• Journal of Life Science
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• v.21 no.11
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• pp.1558-1564
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• 2011

Cytochrome P450 2J2 (CYP2J2) plays important roles in the metabolism of endogenous metabolites such as arachidonic acid as well as therapeutic drugs. CYP2J2 is overexpressed in human cancer tissues and cancer cell lines, as well as in epoxyeicosatrienoic acids (EETs) and CYP2J2-mediated metabolites, and prevent apoptosis of cancer cells. This study aimed to screen marketed drugs for inhibitory potential on CYP2J2 isoforms using human liver microsomes. The initial screen isolated 4 compounds, from 120 marketed drugs, that inhibited the CYP2J2-mediated astemizole O-demethylation more than 50% in the following the order: haloperidol (75%) > terfenadine (56%) > aripiprazole (55%) > miconazole (52%). Miconazole strongly inhibited CYP2J2-mediated ebastine hydroxylation ($IC_{50}$=11.2 ${\mu}M$) and terfenadine hydroxylation ($IC_{50}$=2.2 ${\mu}M$), and terfenadine also inhibited CYP2J2-mediated ebastine hydroxylation ($IC_{50}$=13.6 ${\mu}M$) in a dose dependent manner. The present data suggest that these drugs are potential candidates for further evaluation for their anti-cancer activities.

• Journal of Korean Medicine Rehabilitation
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• v.25 no.2
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• pp.15-35
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• 2015

Objectives This study was performed to investigate the effects of Bujasasim-tang ethanol extract (BST) on oxidative stress, inflammation and osteoarthritic rat model. Methods To ensure safety of BST, heavy metal levels were measured and cytotoxicity test was done. In vitro, To evaluate antioxidative effects of BST, total phenolic contents, 1,1-diphenyl-2-picryl-hydrazyl (DPPH), 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) scavenging activity, reactive oxygen species (ROS) levels were measured. Also, to evaluate anti-inflammatory effects of BST treated group, total nitric oxide (NO) and pro-inflammatory cytokines (IL-$1{\beta}$, IL-6, TNF-${\alpha}$) levels were measured in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. In vivo, We injected MIA $50{\mu}l$ (60 mg/ml) into knee joints of rats to induce osteoarthritis. Rats were divided into total 3 groups (normal, control, BST treated group, each n=7). Normal group was not treated at all without inducing osteoarthritis and taken normal diet. Control group was induced osteoarthritis by MIA and taken with 2 ml of distilled water once a day for 4 weeks. BST treated group was induced osteoarthritis by MIA and taken BST 2 ml (200 mg/kg/mouse) once a day for 4 weeks. We evaluated dynamic weight bearing with the Incapacitance Test Meter. At the end of experiment, the rats were sacrificed to observe the functions of liver and kidney, changes of WBC, neutrophil, lymphocyte, monocyte levels in blood, to evaluate the levels of pro-inflammatory cytokines, tissue inhibitor of metallopreteinases-1 (TIMP-1), matrix metalloproteinase-9 (MMP-9), prostaglandin $E_2$ ($PGE_2$), leukotriene $B_4$ ($LTB_4$) within serum. We observed change of articular structures by Hematoxylin & Eosin (H&E), safranin-O staining method and measured amount of cartilage by micro CT-arthrography. Statistical analysis was done by unpaired student's t-test with significance level at p<0.05 in SPSS 11.0 for windows. Results 1. Safety of the BST was identified. 2. AST, ALT, BUN, creatinine levels of BST treated group were within normal limit. In vitro, 1. DPPH and ABTS free radical scavenging activities of BST showed dose-dependent increase. 2. ROS production were significantly decreased. 3. Total nitric oxide (NO) and IL-$1{\beta}$ production were decreased. 4. IL-6 and TNF-${\alpha}$ production were significantly decreased. In vivo, 1. Weight bearing ability was significantly increased. 2. WBC, neutrophil, lymphocyte, monocyte levels in blood were decreased. 3. IL-$1{\beta}$ and TNF-${\alpha}$ levels in serum were significantly decreased. and the IL-6 level was decreased. 4. TIMP-1, MMP-9, $LTB_4$, $PGE_2$ levels in serum were significantly decreased. 5. Cartilage volume of BST treated group was significantly increased. Also changes of cartilage, synovial membrane, fibrous tissue were suppressed. Conclusions The results obtained in this study Bujasasim-tang have effects of antioxidative, anti-inflammatory, relieve pain and protection of cartilage. Therefore we expect that Bujasasim-tang is effective treatment for osteoarthritis.

• Tuberculosis and Respiratory Diseases
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• v.53 no.2
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• pp.196-201
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• 2002

Malignant melanoma is a highly malignant form of cutaneous cancer derived from melanocytes. The lesion frequently metastasizes to the lymph nodes, lung, liver and bone. However, an endobronchial metastasis and a primary malignant. melanoma of the lung are quite rare. We report a case of an unknown primary malignant melanoma with a pulmonary and endobronchial metastasis in a 34 years old male. He complained of coughing and black-colored sputum. Abnormal skin and mucosal lesions were not found during a physical examination. A chest X-ray revealed multiple nodular masses in both lung fields. A flexible bronchoscopy showed two yellowish small nodules at the entry of left lower bronchus. Vimentin, the S-100 protein, and HMB-45 stain positive melanoma cells were detected at the bronchoscopic biopsy specimen.

• Tuberculosis and Respiratory Diseases
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• v.59 no.5
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• pp.551-555
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• 2005

Hemangiopericytoma is a rare neoplasm that originates from small peri-capillary spindle shaped cells called pericytes. The most common sites of origin are the thigh, the pelvis and the retroperitoneum. A primary pulmonary hemangiopericytoma is particularly unusual. However, more than 50% of hemangiopericytoma cases metastasize to the lungs, the bone, and the liver. A long-term clinical and radiological follow up is recommended due to the high risk of recurrence of a potential malignancy. We report a case of a metastatic hemangiopericytoma in the lung that had initially developed in the thigh of a 53 year-old woman 6 years ago. The authors emphasize the long-term follow-up of this type of rare sarcoma.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.16 no.3
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• pp.116-128
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• 2003

Objectives : The incidence of allergic rhinitis has increased but treatment in most cases has only dealt with the symptoms. Medicine has been developed that shows fewer side effects. However, some side effects and the psychological stress over taking medicine has remained. There have been no studies so far performed on the effect of this Jeulminmilmae-tang's use, only. The purpose of this study was find out the therapeutic effects of its exclusive use on an Animal Model with Allergic Rhinitis. Methods : Thirty Sprague-Dawley rats were divided into three group : normal group, control group and sample group. To induce the allergic rhinitis in control group and sample group, rats were sensitized intraperitoneally with 0.1$\%$ ovalumin solution 3 times at intervals of 1 week. Then intranasal sensitization was performed by diffusing 0.1$\%$ ovalumin solution 3 times at intervals of 2 days. After that time, rats in the sample group were oral administration treated by Jeulminmilmae-tang for 28 days. Compared with the sample group, rats in the control group were oral administration treated by normal saline for 28 days. We observed changes in nasal mucosa and submucosa; also changes in the segment of neutrophil, eosinophil, Iympocyte and monocyte in blood. We used the statistical methods of student t-test(p 〈0.05). And we observed the changes of AST, ALT of three groups and used anova test statistically. Results : The segment of eosinophil was significantly decreased in treated group when compared with the control group(p 〈0.05). The segment of neutrophil. in blood were decreased in the treated group when compared with the control group but. that was not significant statistically(p 〈0.05). There were some regrowth of the cilium in the treated group. Histologic changes showed edema congestion and expantion of grandular cells in nasal submucosa and hypertrophy of epithelium ill nasal mucosa were decreased in treated group when compared with control group. Effects of Jeulminmilmae-tang on the liver function were also studies in rats. Treatment of Jeulminmilmae-tang did not affected on AST and ALT. Conclusions : The results may suggest that oral administration treatment using Jeulminmilmae-tang decreases the inflammatory response on an Animal Model with Allergic Rhinitis.

• Journal of Ginseng Research
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• v.30 no.1
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• pp.41-48
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• 2006

In the browning reaction of Korean ginseng, it appears that enzymatic and non-enzymatic browning reaction occurred In initial stage of steaming fresh ginseng at low temperature, and then non-enzymatic browning reaction followed in the drying period after steaming. Browning reaction of red ginseng occurred between $60{\sim}90$ min of steaming at $100^{\circ}C$, and browning pigments of red ginseng were mostly water soluble substances. The structural characteristics of water soluble browning reaction products(WS-BRPs) isolated from Korean red ginseng were showed the presence of hydroxyl, amide carbonyl and aliphatic methane groups. From sugar analysis it was identified that L and S-1, melanoidins isolated from red ginseng, contained two kinds of sugars, glucose and xylose, and the other melanoidin S-2 contained the previous and fructose. In order to find out pertinent methods for the acceleration of browning during ginseng processing, various treatment were made on fresh ginseng with sugars, amino acids and inorganic nitrogenous compounds and the extent of browning was measured. Among sugar tested, maltose resulted in the greatest acceleration of browning followed in decreasing order by glucose and lactose, whereas pentoses, fructose, sucrose and raffinose had negligible effect. A marked browning occurred in ginseng treated with basic amino acids, while the extent of browning was not greatly increased when ginseng was treated with aliphatic amino acids, hydroxyl amino acids, or acidic amino acids. The brown color intensity gradually increased with an increase of glucose concentration far up to 0.5M. L, S-1, and S-2 were found to have an ability to donate hydrogen to DPPH, and also they had anti-oxidative activity in the experiments of hydrogen peroxide scavenging, inhibitory activity in the formation of MDA from linoleic acid, auto oxidation of ok-brain homogenates, lipid peroxidation by the enzymatic and non-enzymatic system in liver microsome fraction, and mitochondrial fraction etc. The amounts of acidic polysaccharide(AP) in red ginseng were higher than those of wild and cultured Panax quinquefolius, Panax notoginseng as well as white ginseng (Panax ginseng). In white ginseng, the AP amount is no difference in root ages or sizes, also, the AP amount of ginseng body was similar to that of rhizome, but was higher than that of leaf and epidermis. Addition of red ginseng acidic polysaccharide(RGAP) increased production of nitric oxide(NO) and tumor necrosis factor (TNF)-$\alpha$ in the rodent macrophage cultures, and treatment of RGAP in vivo stimulated tumoricidal activities of natural killer (NK) cells.

• Journal of Life Science
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• v.19 no.8
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• pp.1119-1124
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• 2009

Hyperlipidemia has been reported to be associated with the development of fatty liver. Palmitic acid, a major saturated fatty acid, is involved in the development of diverse diseases. The activation of mitogen activated protein kinases (MAPKs), such as Jun N-terminal kinase (INKs) and p38 MAPK is implicated in the apoptosis in diverse cells. Thus, this study was conducted to investigate the effects of palmitic acid on apoptosis and its relationship between JNK and p38 MAPK in cultured rat hepatocytes. In the present study, palmitic acid (>50 uM) decreased cell proliferation and increased lactate dehydrogenase activity in hepatocytes, which was blocked by the treatment of SP600125 (a JNK inhibitor) and SB203580 (a p38 MAPK inhibitor). Indeed, palmitic acid decreased Bcl-2 expression but increased Bax expression in rat hepatocytes, which was blocked by the treatment of SP600125 and SB203580. In addition, palmitic acid decreased glutathione (GSH) content and increased lipid peroxide formation, which was blocked by the treatment of SP600125 and SB203580. Western immunoblotting analysis also revealed that palmitic acid increased JNK and p38 MAPK. In conclusion, palmitic acid induced apoptosis through oxidative stress via JNK and p38 MAPK activation in rat hepatocytes.

• Journal of Life Science
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• v.18 no.3
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• pp.381-386
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• 2008

Deep sea water was tested for cancer chemopreventive activity by measuring the activities of ${\beta}-$ naphthoflavone $({\beta}-NF)-induced$ cytochrome P 450 1A2 (CYP 1A2), quinone reductase (QR) and glutathione-S-transferase (GST), glutathione (GSH) levels, and ornithine decarboxylase (ODC) activity. The in vitro incubation of rat liver microsome with deep sea water (a hardness range of $100{\sim}1,000$) showed a hardness-dependent inhibition of CYP 1A2 activity. QR and GST activities were induced about $1.1{\sim}1.2$ fold with the treatment of deep sea water in murine hepatoma Hepa 1clc7 cells. In addition GSH levels were increased $1.3{\sim}1.4$ fold in a hardness range of $100{\sim}1,000$. The deep sea water showed 20.3 and 35.0% inhibition of 12-O- tetradecanoylphorbol-13-a-cetate (TPA)-induced ODC activity at hardness 800 and 1,000, respectively. Therefore, deep sea water is worth further investigation with respect to cancer chemoprevention or therapy.

• Journal of Life Science
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• v.23 no.4
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• pp.529-536
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• 2013

This study was carried out to investigate the characteristics of white soybean Chungkookjang fermented by Bacillus subtilis D7. The highest germination rate was obtained under $25^{\circ}C$ when water was supplied for 4 days at intervals of 2 hr. The total isoflavone content was 971.3 ${\mu}g/g$ before germination and 1023.8 ${\mu}g/g$ after germination. The amino type- and ammonia type-nitrogen contents of Chungkookjang were proportional to the fermentation time. The pH values of all Chungkookjang soybeans increased up to pH 7.8-8.0 during fermentation. The number of viable cells in all Chungkookjang soybeans increased significantly up to 24 hr. The protease activity of all Chungkookjang soybeans increased up to 30-36 hr. The ${\alpha}$- and ${\beta}$-amylase activities of Chungkookjang fermented by B. subtilis D7 were enhanced with increasing fermentation time. Analysis of the effect of Chungkookjang intake on the liver function of mouse showed that the alkaline phosphatase (ALP) activity and the superoxide dismutase (SOD) activity in the Chungkookjang diet group were markedly higher than those in the control group. The asparatate aminotransferase (AST) activity in the germinated soybean Chungkookjang diet group was higher than that in the nongerminated soybean Chungkookjang diet group. Therefore, Chungkookjang soybeans fermented with B. subtilis D7 can be expected to have an increased content of functional components and improved quality characteristics.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.44 no.2
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• pp.141-148
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• 2011

This feeding experiment was conducted to investigate the effects of dietary inclusion of various additives on growth performance, hematological parameters, fatty acid composition, gene expression and histopathological changes in juvenile olive flounder (Paralichthys olivaceus). Eleven isonitrogenous (49% crude protein) and isolipidic (10% crude lipid) experimental diets were formulated: no additives (Con); 5% kelp meal (Ke); 10% krill meal (Kr); 1% garlic powder (Ga); 1% citrus meal (Ci); 3% onion powder (On); 1% ginger powder (Gi); 1% mugwort powder (Mu); 1% licorice powder (Li); 1% wasabi powder (Wa); and a mixture (Mix) of these additives. Three replicate groups of juvenile flounder (average weight of 8.5 g) were fed one of the experimental diets to visual satiety twice a day for 15 weeks. The dietary inclusion of additives did not affect survival, weight gain, specific growth rate feed efficiency, daily feed intake, daily protein intake, protein efficiency ratio, hepatosomatic index and visceralsomatic index of the fish. Plasma triglyceride levels were significantly lower in fish fed the Ke, Ga, On, Gi, Mu, Li, and Mix diets than in fish fed the control diet. Plasma glucose, glutamic oxaloacetic transaminase and total cholesterol did not differ among dietary treatments. No significant difference was observed in fatty acid composition and lipid content of the dorsal muscle in fish fed the experimental diets. Myosin gene expression did not differ significantly among treatments after 5 weeks but was significantly lower in fish fed the Kr, Ci, Li, and Mix diets than in control group after 15 weeks. Histopathological analysis showed mild gill hyperplasia and mild necrosis of liver parenchymal cells in several individuals of each experimental group. These conditions were also observed in the control group and were not thought to be related to the inclusion of feed additives. The present findings indicate that the dietary inclusion of additives did not affect growth performance, fatty acid composition, gene expression, and histopathological changes in juvenile flounder. However, plasma triglyceride content may be reduced by supplementation with 5% kelp meal, 3% onion powder, 1% garlic powder, 1% ginger powder, 1% mugwort powder, and the additive mixture.