• Food Science of Animal Resources
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• v.37 no.4
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• pp.529-534
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• 2017

Probiotics have been known to reduce high-fat diet (HFD)-induced metabolic diseases, such as obesity, insulin resistance, and type 2 diabetes. We recently observed that Lactobacillus acidophilus NS1 (LNS1), distinctly suppresses increase of blood glucose levels and insulin resistance in HFD-fed mice. In the present study, we demonstrated that oral administration of LNS1 with HFD feeding to mice significantly reduces hepatic expression of phosphoenolpyruvate carboxykinase (PEPCK), a key enzyme in gluconeogenesis which is highly increased by HFD feeding. This suppressive effect of LNS1 on hepatic expression of PEPCK was further confirmed in HepG2 cells by treatment of LNS1 conditioned media (LNS1-CM). LNS1-CM strongly and specifically inhibited $HNF4{\alpha}-induced$ PEPCK promoter activity in HepG2 cells without change of $HNF4{\alpha}$ mRNA levels. Together, these data demonstrate that LNS1 suppresses PEPCK expression in the liver by regulating $HNF4{\alpha}$ transcriptional activity, implicating its role as a preventive or therapeutic approach for metabolic diseases.

• Korean Journal of Pharmacognosy
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• v.28 no.2
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• pp.88-92
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• 1997

The full NMR assignment of hispidulin 7-0-neohesperidoside (1) isolated from Cirsium japonicum var. ussuriense was made with the aid of 2D correlation NMR techniques such as HMQC and HMBC. To investigate detoxification of bromobenzene-induced hepatic lipid peroxidation by compound 1, hepatic lipid peroxide level and the activities of enzymes responsible for production and removal of epoxide were studied. The level of lipid peroxide elevated by bromobenzene was significantly reduced by compound 1. This compound administered daily over one week before intoxication with bromobenzene did not affect the activities of aminopyrine N-demethylase, aniline hydroxylase, glutathione S-transferase. Epoxide hydrolase activity was decreased significantly by bromobenzene, which was restored to the control level by pretreatment of persicarin. The results suggest that the bromobenzene-induced hepatic lipid peroxidation by compound 1 is reduced by enhancing the activity of epoxide hydrolase, an enzyme removing bromobenzene epoxide.

• Toxicological Research
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• v.32 no.1
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• pp.15-20
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• 2016

Physiologically based pharmacokinetic (PBPK) modeling can provide an effective way to utilize in vitro and in silico based information in modern risk assessment for children and other potentially sensitive populations. In this review, we describe the process of in vitro to in vivo extrapolation (IVIVE) to develop PBPK models for a chemical in different ages in order to predict the target tissue exposure at the age of concern in humans. We present our on-going studies on pyrethroids as a proof of concept to guide the readers through the IVIVE steps using the metabolism data collected either from age-specific liver donors or expressed enzymes in conjunction with enzyme ontogeny information to provide age-appropriate metabolism parameters in the PBPK model in the rat and human, respectively. The approach we present here is readily applicable to not just to other pyrethroids, but also to other environmental chemicals and drugs. Establishment of an in vitro and in silico-based evaluation strategy in conjunction with relevant exposure information in humans is of great importance in risk assessment for potentially vulnerable populations like early ages where the necessary information for decision making is limited.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.67-67
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• 1995

Acyl-CoA:cholesterol acyltransferase (ACAT, EC 2.3.1.26) plays an important role in the control of intracellular free cholesterol content via its cholesterol esterifying activity. ACAT inhibitors are expected to be effective for treatment of atherosclerosis and hypercholesterolemia. In the course of a screening program for ACAT inhibitors from microbial sources, GERI-BP001 M, A, and B were isolated from the fermentation broth of a fungal strain. GERI-BP001 compounds were isolated from a culture broth of Aspergillus fumigatus F37 by acetone extraction, EtOAc extraction, SiO$_2$ column chromatography, and reverse phase HPLC. The structure of GERI-BP001 coumpounds were determined by $^1$H-NMR, $\^$l3/C-NMR, 2D-NMR, NOESY, and long range C-H COSY experiments. GERI-BP001 M, A, and B inhibit ACAT activity in an enzyme assay system using rat liver microsomes by 50% at concentrations of 75, 147, and 71 ${\mu}$M, respectively.

• Journal of the Korean Society of Food Science and Nutrition
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• v.24 no.5
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• pp.651-657
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• 1995

The antioxidative activity of each fraction in human milk was examined using H2O2 and FeSO4-induced lipid peroxidation of mouse liver homogenate in order to elucidate the antioxidative substances of human milk. High molecular weight(~>20KD) fraction had more antioxidative effect on lipid peroxidation than low molecular weight(~ <20KD) fraction. Furthermore, the changes of antioxidative enzyme activities were estimated during lactation to study the roles of human milk. The human milk showed high activities of catalase, glutathione(GSH) peroxidase and GSH S-transferase. These results suggest that the antioxidative activities may mostly be attributed to high molecular weight fraction containing catalase, GSH peroxidase and GSH S-transferase.

• Proceedings of the Korean Society of Postharvest Science and Technology of Agricultural Products Conference
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• 2003.10a
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• pp.164.1-164
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• 2003

In this study, medium-chain fatty acid (MCFA) metabolized in the liver for quick energy and CLA exhibited biological activity were used for synthesis of structured lipids (SLs). SLs were synthesized by acidolysis of soybean oil, capric acid (C10:0) and CLA with Chirazyme L-2 lipase as biocatalysts. The effect of enzyme load (2, 4, 6, 8, 10% w/w substrates) was investigated. Production of SL (scale-up) was performed with a 1:2:2 molar ratio (oi1/C10:0/CLA) for 24 h at 55$^{\circ}C$ in a stirred batch reactor (420 rpm). The reaction was catalyzed by Chirazyme L-2 lipase (24.48g, 4％ w/w substrates). The scale-up result showed that capric acid and total CLA were incorporated 4.9%, 4.1% (mole%), respectively, in soybean oil. Then, physio-chemical property and flavor characteristic of produced SL-soybean oil were analyzed. Therefore, SL-soybean oil containing C10:0 and CLA was successfully synthesized and may be beneficial in desirable food and nutritional applications.

• Journal of Integrative Natural Science
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• v.7 no.4
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• pp.241-252
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• 2014

A series of N-benzoylated ligands incorporating three different benzoyl groups 2,2'-(benzoyliminodiethylene)-4-substituted phenols ($L^{1,4,7}$), 2,2'-(4-nitrobenzoyliminodiethylene)-4-substituted phenols ($L^{2,5,8}$) and 2,2'-(3,5-dinitrobenzoyliminodiethylene)-4-substituted phenols ($L^{3,6,9}$) were synthesized and characterized by IR, $^1H$ NMR, $^{13}C$ NMR and mass spectroscopy. The In vitro antibacterial activity of investigated ligands were tested against human pathogenic bacteria such as four Gram (-) Enterococcus faecalis, Pseudomonas aeruginosa, Staphylococcus aureus, Vibrio cholera, Vibrio harveyi and two Gram (+) Staphylococcus aureus, Streptococcus mutans. Furthermore, docking studies were undertaken to gain insight into the possible binding mode of these compounds with the binding site of the topoisomerase II (PDB: 4FM9) enzyme which is involved in DNA superhelicity and chromosome seggregation. The N-benzoylated derivatives $L^{5,7,8}$ have significant anticancer activity as Topoisomerase inhibitors. The ligands $L^5$ and $L^8$ were tested for their anticancer activity against human liver adenocarcinoma (HepG2) cell line with the MTT assay.

• Korean Journal of Community Nutrition
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• v.9 no.4
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• pp.536-544
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• 2004

To evaluate the antioxidative effect of maengjong-juk (Phyllostachys pubescens) extract coated rice in vivo system, maengjong-juk extract coated rice diets were fed to C57BL/6 mice for 16 weeks. Plasma total antioxidative capacity, hepatic lipid peroxidation, protein oxidation, activities of antioxidative enzymes and total glutathione content were measured. Plasma total antioxidative capacity was elevated significantly in maengjong-juk extract diets supplemented group in a dose dependant manner. Hepatic TBARS contents were significantly decreased in maengjong-juk extract diets supplemented group compared to high cholesterol group. Maengjong-juk extract coated rice diets suppressed the protein oxidation significantly in liver. Activities of hepatic antioxidative enzymes such as total SOD, CuㆍZn-SOD, Mn-SOD, GSH-Px and catalase activities of maengjong-juk extract coated rice diets were significantly higher than those of high cholesterol diet. Total hepatic glutathione content was significantly increased by maengjong-juk extract coated rice diets administration. According to this study, numerous antioxidative materials and phytochemicals containing in maengjong-juk extracts appear to protect antioxidative systems in C57BL/6 mice fed bamboo extract coated rice diet. (Korean J Community Nutrition 9(4): 536∼544, 2004)

• Korean Journal of Clinical Pharmacy
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• v.29 no.4
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• pp.223-230
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• 2019

Background: Small-molecule tyrosine kinase inhibitors (TKIs) have had major impacts on anticancer therapy by targeting the catalytic activities of dysregulated tyrosine kinases. TKIs have not presented traditional toxicities; however, some serious adverse effects, including hepatotoxicity, have been documented in clinical trials and post-marketing surveillance. Although TKI-induced hepatotoxicity can cause severe clinical complications in patients, the underlying mechanism is still unclear. Methods: Studies on TKI-induced hepatotoxicity were identified by Pubmed search, and relevant articles were reviewed. Results: Immunoallergic reaction, cytochrome P (CYP) 450 polymorphisms, and formation of reactive metabolites are under consideration as mechanisms of TKI-induced hepatotoxicity. Host protein-drug metabolite conjugates are recognized as antigens by class II major histocompatibility complexes and are believed to cause liver injuries. Polymorphisms in CYP, which influences TKI metabolism, can slow TKI metabolism and may induce development of hepatotoxicity. The formation of reactive metabolites during drug metabolism can induce hepatotoxicity by directly causing cytotoxicity, leading to cell dysfunction, and indirect toxicity by mediating secondary immune reactions. Concurrent use of various medications with TKI can also cause hepatotoxicity by affecting drug transporter or enzyme activities. Conclusion: Periodic monitoring of patients taking TKIs and risk/benefit reassessments though post marketing surveillance are necessary to prevent hepatotoxicity.

• Journal of Integrative Natural Science
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• v.9 no.3
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• pp.190-198
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• 2016

Xanthine Oxidase is an enzyme, which oxidizes hypoxanthine to xanthine, and xanthine to uric acid. It is widely distributed throughout various organsincluding the liver, gut, lung, kidney, heart, brain and plasma. It is involved in gout pathogenesis. In this study, we have performed Comparative Molecular Field Analysis (CoMSIA) on a series of 2-(indol-5-yl) thiazole derivatives as xanthine oxidase (XO) inhibitors to identify the structural variations with their inhibitory activities. Ligand based CoMSIA models were generated based on atom-by-atom matching alignment. In atom-by-atom matching, the bioactive conformation of highly active molecule 11 was generated using systematic search. Compounds were aligned using the bioactive conformation and it is used for model generation. Different CoMSIA models were generated using different alignments and the best model yielded across-validated $q^2$ of 0.698 with five components and non-cross-validated correlation coefficient ($r^2$) of 0.992 with Fisher value as 236.431, and an estimated standard error of 0.068. The predictive ability of the best CoMSIA models was found to be $r{^2}_{pred}$ 0.653. The study revealed the important structural features required for the biological activity of the inhibitors and could provide useful for the designing of novel and potent drugs for the inhibition of Xanthine oxidase.