• Bulletin of the Korean Chemical Society
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• v.24 no.1
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• pp.65-69
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• 2003

The kinetic and chemical mechanisms of AChE-catalyzed hydrolysis of short-chain thiocholine esters are relatively well documented. Up to propanoylthiocholine (PrTCh) the chemical mechanism is general acid-base catalysis by the active site catalytic triad. The chemical mechanism for the enzyme-catalyzed butyrylthiocholine(BuTCh) hydrolysis shifts to a parallel mechanism in which general base catalysis by E199 of direct water attack to the carbonyl carbon of the substrate. [Selwood, T., et al. J. Am. Chem. Soc. 1993, 115, 10477- 10482] The long chain thiocholine esters such as hexanoylthiocholine (HexTCh), heptanoylthiocholine (HepTCh), and octanoylthiocholine (OcTCh) are hydrolyzed by electric eel acetylcholinesterase (AChE). The kinetic parameters are determined to show that these compounds have a lower Michaelis constant than BuTCh and the pH-rate profile showed that the mechanism is similar to that of BuTCh hydrolysis. The solvent isotope effect and proton inventory of AChE-catalyzed hydrolysis of HexTCh showed that one proton transfer is involved in the transition state of the acylation stage. The relationship between the dipole moment and the Michaelis constant of the long chain thiocholine esters showed that the dipole moment is the most important factor for the binding of a substrate to the enzyme active site.

• Preventive Nutrition and Food Science
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• v.11 no.3
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• pp.191-197
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• 2006

Matrix metalloproteinase-2 (MMP-2) is a key enzyme involved in tumor invasiveness. The plant of Magnolia officinalis Rehd. et Wils. is often included as an ingredient in various herbal remedies recommended for cancer theraphies in Korea. Various extracts prepared from stems of M. officinalis were tested for cytotoxic activity on human hepatocellular carcinoma cell line, SK-Hep cells using the XTT assay method. Then, the inhibitory effect was examined on MMP-2 activity using gelatin zymography. Methanol (MeOH) extract of M. officinalis caused the strongest inhibition of the MMP-2 activity, as measured by gelatin zymography method for enzyme activity. $IC_{50}$ values of fractions on MMP-2 activity were in a range of $4.9{\sim}11.3\;{\mu}g/mL$. Among each fraction, butanol and ethylacetate (EtOAc) fractions showed the strong inhibitory activities ($IC_{50}=10.7\;and\;4.9\;{\mu}g/mL$, respectively). When the M. officinalis's constituents such as magnolol, honokiol, (-)-epigallocatechin gallate (EGCG) and ovovatol were examined for inhibitory effects on MMP-2 activity, EGCG showed strong inhibitory activity. However, MeOH extract of M. officinalis was dose-dependently inhibited to MMP-2 activity. The MeOH extract, hexane and EtOAc fractions $(IC_{50}\;of\;>200\;{\mu}g/mL)$ exhibited weak cytotoxicity activity, while butanol $(IC_{50}=80\;{\mu}g/mL)$ and chloroform fractions $(IC_{50}=90\;{\mu}g/mL)$ exhibited relatively strong cytotoxic activity. From these results, M. officinalis could be suitable for cancer treatment and chemopreventive drugs.

• Bulletin of the Korean Chemical Society
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• v.34 no.5
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• pp.1407-1413
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• 2013

A new compound, perforaphenonoside A (1), along with 11 known compounds (2-12) were isolated from a methanol extract of adventitious roots of Hypericum perforatum. Their chemical structures were elucidated using chemical and physical methods as well as comparison of NMR and mass spectral data with previously reported data. Their inhibition of NF-${\kappa}B$ and activation of PPAR was measured in HepG2 cells using a luciferase reporter system. Among the compounds 3, 6, 7 and 12 inhibited NF-${\kappa}B$ activation stimulated by TNF${\alpha}$ in a dose-dependent manner, with $IC_{50}$ values ranging from 0.85 to $8.10{\mu}M$. Moreover, compounds 1-3, 7, 11 and 12 activated the transcriptional activity of PPARs in a dose-dependent manner, with $EC_{50}$ values ranging from 7.3 to $58.7{\mu}M$. The transactivational effects of compounds 1-3, 7, 11 and 12 were evaluated on three individual PPAR subtypes. Among them, compound 2 activated $PPAR{\alpha}$ transcriptional activity, with 153.97% stimulation at $10{\mu}M$, while compounds 1, 2 and 11 exhibited transcriptional activity of $PPAR{\gamma}$, with stimulation from 124.76% to 126.91% at $10{\mu}M$.

• Nuclear Engineering and Technology
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• v.45 no.2
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• pp.151-164
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• 2013

A key input for the assessment of Human Error Probabilities (HEPs) with Human Reliability Analysis (HRA) methods is the evaluation of the factors influencing the human performance (often referred to as Performance Shaping Factors, PSFs). In general, the definition of these factors and the supporting guidance are such that their evaluation involves significant subjectivity. This affects the repeatability of HRA results as well as the collection of HRA data for model construction and verification. In this context, the present paper considers the TAsk COMplexity (TACOM) measure, developed by one of the authors to quantify the complexity of procedure-guided tasks (by the operating crew of nuclear power plants in emergency situations), and evaluates its use to represent (objectively and quantitatively) task complexity issues relevant to HRA methods. In particular, TACOM scores are calculated for five Human Failure Events (HFEs) for which empirical evidence on the HEPs (albeit with large uncertainty) and influencing factors are available - from the International HRA Empirical Study. The empirical evaluation has shown promising results. The TACOM score increases as the empirical HEP of the selected HFEs increases. Except for one case, TACOM scores are well distinguished if related to different difficulty categories (e.g., "easy" vs. "somewhat difficult"), while values corresponding to tasks within the same category are very close. Despite some important limitations related to the small number of HFEs investigated and the large uncertainty in their HEPs, this paper presents one of few attempts to empirically study the effect of a performance shaping factor on the human error probability. This type of study is important to enhance the empirical basis of HRA methods, to make sure that 1) the definitions of the PSFs cover the influences important for HRA (i.e., influencing the error probability), and 2) the quantitative relationships among PSFs and error probability are adequately represented.

• Journal of Ginseng Research
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• v.44 no.2
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• pp.215-221
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• 2020

Background: Panax ginseng has been used for a variety of medical purposes in eastern countries for more than two thousand years. From the extensive experiences accumulated in its long medication use history and the substantial strong evidence in modern research studies, we know that ginseng has various pharmacological activities, such as antitumor, antidiabetic, antioxidant, and cardiovascular system-protective effects. The active chemical constituents of ginseng, ginsenosides, are rich in structural diversity and exhibit a wide range of biological activities. Methods: Ginsenoside constituents from P. ginseng flower buds were isolated and purified by various chromatographic methods, and their structures were identified by spectroscopic analysis and comparison with the reported data. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H- tetrazolium bromide method was used to test their cytotoxic effects on three human cancer cell lines. Results: Six ginsenosides, namely 6'-malonyl formyl ginsenoside F₁ (1), 3β-acetoxyl ginsenoside F₁ (2), ginsenoside Rh₂₄ (6), ginsenoside Rh₂₅ (7), 7β-hydroxyl ginsenoside Rd (8) and ginsenoside Rh₂₆ (10) were isolated and elucidated as new compounds, together with four known compounds (3-5 and 9). In addition, the cytotoxicity of these isolated compounds was shown as half inhibitory concentration values, a tentative structure-activity relationship was also discussed based on the results of our bioassay. Conclusion: The study of chemical constituents was useful for the quality control of P. ginseng flower buds. The study on antitumor activities showed that new Compound 1 exhibited moderate cytotoxic activities against HL-60, MGC80-3 and Hep-G2 with half inhibitory concentration values of 16.74, 29.51 and 20.48 μM, respectively.

• Journal of Ginseng Research
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• v.44 no.2
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• pp.267-273
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• 2020

Background: Continuous exposure to high temperatures can lead to heat stress. This stress response alters the expression of multiple genes and can contribute to the onset of various diseases. In particular, heat stress induces oxidative stress by increasing the production of reactive oxygen species. The liver is an essential organ that plays a variety of roles, such as detoxification and protein synthesis. Therefore, it is important to protect the liver from oxidative stress caused by heat stress. Korean ginseng has a variety of beneficial biological properties, and our previous studies showed that it provides an effective defense against heat stress. Methods: We investigated the ability of Korean Red Ginseng and Korean black ginseng extracts (JP5 and BG1) to protect against heat stress using a rat model. We then confirmed the active ingredients and mechanism of action using a cell-based model. Results: Heat stress significantly increased gene and protein expression of oxidative stress-related factors such as catalase and SOD2, but treatment with JP5 (Korean Red Ginseng extract) and BG1 (Korean black ginseng extract) abolished this response in both liver tissue and HepG2 cells. In addition, JP5 and BG1 inhibited the expression of inflammatory proteins such as p-NF-κB and tumor necrosis factor alpha-α. In particular, JP5 and BG1 decreased the expression of components of the NLRP3 inflammasome, a key inflammatory signaling factor. Thus, JP5 and BG1 inhibited both oxidative stress and inflammation. Conclusions: JP5 and BG1 protect against oxidative stress and inflammation induced by heat stress and help maintain liver function by preventing liver damage.

• Korean Journal of Food Science and Technology
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• v.38 no.2
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• pp.262-267
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• 2006

Inhibitory effects of fungal metabolites isolated from foodstuffs on growth of human cancer cell lines were evaluated. Isolated strains were divided into four classes based on color (aerial, reverse), shape, and growth speed. Fungal metabolites extracted with ethyl acetate were investigated for their growth inhibition on six kinds of human cancer cells by MTT assay. Ethyl acetate extract showed high growth inhibition against all cancer cells tested, with D4 exhibiting the strongest growth inhibition effects against Kato III, AGS, Hepa1c1c7, and MDA-MB-231 cancer cells. These results suggest ethyl acetate extract from fungal metabolites as effective natural cancer therapeutic material.

• Food Science and Biotechnology
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• v.16 no.1
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• pp.133-137
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• 2007

The Strain TFM-7, Which has an antitumor effect, was isolated from Kefir and identified based on analysis using the API 50 CHL kit and 265 rDNA sequencing. Strain TFM-7 was confirmed to belong to the genus Kluyveromyces. Analysis of the 265 rDNA nucleotide sequences found strain TFM-7 to be related to Kluyveromyces marxianus. NRRL Y-828IT. K. marxianus. TFM-7 was cultured with potato dektrose broth medium at $27^{\circ}C$ for 72 hr, and its inhibition effects on the proliferation of seven tumor cell lines and a normal cell line were assessed using the MTT assay. The antitumor effects and growth characteristics of K. marxianus TFM-7 were investigated during a culture period of 7 days. By the $3^{rd}\;day$, K. marxianus TFM-7 showed a dry cell weight 2.39 g/L, a pH of 4.39, an ethanol content of 0.89%, and an inhibition effect on the proliferation of seven tumor cell lines above 50%, except for A-549 tumor cell line. K. marxianus TFM-7 was the most effective at inhibiting the growth of Hep-2 cell line among all tumor cell lines tested. Growth inhibition of a normal cell line, NIH/3T3, was less than 35%, suggesting a decreased level of cytotoxicity toward normal cells. These results indicate that K. marxianus TFM-7 may have used as a yeast strain with antitumor activity.

• Journal of Life Science
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• v.17 no.10
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• pp.1381-1386
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• 2007

To elucidate the changes in physiological activities of Scutellariae baicalensis by heating, composition analysis with HPLC and evaluation of physiological activities of extracts were conducted. HPLC analysis of CW(water extract at room temperature) and CHW(heat treated CW) indicated that two distinctive peaks in the HPLC chromatogram were disappeared after boiling and additional peak was newly observed. This observation suggested that certain chemical changed in the extract occurred by heat treatment. In the estimation of physiological activities, CW showed higher ACE inhibiting activity than CHW. In the case of cytotoxic activity against cancer cells, CW exhibited higher activity than CHW against CCL-185. On the other hand, CHW showed higher activity than CW against HeLa, SNU-601 and HepG2. In addition, CHW showed the inhibitory effect on melanogenesis (80% inhibition) while CW did not show any activity.

• Preventive Nutrition and Food Science
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• v.15 no.4
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• pp.255-261
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• 2010

Ischemic stroke, a major cause of death and disability worldwide, is caused by occlusion of cerebral arteries that, coupled with or without reperfusion, results in prolonged ischemia (hypoxia and hypoglycemia) and, ultimately, brain damage. In this study, we examined whether methanol extract of the whole plant of Cassia mimosoides var. nomame Makino that grows naturally in Korea, as well as Japan and China, and some of its fractions obtained by partitioning with organic solvents could protect human hepatocellular carcinoma cells (HepG2) under hypoxic condition by inhibiting apoptosis. We also investigated if these extracts could attenuate brain damage in a rat model of 2 hr of ischemia, generated by middle cerebral artery occlusion, and 22 hr of reperfusion. The whole extract ($100{\mu}g$/mL) maintained the cell number at more than half of that initially plated, even after 24 hr of cell culture under hypoxic condition (3% $O_2$). In the absence of the whole extract, almost all of the cells were dead by this time point. This improvement of cell viability came from a delay of apoptosis, which was confirmed by observing the timing of the formation of a DNA ladder when assessed by gel electrophoresis. Of fractions soluble in hexane, ethyl acetate (EA), butanol and water, EA extracts were selected for the animal experiments, as they improved cell viability at the lowest concentration ($10{\mu}g$/mL). The whole extract (200 mg/kg) and EA extract (10 and 20 mg/kg) significantly reduced infarct size, a measure of brain damage, by 34.7, 33.8 and 45.2.0%, respectively, when assessed by 2,3,5-triphenyl tetrazolium chloride staining. The results suggest that intake of Cassia mimosoides var. nomame Makino might be beneficial for preventing ischemic stroke through inhibition of brain cell apoptosis.