increased NK cell activity, and splenocyte proliferation.