• Proceedings of the PSK Conference
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• 2002.10a
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• pp.194-199
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• 2002

Many oxidative metabolites of tetrahydrocannabinols (THCs), active components of marijuana, were pharmacologically active, and 11-hydroxy-THCs, 11-oxo-${\Delta}^8$-THC, 7-oxo-${\Delta}^8$-THC, 8$\beta$, 9$\beta$-epoxyhexahydrocannabinol (EHHC), 9$\alpha$, l0$\alpha$-EHHC and 3'-hydroxy-${\Delta}^9$-THC were more active than THC in pharmacological effects such as catalepsy, hypothermia and barbiturate synergism in mice. Cannabidiol (CBD), another major component, was biotransfomred to two novel metabolites, 6-hydroxymethyl-${\Delta}^9$-THC and 3-pentyl-6, 7, 7a, 8, 9, lla-hexahydro-I, 7-dihydroxy-7, 1O-dimethyldibenzo[b, d]oxepin (PHDO) through 8R, 9-epoxy-CBD and 85, 9-epoxy-CBD, respectively. Both metabolites exhibited some pharmacological effects comparable to d9 - THe. Cannabinol (CBN), the other major component, was mainly metabolized to ll-hydroxy-CBN by hepatic microsomes of animals including humans. The pharmacological effects of the metabolite were higher than those of CBN demonstrating that II-hydroxylation of CBN is metabolic activation pathway of the cannabinoid as is the case in THCs. Tolerance and reciprocal cross-tolerance developed to pharmacological effects d8 - THC and ll-hydroxy-d8-THC , and the magnitude of tolerance development produced by the metabolite was significantly higher than that by d8-THC. The results indicate that ll-hydroxy-d8-THC has an important role not only in the pharmacological effects but also its tolerance development of d8 - THe. THCs and their metabolites competed to the specific binding of CP-55, 940, an agonist of cannabinoid receptor, to synaptic membrane from bovine cerebral cortex. The Ki value of THCs and their metabolites were closely paralleled to their pharmacological effects in mice. A novel cytochrome P450 (cyp2c29) was purified and identified as a major enzyme responsible for the metabolic activation of d8-THC at the II-position in the mouse liver. cDNA of CYP2C29 was cloned from a mouse cDNA library and its sequence was determined. The oxidation mechanism of THC by cyp2c29 was proposed.

• The KIPS Transactions:PartB
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• v.10B no.3
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• pp.281-286
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• 2003

A large number of features are collected for problem solving in real life, but to utilize ail the features collected would be difficult. It is not so easy to collect of correct data about all features. In case it takes advantage of all collected data to learn, complicated learning model is created and good performance result can't get. Also exist interrelationships or hierarchical relations among the features. We can reduce feature's number analyzing relation among the features using heuristic knowledge or statistical method. Heuristic technique refers to learning through repetitive trial and errors and experience. Experts can approach to relevant problem domain through opinion collection process by experience. These properties can be utilized to reduce the number of feature used in learning. Experts generate a new feature (highly abstract) using raw data. This paper describes machine learning model that reduce the number of features used in learning using heuristic function and use abstracted feature by neural network's input value. We have applied this model to the win/lose prediction in pro-baseball games. The result shows the model mixing two techniques not only reduces the complexity of the neural network model but also significantly improves the classification accuracy than when neural network and heuristic model are used separately.

• YAKHAK HOEJI
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• v.53 no.5
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• pp.259-264
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• 2009

The present study was to investigate the effect of naringin, a flavonoid, on the pharmacokinetics of losartan in rats. Pharmacokinetic parameters of losartan in rats were determined after an oral administration of losartan (9 mg/kg) in the presence or absence of naringin (0.5, 2.5 and 10 mg/kg). The pharmacokinetic parameters of losartan were significantly altered by the presence of naringin compared with the control group (given losartan alone). Presence of naringin significantly (p<0.05, 2.5 mg/kg; p<0.01, 10 mg/kg) increased the area under the plasma concentration?time curve (AUC) of losartan by 43.7~63.0% and peak plasma concentration ($C_{max}$) of losartan by 31.7~45.5%. Consequently, the absolute bioavailability (AB) of losartan in the presence of naringin was 43.8~62.9%, which was enhanced significantly (p<0.05, p<0.01) compared to that in the oral control group (22.4%). The relative bioavailability (R.B.) of losartan increased by 1.44- to 1.63-fold in the presence of naringin. However, there was no significant change in the peak plasma concentration ($T_{max}$) and terminal half-life ($t_{1/2}$) of losartan in the presence of naringin. In conclusion, the presence of naringin significantly enhanced the oral bioavailability of losartan, implying that presence of naringin might be mainly effective to inhibit the cytochrome P450 (CYP)3A-mediated metabolism, resulting in reducing gastrointestinal and hepatic first-pass metabilism and Pglycoprotein (P-gp)-mediated efflux of losartan in small intestine. Concurrent use of naringin or naringin-containing dietary supplement with losartan should require close monitoring for potential drug interactions.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.20 no.1 s.32
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• pp.130-144
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• 2007

UV-irradiated skin shows acutely erythema, edema, pigmantation (sunbum) and chronically coarse wrinkling, roughness, dryness, laxity (photoaging). Jawoongo(紫雲膏, JW) is clinically useful external application and effective bum, sunburn, wound and symptom of dryness(燥症) in skin disease. In this experiment, we examined if JW could cure the UVB-mediated acute skin damages, inhibit UVB-mediated oxidative stress and inflammation of skin, and block the photoaging. In vivo test, we found that JW could effectively cure the UVB-mediated acute skin damages(erythema, edema, angiogenesis, hyperplasia, infiltration of lymphocytes) and inhibit expression of HSP70, CYP1A1 and p53. We also found that JW could repair destruction of collagen fiber and inhibit activation of MMP-9, and inhibit expression of $NF-{\kappa}B$ p65, iNOS, hyperplasia of keratynocyte. In vitro test, we found that JW could inhibit expression of IKK, iNOS mRNA, and production of NO. These findings shows that JW could cure the UVB-mediated acute skin damages, inhibit UVB-mediated oxidative stress and inflammation of skin, and block photoaging.

• Toxicological Research
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• v.23 no.3
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• pp.189-196
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• 2007

Cytochrome P450 (P450) enzymes are the major catalysts involved in the biotransformation of various drugs, pollutants, carcinogens, and many endogenous compounds. Most of chemical carcinogens are not active by themselves but they require metabolic activation. P450 isozymes playa pivotal role in the metabolic activation. The activation of arylamines and heterocyclic arylamines (HAAs) involves critical N-hydroxylation, usually by P450. CYP1A2 plays an important role in these reactions. Broad exposure to many of these compounds might cause carcinogenicity in animals and humans. On the other hand, P450s can be also involved in the bioactivation of other chemicals including alcohols, aflatoxin B1, acetaminophen, and trichloroethylene, both in humans and in experimental animals. Understanding the P450 metabolic activation of many chemicals is necessary to develop rational strategies for prevention of their toxicities in human health. An important part is the issues of extrapolation between species in predicting risks and variation of P450 enzyme activities in humans.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.6
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• pp.805-811
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• 2016

This study was conducted to investigate the protective effects of water extract from Crassostrea gigas (CGW) against ethanol-induced hepatic toxicity in rats. Seventy-two male Wistar rats (6-week-old) were divided into six groups of 12 animals each: control group (1 mL saline/d), ethanol-treated group, positive control group (ethanol+Hovenia dulcis Thunb extract), CGWL group (ethanol+low dosage of CGW), CGWM group (ethanol+medium dosage of CGW), and CGWH group (ethanol+high dosage of CGW). All groups except the control group received ethanol (40% ethanol 5 g/kg) orally. CGW administration with ethanol resulted in prevention of ethanol-induced hepatotoxicity by increasing levels of serum alanine aminotransferase and ${\gamma}-glutamyltransferase$. CGW supplementation significantly reduced formation of malonaldehyde and inhibited reduction of hepatic glutathione and peroxidase levels, as compared with the ethanol-administration group. Further, CGW suppressed expression of CYP2E1, which was elevated by ethanol administration. Consequently, our results indicate that Crassostrea gigas may exert hepatoprotective effects against alcohol-induced hepatocyte injury by intensifying the anti-oxidative defense system.

• Asian-Australasian Journal of Animal Sciences
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• v.27 no.12
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• pp.1695-1704
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• 2014

Maternal malnutrition during pregnancy may give rise to female offspring with disrupted ovary functions in adult age. Neonatal ovary development predisposes adult ovary function, yet the effect of maternal nutrition on the neonatal ovary has not been described. Therefore, here we show the impact of maternal protein restriction on the expression of folliculogenic and steroidogenic genes, their regulatory microRNAs and promoter DNA methylation in the ovary of neonatal piglets. Sows were fed either standard-protein (SP, 15% crude protein) or low-protein (LP, 7.5% crude protein) diets throughout gestation. Female piglets born to LP sows showed significantly decreased ovary weight relative to body weight (p<0.05) at birth, which was accompanied with an increased serum estradiol level (p<0.05). The LP piglets demonstrated higher ratio of bcl-2 associated X protein/B cell lymphoma/leukemia-2 mRNA (p<0.01), which was associated with up-regulated mRNA expression of bone morphogenic protein 4 (BMP4) (p<0.05) and proliferating cell nuclear antigen (PCNA) (p<0.05). The steroidogenic gene, cytochrome P450 aromatase (CYP19A1) was significantly down-regulated (p<0.05) in LP piglets. The alterations in ovarian gene expression were associated with a significant down-regulation of follicle-stimulating hormone receptor mRNA expression (p<0.05) in LP piglets. Moreover, three microRNAs, including miR-423-5p targeting both CYP19A1 and PCNA, miR-378 targeting CYP19A1 and miR-210 targeting BMP4, were significantly down-regulated (p<0.05) in the ovary of LP piglets. These results suggest that microRNAs are involved in mediating the effect of maternal protein restriction on ovarian function through regulating the expression of folliculogenic and steroidogenic genes in newborn piglets.

• Toxicological Research
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• v.34 no.2
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• pp.151-162
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• 2018

Anti-diabetes activity of Catharsius molossus (Ca, a type of dung beetle) glycosaminoglycan (G) was evaluated to reduce glucose, creatinine kinase, triglyceride and free fatty acid levels in db mice. Diabetic mice in six groups were administrated intraperitoneally: Db heterozygous (Normal), Db homozygous (CON), Heuchys sanguinea glycosaminoglycan (HEG, 5 mg/kg), dung beetle glycosaminoglycan (CaG, 5 mg/kg), bumblebee (Bombus ignitus) queen glycosaminoglycan (IQG, 5 mg/kg) and metformin (10 mg/kg), for 1 month. Biochemical analyses in the serum were evaluated to determine their anti-diabetic and anti-inflammatory actions in db mice after 1 month treatment with HEG, CaG or IQG treatments. Blood glucose level was decreased by treatment with CaG. CaG produced significant anti-diabetic actions by inhiting creatinine kinase and alkaline phosphatase levels. As diabetic parameters, serum glucose level, total cholesterol and triglyceride were significantly decreased in CaG5-treated group compared to the controls. Dung beetle glycosaminoglycan, compared to the control, could be a potential therapeutic agent with anti-diabetic activity in diabetic mice. CaG5-treated group, compared to the control, showed the up-regulation of 48 genes including mitochondrial yen coded tRNA lysine (mt-TK), cytochrome P450, family 8/2, subfamily b, polypeptide 1 (Cyp8b1), and down-regulation of 79 genes including S100 calcium binding protein A9 (S100a9) and immunoglobulin kappa chain complex (Igk), and 3-hydroxy-3-methylglutaryl-CoenzymeAsynthase1 (Hmgcs1). Moreover, mitochondrial thymidine kinase (mt-TK), was up-regulated, and calgranulin A (S100a9) were down-regulated by CaG5 treatment, indicating a potential therapeutic use for anti-diabetic agent.

• Journal of Nutrition and Health
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• v.50 no.3
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• pp.217-224
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• 2017

Purpose: Although it is well known thatmortality and morbidity due to cardiovascular diseases are higher in salt-sensitive subjects than in salt-resistant subjects, their underlying mechanisms related to obesity remain unclear. Here, we focused on salt-sensitive gene variants unrelated to monogenic obesity that interacted with sodium intake in humans. Methods: This review was written based on the modified $3^rd$ step of Khans' systematic review. Instead of the literature, subject genes were based on candidate genes screened from our preliminary Genome-Wide Association Study (GWAS). Finally, literature related to five genes strongly associated with salt sensitivity were analyzed to elucidate the mechanism of obesity. Results: Salt sensitivity is a measure of how blood pressure responds to salt intake, and people are either salt-sensitive or salt-resistant. Otherwise, dietary sodium restriction may not be beneficial for everyone since salt sensitivity may be associated with inherited susceptibility. According to our previous GWAS studies, 10 candidate genes and 11 single nucleotide polymorphisms (SNPs) associated with salt sensitivity were suggested, including angiotensin converting enzyme (ACE), ${\alpha}$-adducin1 (ADD1), angiotensinogen (AGT), cytochrome P450 family 11-subfamily ${\beta}$-2 ($CYP11{\beta}$-2), epithelial sodium channel (ENaC), G-protein b3 subunit (GNB3), G protein-coupled receptor kinases type 4 (GRK4 A142V, GRK4 A486V), $11{\beta}$-hydroxysteroid dehydrogenase type-2 (HSD $11{\beta}$-2), neural precursor cell-expressed developmentally down regulated 4 like (NEDD4L),and solute carrier family 12(sodium/chloride transporters)-member 3 (SLC 12A3). We found that polymorphisms of salt-sensitive genes such as ACE, $CYP11{\beta}$-2, GRK4, SLC12A3, and GNB3 may be positively associated with human obesity. Conclusion: Despite gender, ethnic, and age differences in genetics studies, hypertensive obese children and adults who are carriers of specific salt-sensitive genes are recommended to reduce their sodium intake. We believe that our findings can contribute to the prevention of early-onset of chronic diseases in obese children by facilitating personalized diet-management of obesity from childhood to adulthood.

• Korean Journal of Acupuncture
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• v.19 no.1
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• pp.7-13
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• 2002

The effects of Cnidium officinale Makino aqua-acupuncture solution (COMAS) and Cnidium officinale Makino water-extraced solution (COMWS) on the CYP1A1 activity and benzo[a]pyrene(B[a]P)-DNA adduct formation were examined. There were 6.8%, 12.1%, 15.1%, 18.3% and 22.6% inhibition in the activity of cytochrome 4501A1 enzyme with the treatment of $0.1{\times},\;0.5{\times},\;1{\times},\;3{\times},\;and\;5{\times}$ COMAS, respectively. At concentration of $0.1{\times}$ COMAS, the binding of $[^3H]B[a]P$ metabolites to DNA of NCTC-clone 1469 cell was significantly inhibited by 56.9%. These results suggest that COMAS has chemopreventive potential by inhibiting cytochrome P4501A1 activity and benzo[a]pyrene-DNA adduct formation.