• Archives of Pharmacal Research
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• v.24 no.1
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• pp.16-20
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• 2001

2-(Allylthio)pyrazine derivatives were designed as a novel cancer chemopreventive agent that functions through selective inhibtion of cytochrome P-450 and induction of phase 11 enzymes involved in the detoxification of carcinogens. A practical preparation method of 2-(allylthio) pyrazine derivatives was established by the reaction of 2-mercaptopyrazine and allylbromides in the presence of a catalytic antioxidant, DABCO (1,4-diazabicyclo[2,2,2] octane), in dimethyl-formamide at below $50^{\circ}C$.

• 한국균학회소식:학술대회논문집
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• 2014.05a
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• pp.25-25
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• 2014

Koji molds are comprised of yellow, black and white. Black and white koji molds were recently re-visited by this author and it is concluded that they consists of Aspergillus luchuesnsis, A. niger and A. tubingensis, and the most important species for alcoholic beverage production is A. luchuensis. In the case of yellow koji mold, it is comprised of Aspergillus oryzae, A. sojae and A. tamari. In the case of A. sojae, the species is scarcely isolated from nature and rarely used for industry in Korea. Aspergillus tamari is often isolated from traditional Korean Meju, a fermented soybean product, and the classification of the species is clear. However, in the case of A. oryzae, differentiation between A. oryzae and A. flavus is still in controversy. In this study, we collected 415 strains of Aspergillus flavus/oryzae complex from air, rice straw, soybean, corn, peanut, arable soil and Meju in Korea and we examined the aflatoxin producing capacity of the strains. The norB-cypA, omtA and aflR genes in the aflatoxin biosynthesis gene cluster were analyzed. We found that 367 strains (88.4%) belonged to non-aflatoxigenic group (Type I of norB-cypA, IB-L-B-, IC-AO, or IA-L-B- of omtA, and AO type of aflR), and only 48 strains (11.6%) belonged to aflatoxin-producible group (Type II of norB-cypA, IC-L-B+/B- or IC-L-B+ of omtA, and AF type of aflR). In the case of A. flavus/oryzae strains from Meju, almost strains (178/192, 92.7%) belonged to non-aflatoxigenic group and only 14 strains (7.3 %) belonged to aflatoxin-producible group. It is proposed in this study that non-aflatoxigenic strain from Meju is classified as A. oryzae, considering that Meju is food material.

• Environmental Analysis Health and Toxicology
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• v.31
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• pp.10.1-10.8
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• 2016

Objectives Aromatase inhibitors that block estrogen synthesis are a proven first-line hormonal therapy for postmenopausal breast cancer. Although it is known that standardized extract of Ginkgo biloba (EGb761) induces anti-carcinogenic effects like the aromatase inhibitors, the effects of EGb761 on steroidogenesis have not been studied yet. Therefore, the effects of EGb761 on steroidogenesis and aromatase activity was studied using a H295R cell model, which was a good in vitro model to predict effects on human adrenal steroidogenesis. Methods Cortisol, aldosterone, testosterone, and $17{\beta}$-estradiol were evaluated in the H295R cells by competitive enzyme-linked immunospecific assay after exposure to EGb761. Real-time polymerase chain reaction were performed to evaluate effects on critical genes in steroid hormone production, specifically cytochrome P450 (CYP11/ 17/19/21) and the hydroxysteroid dehydrogenases ($3{\beta}$-HSD2 and $17{\beta}$-HSD1/4). Finally, aromatase activities were measured with a tritiated water-release assay and by western blotting analysis. Results H295R cells exposed to EGb761 (10 and $100{\mu}g/mL$) showed a significant decrease in $17{\beta}$-estradiol and testosterone, but no change in aldosterone or cortisol. Genes (CYP19 and $17{\beta}$-HSD1) related to the estrogen steroidogenesis were significantly decreased by EGb761. EGb761 treatment of H295R cells resulted in a significant decrease of aromatase activity as measured by the direct and indirect assays. The coding sequence/Exon PII of CYP19 gene transcript and protein level of CYP19 were significantly decreased by EGb761. Conclusions These results suggest that EGb761 could regulate steroidogenesis-related genes such as CYP19 and $17{\beta}$-HSD1, and lead to a decrease in $17{\beta}$-estradiol and testosterone. The present study provides good information on potential therapeutic effects of EGb761 on estrogen dependent breast cancer.

• The Journal of Korean Medicine
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• v.30 no.4
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• pp.129-141
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• 2009

Objective: This study was to investigate the anti-tumor effect, safety, safety, mechanism and metabolizing enzyme of Agrimonia pilosa LEDEB (APL) in female C57B/L mouse tumor (in vivo). Method: First, to evaluate the antitumor activity of APL, we divided the mice into four groups: normal, control, APL50 (50mg/kg), and APL100 (100mg/kg). LLC-obtained American Type Culture Collection was used. LLC had been inoculated to induce tumors. To measure the anti-tumor effect of APL, we calibrated tumor size and weight. To analyze the mechanism of anti-tumor in APL, we used western blotting and to observe metabolizing enzyme in APL we used to real-time PCR. Result: APL50 and APL100 significantly inhibited tumor growth from 12 days after medicine injected. APL did not induce caspase-dependent apoptosis in LLC-bearing mouse tumor. In APL100, it decreased 41% and 71% in CYP2D22 and CYP3A11, respectively. Conclusion: These results suggest that APL has some anti-tumor effects in female C57B/L mouse tumor. APL should be used carefully with other drugs related with CYP2D22 and CYP3A11.

• Environmental Analysis Health and Toxicology
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• v.21 no.3 s.54
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• pp.291-299
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• 2006

The experiments investigated whether early exposure to testosterone propionate (TP) during prepuberty alters testis development in Sprague-Dawley male rats. We performed Hershberger assay using the stimulated weanling male rats by OECD protocols, cDNA microarray, and Western blot. TP was subcutaneously injected to uncastrated Sprague-Dawley male rat of 22 days old for 10 consecutive days at doses of 0.4, 0.8, 1.0, 1.2, 1.6 mg/kg per day. At necropsy, the following tissues were removed and weighed: combined testes, epididymides (Epi), Cowper's glands (COW), levator am, and bulbocavernosus muscles (LABC), seminal vesicles, together with coagulating gland (SV) and ventral prostate (VP). We found that TP increased the weights of Epi, VP, SV, COW, and LABC, while testis was decreased in a dose-dependent manner. In cDNA microarray analysis of testis, there were significant reductions in the expression of cytochrome P450 11A (CYP11A), the rate-limiting enzyme of steroidogenesis. Taken together these results, TP exposure before puberty in male rats may produce the delay in testis development by inhibiting the CYP11A gene expression.

• Biomolecules & Therapeutics
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• v.24 no.1
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• pp.40-48
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• 2016

The pregnane X receptor (PXR), a liver and intestine specific receptor,, has been reported to be related with the repression of inflammation as well as activation of cytochromosome P450 3A (CYP3A) expression. We examined the effect of PXR on tetrachloromethane (CCl4)-induced mouse liver inflammation in this work. Ginkgolide A, one main component of Ginkgo biloba extracts (GBE), activated PXR and enhanced PXR expression level, displayed both significant therapeutic effect and preventive effect against $CCl_4$-induced mouse hepatitis. siRNA-mediated decrease of PXR expression significantly reduced the efficacy of Ginkgolide A in treating $CCl_4$-induced inflammation in mice. Flavonoids, another important components of GBE, were shown anti-inflammatory effect in a different way from Ginkgolide A which might be independent on PXR because flavonoids significantly inhibited CYP3A11 activities in mice. The results indicated that anti-inflammatory effect of PXR might be mediated by enhancing transcription level of $I{\kappa}B{\alpha}$ through binding of $I{\kappa}B{\alpha}$. Inhibition of NF-${\kappa}B$ activity by NF-${\kappa}B$-specific suppressor $I{\kappa}B{\alpha}$ is one of the potential mechanisms of Ginkgolide A against CCl4-induced liver inflammation.

• Journal of Korean Medicine for Obesity Research
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• v.4 no.1
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• pp.139-160
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• 2004

The obesity is detrimental to the health of people living in affluent societies. Individual differences in energy metabolism are caused primarily by single nucleotide polymorphisms(SNPs), some of which promote the development of obesity-related type 2 diabetes mellitus. Type 2 diabetes mellitus is a common multifactorial genetic syndrome, which is determined by several different genes and environmental factors. In this review, five major conclusions are reached: (1)To be clinically significant, SNPs must be relevant, prevalent, modifiable, and measurable. (2)Differences in SNPs may have been caused by famine, ultraviolet light, alcohol, climate, agricultural revolution. livestock, lactase persistence, and westernized lifestyle. (3)Candidate obesity genes of calorie intake restriction are SIM 1, MC3R, MC4R, AGRP, CART, CCK, CNTFR, DRD2, Ghrelin, 5-HT receptor, NPY, PON and those of energy metabolism are LEP, LEPR, UCP1, UCP2, UCP3, B2AR, B3AR, PGC-1, Androgen receptor and those of fat mobilization are AGT, ACE, ADA, APM1, Apolipoproteins, PPAR, FABP, FOXC2, GCGR, $11-{\beta}HSDI$, LDLR, Hormonal sensitive lipase, Perilipin, $TNF-{\alpha}$, $TNF-{\beta}$ (4)Candidate obesity genes in the eastern are NPY, LEP, LEPR, UCP1, UCP2, UCP3, B2AR, B3AR, ACE, APM1, PPAR, and FABP. (5)Candidate obesity genes in type 2 diabetes mellitus are MC3R, MC4R, B2AR, B3AR, ADA, APM1, PPAR, FABP, FOXC2, PC1, PC2, ABCC8, CAPN10, CYP19, CYP7, ENPP1, GCK, GYS1, IGF, IL-6, Insulin receptor, IRS, and LPL. The discovery of SNPs will lead to a greater understanding of the pathogenesis of obesity and to better diagnostics, treatment, and eventually prevention.

• The Korean Journal of Mycology
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• v.42 no.3
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• pp.191-200
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• 2014

Nuruk samples collected from various regions in Korea were investigated in terms of fungal contents and diversity. In measurement of colony forming unit (CFU) in Nuruk suspensions on DRBC agar, Nuruk samples MS4, MS8, and MS10 were among the highest fungal density, with $1,278.9{\pm}21.6$ (${\times}10^4$), $1,868.0{\pm}27.7$ (${\times}10^4$), and $775.1{\pm}19.2$ (${\times}10^4$) were among the samples showing the highest fungal density. CFU per 20 mg Nuruk, respectively. The majority of fungal components were yeasts, including Pichia anomala, P. kudriavzevii, Kluyveromyces marxianus, and Saccharomycopsis fibuligera, whereas Aspergillus oryzae and Rhizopus oryzae, the representative Nuruk fungi, were predominant only in the low fungal density Nuruks (MS2, MS5, and MS11). Saccharification capability of the fungal isolates was assessed by measurement of amylase activity in the culture broth. The highest amylase activity was found in A. niger and A. luchuensis, followed by S. fibuligera. A. oryzae and R. oryzae showed fair amylase activity but significantly lower than those of the three fungal species. R. oryzae was suggested to play an additional role in degradation of ${\beta}$-glucan in crop component of Nuruk since R. oryzae was the only fungus that showed ${\beta}$-glucanase activity among the fungal isolates. To confirm the safety of Nuruk, aflatoxigenicity of the isolated Aspergillus was estimated using the DNA markers norB-cypA, aflR, and omtA. All of the isolates turned out to be non-aflatoxigenic as evidenced by the deletion of gene markers, norB-cypA and aflR, and the absence of aflatoxin in the culture supernatants shown by TLC analysis.

• Toxicological Research
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• v.20 no.3
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• pp.195-203
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• 2004

4-Tert-Octylphenol (OP) is a surfactant additive widely used in the manufacture of a variety of detergents and plastic products. OP can disrupt endocrine function in humans and animals. This study was carried out to obtain toxicokinetic parameters of OP in male Sprague-Dawley (SD) rats. Male rats were administered with OP by single oral application of 200 mg/kg body weight. Blood, urine and tissues samples were taken at several time intervals after administration. Analysis of samples for OP was performed by column-switching high performance liquid chromatography (HPLC). In addition, we exam-ined tissue distribution and accumulation of OP after single oral application of 50, 100, and 200 mg/kg, single intravenous injection of 1, 5 and 10 mg/kg or daily application of 50 mg/kg for 14 consecutive days. After single oral administration of 200 mg/kg, Cmax of 213 $\pm$ 123 ng/ml was reached within the first 1.3 hr (Tmax) in the plasma. AUC was calculated for 1,333$\pm$484 ngㆍhr/ml. The final elimination half-life of plasma was longer than that of urine, but urinary clearance was lower than oral. A very small fraction of OP (Fe < 0.0017%) was excreted in urine within 24 hr. These results indicated that the major excretion route of OP was not urine. The mean maximal tissue distribution of OP was obserbed at 6 hr after treatment and slowly decreased time-dependently. High OP concentrations were detected in fat at 24 hr. The OP in fat was slowly released with longer elimination half-life and lower clearance than that of other tissues. OP was not accumulated in the liver following single oral application but 14-day oral treatments resulted in two-fold accumulation. It was probably due to the saturation of detoxification pathways. On the other hand, the mRNA expression of cytochrome P450 isoforms except CYP2C11 was not affected by OP at any dose. The expression of CYP2C11 mRNA decreased in a dose-dependent manner. This result suggests that OP changes expression of the male-specific cytochrome P450 isoforms in rat liver, and these changes are closely related to the toxic and estrogenic effect of OP.

• Journal of Environmental Health Sciences
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• v.26 no.3
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• pp.11-17
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• 2000

There are among the most relevant toxic emissions from incinerators such as polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), dioxin-like polychlorinated biphenyls (PCBs). Induction of cytochrome P4501A1 catalyzed 7-ethoxyresorufin O-deethylase(EROD) activity in mammalian cell culture(EROD bioassay) is thought to be a selective and sensitive parameter used for the quantification of dioxin-like components. In this study, the toxic emissions from several school waste incinerators were evaluated by determination of CYPIA catalytic activity and cytotoxicity using cell culture microbioassay. The incinerator residue and soil samples were collected from the schools located in Kyunggi province from April to June 1999. The samples were extracted in a Soxhlet apparatus using toluene for 20 hours. In order to clean-up, concentrated crude extracts were applied to basic alumina column. The EROD activities of extracts in the H4IIE cells were from 1.91$\pm$0.32 ng-TEQ/g to 24.54$\pm$3.48 ng-TEQ/g of biochemical-TEQ value. In soil samples, CYP1A catalytic activity was 0.09~0.64 ng-TEQ/g. EROD bioassay, seems to be a useful short-term bioassay when information about the biological response of complex environmental samples is needed. Although further study is needed, these results indicate that the potent toxic emissions are produced from school waste semi-incinerators.