Kim, Min Kyoung;Yun, Kwang Jun;Lim, Da Hae;Kim, Jinju;Jang, Young Pyo
Biomolecules & Therapeutics
/
v.24
no.6
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pp.630-637
/
2016
The chemical components and biological activity of Camellia mistletoe, Korthalsella japonica (Loranthaceae) are relatively unknown compared to other mistletoe species. Therefore, we investigated the phytochemical properties and biological activity of this parasitic plant to provide essential preliminary scientific evidence to support and encourage its further pharmaceutical research and development. The major plant components were chromatographically isolated using high-performance liquid chromatography and their structures were elucidated using tandem mass spectrometry and nuclear magnetic resonance anlysis. Furthermore, the anti-inflammatory activity of the 70% ethanol extract of K. japonica (KJ) and its isolated components was evaluated using a nitric oxide (NO) assay and western blot analysis for inducible NO synthase (iNOS) and cyclooxygenase (COX)-2. Three flavone di-C-glycosides, lucenin-2, vicenin-2, and stellarin-2 were identified as major components of KJ, for the first time. KJ significantly inhibited NO production and reduced iNOS and COX-2 expression in lipopolysaccharide-stimulated RAW 264.7 cells at $100{\mu}g/mL$ while similar activity were observed with isolated flavone C-glycosides. In conclusion, KJ has a simple secondary metabolite profiles including flavone di-C-glycosides as major components and has a strong potential for further research and development as a source of therapeutic anti-inflammatory agents.
Cigarette smoke (CS) induces oxidative and nitrosative stress to the respiratory tract (RT) via both oxidants contained in CS and by CS-induced activation of RT inflammatory-immune pro-oxidant processes. CS exposure has been associated with reduced levels of plasma micronutrient antioxidants, in part due to an increased utilization and turnover of alpha-tocopherol (AT). It has been suggested that gamma-tocopherol (GT) may have an expanded spectrum of antioxidant activation compared to alpha-tocopherol (AT). In order to investigate effects of high GT supplementation as compared to AT, C57 BL/6 mice were fed control AT (35 mg/kg diet) or high GT (1,000 mg/kg diet) diet for 8-10 weeks and then exposed to 60 $mg/m^3$ CS, 6 hr/day for 3 days. AT and GT levels and their metabolites were measured at endpoints. High GT supplementation significantly reduced AT levels in plasma, liver and lung compared to AT. CS increased levels of AT and GT in plasma and lung of control AT group but decreased GT levels in lung of high GT supplemented group. Moreover, CS significantly decreased GT metabolite, gamma-CEHC. The results suggest that high GT supplementation have selective modulation of concentrations of vitamin E and its metabolite in plasma and lung but not in liver against in vivo CS exposure.
Kim, Ah-Reum;Kim, Su-Na;Lee, Hyun-Gee;Jeon, Byeong-Bae;Park, Won-Seok
Journal of the Society of Cosmetic Scientists of Korea
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v.38
no.4
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pp.311-319
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2012
Seborrheic dermatitis (SD) is the skin disease occurred because of Malassezia yeast which grows on the skin and scalp, and this yeast lives on sebum lipid, and their metabolite, free lipid acids are thought to be the main irritant on skin. To find out effective cosmeceutical ingredients to treat SD symptoms, we established novel cell-based in vitro model mimicking SD symptoms. This in vitro model adopted the co-culture system with primary sebocyte & HaCaT keratinocyte. We used M. globosa yeast extract, arachidonic acid, linoleic acid and dihydrotestosterone as SD inducers. In the co-culture system with optimized concentrations for SD-inducing cocktail, the production of IL-8 and sebum lipids increased up to 2-fold, and then we screened with commercial essential oils by monitoring IL-8 as a key inflammatory biomarker. Then we found that Cinnamomum zeylanicum oil, Mentha arvensis oil effectively down-regulated IL-$1{\alpha}$, IL-6, IL-8 cytokines which over-produced by SD-inducing cocktail. Additionally, two essential oils also showed inhibitory effect on sebum lipid synthesis from primary sebocyte and growth inhibitory effect to M. globosa yeast (MICs were lower than 0.0625 %). Our recent results suggest that Cinnamomum zeylanicum oil and Mentha arvensis oil could be effective natural herbal remedies to relieve or protect scalp seborrheic dermatitis.
Methamphetamine (MA) is the most common and available drug of abuse in Korea and its primary metabolite is amphetamine (AP). Detection of AP derivatives, such as MA, AP, phentermine (PT), MDA, MDMA, and MDEA by the use of immunoassay screening is not reliable and accurate due to cross-reactivity and insufficient specificity/sensitivity. Therefore, the analytical process accepted by most urine drug-testing programs employs the two-step method with an initial screening test followed by a more specific confirmatory test if the specimen screens positive. In this study, a gas chromatography-mass spectrometric (GC-MS) method was developed and validated for confirmation of MA and AP in human urine. Urine sample (500 µL) was added with N-isopropylbenzylamine as internal standard and ethyl chloroformate as a derivatization reagent, and then extracted with 200 µL of ethyl acetate. Extracted samples were analysed with GC-MS in the SIM/ Scan mode, which were screened by Cobas c311 analyzer (Roche/Hitachi) to evaluate the efficiency as well as the compatibility of the GC-MS method. Qualitative method validation requirements for selectivity, limit of detection (LOD), precision, accuracy, and specificity/sensitivity were examined. These parameters were estimated on the basis of the most intense and characteristic ions in mass spectra of target compounds. Precision and accuracy were less than 5.2 % (RSD) and ±14.0 % (bias), respectively. The LODs were 3 ng/mL for MA and 1.5 ng/mL for AP. At the screening immunoassay had a sensitivity of 100% and a specificity of 95.1 % versus GC-MS for confirmatory testing. The applicability of the method was tested by the analysis of spiked urine and abusers' urine samples.
Kim, Yang-Ree;Kuh, Hyo-Jeong;Kim, Mi-Young;Kim, Yo-Sook;Chung, Woo-Chul;Kim, Sang-Il;Kang, Moon-Won
Archives of Pharmacal Research
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v.27
no.5
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pp.576-580
/
2004
Primaquine is used for relapses caused by vivax malaria hypnozoites. No studies on the pharmacokinetics of primaquine (PMQ) has been reported in Korean patients. In our study, thirty vivax malaria patients were given 15 mg primaquine daily for 14 days after 3 days of chloroquine treatment. Plasma samples were taken at intervals after each daily dose of PMQ for 3 days. Plasma concentrations of PMQ and carboxyprimaquine (CPMQ), the major metabolite of primaquine, were measured by HPLC. The PMQ concentrations reached a maximum of 0.28$\pm$0.18 $\mu\textrm{g}$/mL at 1.5 h after the first dose. The maximum concentration of CPMQ was 0.32$\pm$0.13 $\mu\textrm{g}$/mL at 4 h. Higher drug concentrations with repeated dosing were observed for CPMQ, but not for the parent drug, PMQ. The elimination half-life was 3.76$\pm$1.8 hand 15.7$\pm$12.2 h, for PMQ and CPMQ, respectively. Large variation in the plasma concentrations of both drugs was observed. Overall, PMQ is absorbed and metabolized rapidly after oral administration. It was noted that the mean peak plasma concentration of PMQ was significantly higher and that of CPMQ was lower in our patients compared to other studies. This suggests a potential difference of inter-ethnic groups, which warrants further investigations.
Kim, Se-Jin;Choi, Seungmok;Kim, Minsoo;Park, Changmin;Kim, Gyu-Lee;Lee, Si-On;Kang, Wonku;Rhee, Dong-Kwon
Journal of Ginseng Research
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v.42
no.3
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pp.370-378
/
2018
Background: Ginseng has been the subject of many experimental and clinical studies to uncover the diverse biological activities of its constituent compounds. It is a traditional medicine that has been used for its immunostimulatory, antithrombotic, antioxidative, anti-inflammatory, and anticancer effects. Ginseng may interact with concomitant medications and alter metabolism and/or drug transport, which may alter the known efficacy and safety of a drug; thus, the role of ginseng may be controversial when taken with other medications. Methods: We extensively assessed the effects of Korean Red Ginseng (KRG) in rats on the expression of enzymes responsible for drug metabolism [cytochrome p450 (CYP)] and transporters [multiple drug resistance (MDR) and organic anion transporter (OAT)] in vitro and on the pharmacokinetics of two probe drugs, midazolam and fexofenadine, after a 2-wk repeated administration of KRG at different doses. Results: The results showed that 30 mg/kg KRG significantly increased the expression level of CYP3A11 protein in the liver and 100 mg/kg KRG increased both the mRNA and protein expression of OAT1 in the kidney. Additionally, KRG significantly increased the mRNA and protein expression of OAT1, OAT3, and MDR1 in the liver. Although there were no significant changes in the metabolism of midazolam to its major metabolite, 1'-hydroxymidazolam, KRG significantly decreased the systemic exposure of fexofenadine in a dose-dependent manner. Conclusion: Because KRG is used as a health supplement, there is a risk of KRG overdose; thus, a clinical trial of high doses would be useful. The use of KRG in combination with P-glycoprotein substrate drugs should also be carefully monitored.
IARC classified areca quid as a human carcinogen. Areca quid chewed in Taiwan includes Piper betle inflorescence, which contains high concentrations of safrole (15 mg/fresh weight). Safrole is a documented rodent hepatocarcinogen, and chewing areca quid may contribute to human exposure (420 $\mu$m in saliva). The carcinogenicity of safrole is mediated through 1'-hydroxysafrole formation, followed by sulfonation to an unstable sulfate that reacts to form DNA adducts. Using human liver microsomes and Escherichia coli membranes expressing bicistronic human P450s, CYP2E1 and CYP2C9 were identified as the main P450s involved in the activation of safrole. We have demonstrated the presence of stable safrole-dGMP adducts in human oral tissues following areca quid chewing using $^{32}$ P-postlabeling and HPLC mass spectrometry methods. By studying 88 subjects with a known AQ chewing history and 161 matched controls, we have demonstrated that the presence of safrole-DNA adducts in peripheral blood cells was correlated to AQ chewing, and CYP2E1 seemed to play an important role in the modulation of safrole-DNA adduct formation. We have also shown that safrole can form stable safrole-DNA adducts as well as oxidative damages in rodent liver. However, the stable safrole-DNA adducts may represent a more significant initial lesion as compared to the rapidly repaired safrole-induced 8-hydroxy-2'-deoxyguanosine. This oxidative DNA damage is mediated through the formation of hydoryxchavicol, the major safrole metabolite in human urine. Hydroxychavicol may have gone through two-electron oxidation to the o-quinone; then via one-electron reduction to semiquinone radicals to generate oxidative DNA damage. However, these reactive metabolites can be efficiently conjugated by GSH. These data suggest that safrole may contribute to the initiation of oral carcinogenesis through safrole-DNA adduct and not oxidative DNA damage. In addition, CYP2E1 may modulate this adduct formation.
Three sheep fitted with cannulas in the rumen and the caecum were used in a $3{\times}3$ Latin square design to study the changes in ruminal and caecal microbial populations and their metabolite composition with ammoniated rice straw feeding. The 3 diets contained either 80% untreated rice straw (UTS) or ammoniated rice straw (ATS) and 20% formula feed. These were a control diet (C), a urea supplemented diet (U) containing urea at 1.1% and an ammoniated rice straw diet (AT). Data were analyzed by analysis of variance and means separated by the Student Neumann Kuel's multiple comparison. AT feeding increased ruminal bacterial counts, in particular cellulolytic bacterial counts (p < 0.05) which were 1.8, 2.4 and 7.0 (${\times}10^6/ml$ ruminal fluid) for C, U and AT, respectively. There was an increasing tendency (p < 0.10) in ruminal fungal population with U; values were 2.0, 5.2, 3.1 (${\times}10^3/ml$ ruminal fluid) for C, U and AT, respectively. Ruminal protozoa counts were not significantly (p > 0.05) altered with diets. Caecal total viable bacterial count with AT was about thrice the value with C. Total VFA concentration in the rumen was significantly increased (p < 0.025) (7.7 mmol/dl for C and 8.2 mmol/dl for AT) and correspondingly, pH lowered when AT was fed. Sheep on AT tended to produce less acetate and more butyrate in the rumen without significance (p > 0.05). Similar to the rumen, total VFA concentrations of 4.4, 3.8 and 5.2 mmol/dl were detected, respectively, for C, U and AT. Caecal ammonia-nitrogen concentrations were about six-fold of that in the rumen, though there were no differences (p > 0.05) among treatments.
Kim, Moo-Jin;Lee, Seung-Deok;Kim, Kyung-Ho;Byun, Hyuk;Kim, Kap-Sung
Journal of Acupuncture Research
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v.23
no.2
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pp.103-111
/
2006
Objectives : Deer antler Water Extract(DAE), prepared from the pilose antler of Cervus korean TEMMINCK var. mantchuricus Swinhoe (Nokyong), a traditional immuno-suppressive and immuno-activating Korean herbal-acupuncture, is thought to play an important role in human bone remodeling. Methods : To determine whether DAE can induce the differentiation of resting zone chondrocytes(RC) or not, confluent cell cultures were pretreated for 24, 36, 48, 72, and 120hrs with DAE. At the end of pretreatment, the media were replaced with new media containing $10^{-10}{\sim}10^{-8}M\;1,25-(OH)_2D_3$ and the cells incubated for an additional 24hrs. Results : This second treatment was chosen because prior studies had shown that only the more mature growth zone chondrocytes(GC) respond to this vitamin $D_3$ metabolite. The effect of DAE pretreatment on cell maturation was confirmed by measuring alkaline phosphatase (ALPase)-specific activity. Changes in matrix protein synthesis were examined by measuring collagen synthesis, as well as $^{35}SO_4$ incorporation into proteoglycans. When RC cells were pretreated for 120h with DAE, treatment with $1,25-(OH)_2D_3$ caused a dose-dependent increase in ALPase-specific activity and collagen synthesis, however, the proteoglycan production was not affected. RC cells pretreated with $1,25-(OH)_2D_3$ responded like RC cells that had not received any pretreatment. Conclusion : These results indicate that DAE directly regulates the maturation of RC chondrocytes into GC chondrocytes. Therefore it was indicated that DAE may play a significant role in regulating chondrocyte maturation during endochondral ossification.
Purpose: Muscle mitochondria play a key role in regulating fatty acid and glucose metabolism. Dysfunction of muscle mitochondria is associated with metabolic diseases such as obesity and type 2 diabetes. Isorhamnetin (ISOR), also known as 3-O-methylquercetin, a quercetin metabolite, is a naturally occurring flavonoid in many plants. This study evaluated the effects of ISOR on the regulation of the mitochondrial function of C2C12 muscle cells. Methods: C2C12 muscle cells were differentiated for 5 days, and then treated in various concentrations of ISOR. Cytotoxicity was determined by assessing cell viability using the water-soluble tetrazolium salt-8 assay principle at different concentrations of ISOR and time points. Levels of the mitochondrial DNA (mtDNA) content and gene expression were measured by quantitative real-time polymerase chain reaction. The citrate synthase (CS) activity was quantified by the enzymatic method. Results: ISOR at a concentration of 10 µM did not show any cytotoxic effects. ISOR increased the mtDNA copy number in a time- or dose-dependent manner. The messenger RNA levels of genes involved in mitochondrial function, such as peroxisome proliferator-activated receptor-γ coactivator-1α, and uncoupling protein 3 were significantly stimulated by the ISOR treatment. The CS activity was also significantly increased in a time- or dose-dependent manner. Conclusion: These results suggest that ISOR enhances the regulation of mitochondrial function, which was at least partially mediated via the stimulation of the mtDNA replication, mitochondrial gene expression, and CS activity in C2C12 muscle cells. Therefore, ISOR may be useful as a potential food ingredient to prevent metabolic diseases-associated muscle mitochondrial dysfunction.
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