• Biomolecules & Therapeutics
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• v.26 no.1
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• pp.39-44
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• 2018

In 1923, Dr. Warburg had observed that tumors acidified the Ringer solution when 13 mM glucose was added, which was identified as being due to lactate. When glucose is the only source of nutrient, it can serve for both biosynthesis and energy production. However, a series of studies revealed that the cancer cell consumes glucose for biosynthesis through fermentation, not for energy supply, under physiological conditions. Recently, a new observation was made that there is a metabolic symbiosis in which glycolytic and oxidative tumor cells mutually regulate their energy metabolism. Hypoxic cancer cells use glucose for glycolytic metabolism and release lactate which is used by oxygenated cancer cells. This study challenged the Warburg effect, because Warburg claimed that fermentation by irreversible damaging of mitochondria is a fundamental cause of cancer. However, recent studies revealed that mitochondria in cancer cell show active function of oxidative phosphorylation although TCA cycle is stalled. It was also shown that blocking cytosolic NADH production by aldehyde dehydrogenase inhibition, combined with oxidative phosphorylation inhibition, resulted in up to 80% decrease of ATP production, which resulted in a significant regression of tumor growth in the NSCLC model. This suggests a new theory that NADH production in the cytosol plays a key role of ATP production through the mitochondrial electron transport chain in cancer cells, while NADH production is mostly occupied inside mitochondria in normal cells.

• Applied Biological Chemistry
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• v.44 no.3
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• pp.208-210
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• 2001

• YAKHAK HOEJI
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• v.57 no.4
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• pp.241-249
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• 2013

We reported previously that the extracts of Yacon tuber and leaf have spermatogenic activity and testosterone level increasing effect in men. The aim of this study was to investigate the mechanism of testosterone level increasing effect of Yacon tuber and leaf extracts. In this study, we found that Yacon leaf extracts and chlorogenic acid, a constituent of Yacon extracts showed significantly inhibition effect of testosterone degradation in rat liver homogenate. We suggest that this could be a part of direct mechanism about increasing effect of testosterone level. Futhermore, we evaluated the inhibition effect of testosterone metabolism of Torilis japonica and Coix lacryma-jobi have been reported as $5{\alpha}$-reductase inhibitor. The inhibition ratio of testosterone metabolism of these were Torilis japonica>Coix lacryma-jobi>Yacon. We also evaluated the benign prostatic hyperplasia (BPH) score with the preparation composed of these natural product, Yacon pill. It showed the decreased the BPH score in men. Rats with BPH showed significantly increased dihydrotestosterone (DHT) levels in the serum; however, Yacon pill extracts treated rats showed significant reduction of DHT levels compared with the BPH group. Conclusively, Yacon pill showed the possibility as ameliorable agents of BPH symptoms.

• Toxicological Research
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• v.11 no.1
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• pp.1-8
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• 1995

Fumonisins are a family of mycotoxins produced by the fungus Fusarium moniliforme which is a common contaminant in corn. Fumonisins are potent inhibitors of sphingosine and sphinganine N-acyltransferase (ceramide synthase), key enzymes in sphingolipid metabolism. The purpose of this study was to provide the evidence that the elevated levels of free sphingoid bases (primarily sphinganine) and depletion of complex sphingolipids were closely related to the inhibition of cell growth in LLC-$PK_1$ cells exposed to fumonisin $B_1$$(\leq 35 {\mu}M)$. Concentrations of fumonisin $B_1$ between 10 and $35 {\mu}M$ were known to inhibit cell growth without cytotoxicity in $LLC-PK_1$ cells (Yoo et al. Toxicol. Appl. Pharmacol. 114, 9-15, 1992). Cells exposed to 35$\mu M$ fumonisin B$_1$ for 48 and 72 hr developed a fibroblast-like (elongated and spindle-shaped) appearance and were less confluent than normal cells. At between 24 and 48 hr after exposure to fumonisin $B_1$ cells were beginning to show the inhibition of cell growth and at 72 hr the number of viable cells in fumonisin-treated cultures was about 50% of concurrent control cultures. During the 24 hr lag period preceding inhibition of cell growth, the free sphinganine levels in cells exposed to $35 {\mu}M$ fumonisin $B_1$ were highly elevated (approximately 230 fold higher than normal cells). The elevated levels of free sphinganine were $435\pm14$$pmoles/{10^6}$ cells at 48 hr and approximately TEX>$333\pm11$$pmoles/{10^6}$ cells in cells exposed to $35{\mu}M$ fumonisin$B_1$ at 72 hr, while the levels of free sphinganine in normal cells were less than 2$pmoles/{10^6}$ cells. Under the same condition, depletion of intracellular complex sphingolipids as a consequence of fumonisin inhibition of de novo sphingolipid biosynthesis and turnover pathway was appeared. Content of free sphingold bases in dividing cells was more elevated than in confluent cells at 24-48 hr after cells were exposed to $20{\mu}M$ fumonisin $B_1$. The dividing cells were showing the inhibition of cell growth at 48-72 hr and $20{\mu}M$ fumonisin $B_1$. The results of this study support the hypothesis that the inhibition of cell growth is very well related to the disruption of sphingolipid metabolism in $LLC-PK_1$ cells.

• Biomolecules & Therapeutics
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• v.1 no.1
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• pp.71-76
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• 1993

It has been reported that d-limonene inhibits chemical-induced rat mammary cancer by the mechanism of increases in detoxification enzymes such as glutathione S-transferases and that cineole fails to exhibit significant suppressive effect on chemical-induced carcinogenesis. The present study was designed to compare the effects of d-limonene and cineole on the benzo(a)pyrene (BP)-induced mutagenicity, BP metabolism and lipid peroxidation. Modified Ames assay was employed to evaluate the inhibitory effect of d-limonene and cineole on the BP-induced mutagenicity. The number of revertant-bearing wells was decreased by 44~77% in the presence of both BP and d-limonene compared with that of BP alone whereas cineole decreased the number of revertant-bearing wells by 28~45% at the concentrations between $2{\mu}m$m.TEX> and 2 mM. d-Limonene suppressed BP metabolism by 16, 54 and 67% at 1, 10 and 100 mM, respectively while cineole inhibited the metabolism by 16, 26 and 55% at the same concentrations. The $EC_{50}$ values for d-limonene and cineole in inhibiting lipid peroxidation were 2.0 mM and 16 mM respectively, as assayed by thiobarbituric acid method. The present study showed that d-limonene and cineole have common antimutagenic effects although d-limonone appeared to be more effective than cineole in suppressing mutation and lipid peroxidation. The results suggest that the antimutagenic effects of d-limonene and cineole may be associated with alternation in enzyme activities and with inhibition of lipid peroxidation.

• Archives of Pharmacal Research
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• v.28 no.10
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• pp.1156-1160
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• 2005

An iridoid glycoside, oldenlandoside III (5) was isolated from the n-butanol fraction of methanol extracts of the aerial parts of Oldenlandia diffusa Roxb. along with six others previously characterized iridoid glycosides; geniposidic acid (1), scandoside (2), feretoside (3), 10-O-ben-zoylscandoside methyl ester (4), asperulosidic acid (6) and deacetylasperulosidic acid (7). Compounds 1, 2, and 7 inhibited LDL-oxidation, and showed $63.3{\pm}2.0,\;62.2{\pm}1.6,\;and\;63.8{\pm}1.5\%$ inhibition, respectively, at a concentration of 20 ${\mu}g/mL$.

• YAKHAK HOEJI
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• v.43 no.4
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• pp.481-486
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• 1999

Excessive or long term ingestion of alcohol may cause hepatitis, cirrhosis, hepatic tumor and so on. Aldehyde and active form of free oxygen that are metabolites of alcohol in liver are the cause of liver cell damage. The main system of alcohol metabolism is composed of alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH) and cytochrome P450. In connection with in vivo alcohol metabolism, more than one hundred natural products were screened for inhibition or activation of alcohol dehydrogenase. As a results, we found significant inhibition ($IC_50$) of ADH by methanolic extracts of Puerariae Radix ($61.2{\;}\mu\textrm{g}/ml$), Glycyrrhizae Radix ($105.0{\;}\mu\textrm{g}/ml$), Cinnamomi Ramulus ($7.0{\;}\mu\textrm{g}/ml$), Rhei Rhizoma ($36.7{\;}\mu\textrm{g}/ml$), Mori Cortex Radicis ($106.2{\;}\mu\textrm{g}/ml$), Chrysanthemi Flos ($112.2{\;}\mu\textrm{g}/ml$), Erycibes Caulis ($36.7{\;}\mu\textrm{g}/ml$), and Scutellariae Radix ($122.5{\;}\mu\textrm{g}/ml$)

• Toxicological Research
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• v.22 no.1
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• pp.1-8
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• 2006

The primary metabolism of pyribenzoxim was studied in rat liver microsomes in order to identify the cytochrome P450 (CYP) isoform(s) and esterases involved in the metabolism of pyribenzoxim. Chemical inhibition using CYP isoform-selective inhibitors such as ${\alpha}$-naphthoflavone, tolbutamide, quinine, chlorzoxazone, troleandomycin, and undecynoic acid indicated that CYP1A and CYP2D are responsible for the oxidative metabolism of pyribenzoxim. And inhibitory studies using eserine, bis-nitrophenol phosphate, dibucaine, and mercuric chloride indicated pyribenzoxim hydrolysis involved in microsomal carboxylesterases containing an SH group (cysteine) at the active center.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.10a
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• pp.196-196
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• 2001

Stereoselective metabolism and inhibitory potential of lansoprazole enantiomers were evaluated from the incubational studies of human liver microsomes and eDNA-expressed CYP isoforms in vitro. The formation of lansoprazole sulfone from both enantiomers appeared to be catalyzed by single and low affinity enzyme. Lansoprazole 5-hydroxylation, however, appeared to be mediated by two kinetically distinct CYP enzymes.(omitted)

• Biomolecules & Therapeutics
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• v.30 no.1
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• pp.1-18
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• 2022

Drug-drug interactions are a major cause of hospitalization and deaths related to drug use. A large fraction of these is due to inhibition of enzymes involved in drug metabolism and transport, particularly cytochrome P450 (P450) enzymes. Understanding basic mechanisms of enzyme inhibition is important, particularly in terms of reversibility and the use of the appropriate parameters. In addition to drug-drug interactions, issues have involved interactions of drugs with foods and natural products related to P450 enzymes. Predicting drug-drug interactions is a major effort in drug development in the pharmaceutical industry and regulatory agencies. With appropriate in vitro experiments, it is possible to stratify clinical drug-drug interaction studies. A better understanding of drug interactions and training of physicians and pharmacists has developed. Finally, some P450s have been the targets of drugs in some cancers and other disease states.