• Journal of Microbiology and Biotechnology
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• v.15 no.1
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• pp.183-187
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• 2005

Abstract The cancer chemopreventive potential of chitosanoligosaccharides was investigated by measuring the induction of quinone reductase and glutathione S-transferase activities and inhibition of cytochrome P450 1A1, 2B1, and 2E1 activities. Chitosanoligosaccharide I (1-${\kappa}$Da${\kappa}$Da) significantly induced glutathione S-transferase activity with a maximal 1.5-fold increase at 500 ${\mu}$g/ml, while chitosanoligosaccharide II (3-${\kappa}$Da${\kappa}$Da) (500 ${\mu}$g/ml) strongly induced quinone reductase (p<0.01) and glutathione S-transferase (p<0.005) activities. The in vitro incubation of rat liver microsomes with chitosanoligosaccharides I and II (2.5, 5, 50, and 500 ${\mu}$g/ml) showed a dose-dependent inhibiton of cytochrome P450 1A1, 2B1, and 2E1 activities. Chitosanoligosaccharide II was a more potent inhibitor of cytochrome P450 2B1 activity than chitosanoligosaccharide I. Accordingly, these findings suggest that chitosanoligosaccharides are potential chemopreventive agents.

• 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 Microbiology and Biotechnology
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• v.18 no.11
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• pp.1785-1788
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• 2008

Phenylpyropenes A, B, and C, isolated from Penicillium griseofulvum F1959, inhibited DGAT in rat liver microsomes with $IC_{50}$ values of $78.7{\pm}1.6$, $21.7{\pm}0.2$, and $11.04{\pm}0.2{\mu}M$, respectively. In addition, a kinetic analysis using a Lineweaver-Burk plot revealed that phenylpyropene C was a noncompetitive inhibitor of DGAT. The apparent Michaelis constant ($K_m$) value and inhibition constant ($K_i$) value were calculated to be $8{\mu}M$ and $10.48{\mu}M$, respectively. Moreover, phenylpyropene C inhibited triglyceride formation in HepG2 cells.

• Archives of Pharmacal Research
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• v.26 no.10
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• pp.800-804
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• 2003

The effects of KR-31378, a neuroprotective agent for ischemia-reperfusion damage, on liver microsomal cytochrome P450s (CYPs) were investigated in male Sprague Dawley rats. When rats were treated orally with KR-31378 for 7 consecutive days, CYP3A-selective erythromycin N-demethylase (ERDM) activity was significantly induced in a dose-dependent manner. In Western immunoblotting, CYP 3A proteins were clearly induced by treatment with KR-31378. Within 24 h after treatment with 80 mg/kg of KR-31378, ERDM activity was induced in liver microsomes in accompanied by induction of the level of CYP 3A proteins. The present results suggest that KR-31378 might modulate the expression of CYP 3A enzymes in humans.

• Archives of Pharmacal Research
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• v.23 no.5
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• pp.461-466
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• 2000

Tectorigenin and kaikasaponin III from the flowers of Pueraria thunbergiana showed potent hypoglycemic and hypolipidemic effects in the streptozotocin-induced diabetic rats. Intraperitoneal administration of these two compounds with 5 and 10 mg/kg, respectively, for seven days to streptozotocin-induced rats significantly reduced the blood glucose, total cholesterol, LDL- and VLDI-cholesterol and triglyceride levels when compared with those of control group. Glycitein in which 5-OH is unlinked and tectoridin (7-O-glycoside of tectorigenin) isolated from the flowers of P. thunbergiana did not improve hyperglycemia and hyperlipidemia. In addition, tectorigenin showed in vitro antioxidant effects on 1,1-diphenyl-B-pirylhydrazyl (DPPH) radical, xanthine-xanthine oxidase superoxide anion radical, and lipid peroxidation in rat microsomes induced by enzymatic and non-enzymatic methods. We further found that tectorigenin and kaikasaponin III protected the Vero cell line(normal monkey kidney) from injury by hydrogen peroxide. From these findings, it seems likely that the antioxidant action of tectorigenin and kaikasaponin III may alleviate the streptozotocin-induced toxicity and contribute to hypoglycemic and hypolipidemic effects.

• YAKHAK HOEJI
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• v.40 no.5
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• pp.563-573
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• 1996

The system most likely responsible for the accelerated metabolism of alcohol with chronic ingestion or at high blood ethanol levels, is the microsomal ethanol-oxidizing system(M EOS). While the increase in the MEOS with chronic ethanol ingestion is thought to be adaptive, it may also have serious adverse effects on the liver. The rates of the NADPH-dependent oxygen consumption by the liver microsomes from the prolonged ethanol fed rats were 2 times higher than the rates from the non-treated rats. With the alcohol ingestion, the total SH and nonprotein SH contents showed the significant decrease and at the same time, MDA in liver and GOT and GPT levels in blood showed the significant increase, which suggests the occurrence of liver damage due to the oxidative stress caused by chronic alcohol consumption. The mitochondrial aldehyde dehydrogenase(ALDH) activity was decreased by chronic ethanol ingestion, whereas the alcohol dehydrogenase activity and the cytosolic ALDH activity were not altered. These results suggest that the induction of cytochrome P450 by the chronic alcohol ingestion increases the oxidative stress which seems to result in the altered the physiological states of the liver including the ALDH activity, which may in turn to lead to the liver disease.

• Journal of Environmental Health Sciences
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• v.19 no.3
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• pp.58-63
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• 1993

In order to elucidate the alteration of drug-metabolizing enzymes and mechanism in the animal with hepatic injury and ketosis, the regulation of P450IIE was studied in the rats with heaptic injury caused by CCl$_4$ and with ketosis caused by streptozotocin and high-fat diet. P450IIE expression in liver was examined by the combination of enzyme activities, Western immunoblot, and mRNA Northern blot analyses using specific polyclonal antibody and cDNA probe for P450IIE. Enzyme activity and amounts of immunoreactive P450IIE were rapidly decreased in a time-dependent manner after a single dose of CCl$_4$ . However, the decreases in P450IIE enzyme activity and immunoreactive protein by CCl$_4$ were not accompanied by a decline in its mRNA level. The data thus suggested a post-translational reduction of P450IIE by CCl$_4$. The enzyme activities (aniline hydroxylase) in hepatic microsomes were elevated about 2-3-fold by streptozotocin and feeding with a high fat diet. This increases in enzyme activities were also accompanied by 3-fold increases in immunoreactive P450IIE protein and its mRNA. Our data thus indicated that P450IIE induction during the ketosis appears to be due to pretranslational activation.

• Archives of Pharmacal Research
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• v.8 no.3
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• pp.119-132
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• 1985

The apparent effectiveness of 1-naphthyl-N-methyl carbamate (carbaryl) against a wide variety of insects motivated the study of its mammalian toxicity. In this toxicological study of carbaryl, mature male rats inhaled carbaryl at a mean concentration of 112mg, 168mg and 224 mg/$m^{3}$ for one hour. After inhalation, pentobarbital sleeping time, Nadph-cytochrome c reductase activity, cytochrome p-450 and protein content in liver microsomes, various tissue residues, cholinesterase inhibition in plasma and histopathological findings at autopsy were observed. The pentobarbital sleeping time was prolonged in rats inhaled with carbaryl for one day while the sleeping time was shortened in the 3 days inhaled group. The changes of cytochrome p-450 content and NADPH-cytochrome c reductase activity exhibited biphasic response showing the decrease in the one day inhaled group and the increase in the 3 days inhaled group. The marked depression of plasma ChE activity was observed in rats inhaled with carbaryl at 112 mg/$m^{3}$, however no more progressive effect was observed at the higher concentration of the compound. The main observations in histopathological finding were ciliary detachment, epithelial swelling and subepithelial inflammatory cellular infiltration in trachea due to the irritation.

• The Korean Journal of Food And Nutrition
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• v.32 no.5
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• pp.417-424
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• 2019

The purpose of this study was to observe the effects of the polysaccharide (GLP) obtained from the liquid cultured Ganoderma lucidum on the lipidperoxidation in a rat liver microsome and hepatotoxicity in the primary cultured rat hepatocytes. It is well known that the polysaccharide of Ganoderma lucidum exhibits hepatoprotective activity, antitumor activity etc., which many suggest a relationship to lipidperoxidation. The effect of GLP on $CCl_4-$ and galactosamineintoxicated cytotoxicity in the primary cultured rat hepatocytes were reduced the GPT value. In order to the estimate the effects of anti-lipidperoxidation of the polysaccharide, enzymatic and nonenzymatic reaction assays were performed, in vitro, in the rat liver microsome. An enzymatic lipidperoxidation reaction by $ADP+FeCl_3+NADPH$ and $CCl_4+NADPH$, GLP (1 mg/mL) inhibited 77.4% and 39.4%, respectively, and the nonenzymatic reaction displayed a 97.4% strongly inhibition. In the enzymatic and nonenzymatic inducers treated with GLP, the formation of malondialdehyde (MDA) progressively decreased by raising the GLP concentration. These results suggest that the anti-lipidperoxidation and radical scavenging activity of GLP may play an important part in the liver protection action.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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• pp.100-100
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• 1997

To treat peptic ulcer diseases, many potent proton pump inhibitors have been developed for suppressing the gastric acid secretion in clinical patients. However, most of these agents have common irreversible mechanisms against H$\^$+/, K$\^$+/-ATPase which might be the cause of hypergastrinemia and ECL cell hyperplasia. Therefore, the development of new reversible inhibitors is prompted. In this study, we investigated the inhibitory mechanism of a newly synthesized proton pump inhibitor, YJA20379-8 using lyophilized hog gastric microsomes. YJA20379-8 inhibited K$\^$+/-stimulated H$\^$+/K$\^$+/-ATPase activity uncompetitively with respect to K$\^$+/, and in the other hand, showed competitive inhibitory pattern with ATP, respectively. From these data, we suggest that YJA20379-8 may be a proton pump inhibitor with a new inhibitory mechanism.