• Asian-Australasian Journal of Animal Sciences
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• 제29권4호
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• pp.523-529
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• 2016

An isotope dilution method using $[U-^{13}C]glucose$ and $[1-^{13}C]leucine$ (Leu) was conducted to evaluate the effects of rice straw supplemented with urea and molasses (RSUM-diet) on plasma glucose and Leu turnover rates in sheep. Nitrogen (N) balance, rumen fermentation characteristics and blood metabolite concentrations were also determined. Four sheep were fed either mixed hay (MH-diet), or a RSUM-diet with a crossover design for two 21 days period. Feed allowance was computed on the basis of metabolizable energy at maintenance level. The isotope dilution method was performed as the primed-continuous infusion on day 21 of each dietary period. Nitrogen intake was lower (p = 0.01) for the RSUM-diet and N digestibility did not differ (p = 0.57) between diets. Concentrations of rumen total volatile fatty acids tended to be higher (p = 0.09) for the RSUM-diet than the MH-diet. Acetate concentration in the rumen did not differ (p = 0.38) between diets, whereas propionate concentration was higher (p = 0.01) for the RSUM-diet compared to the MH-diet. Turnover rates as well as concentrations of plasma glucose and Leu did not differ between diets. It can be concluded that kinetics of plasma glucose and Leu metabolism were comparable between the RSUM-diet and the MH-diet, and rumen fermentation characteristics were improved in sheep fed the RSUM-diet compared to the MH-diet.

• Archives of Pharmacal Research
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• 제27권2호
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• pp.265-272
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• 2004

The pharmacokinetics of CKD-732 (6-0-4-[dimethyl-aminoethoxy)cinnamoyl]-fumagillolㆍhemioxalate) was investigated in male SD rats and beagle dogs after bolus intravenous administration. The parent compound and metabolites obtained from in vitro and in vivo samples were determined by LC/MS. The main metabolite was isolated and identified as an N-oxide form of CKD-732 by NMR and LC/MS/MS. CKD-732 was metabolized into either M11 or others by rapid hydroxylation, demethylation, and hydrolysis. The blood level following the intravenous route declined in first-order kinetics with $T_{1}$2/$\beta$ values of 0.72-0.78 h for CKD-732 and 0.92-1.09 h for M11 in rats at a dose of 7.5-30 mg/kg. In dogs, $T_{1}$2/$\beta$ values of CKD-732 and M11 were 1.54 and 1.79 h, respectively. Moreover, AUC values increased dose dependently for CKD-732 and M11 in rats and dogs. The CLtot and Vdss did not change significantly with increasing dose, indicating linear pharmacokinetic patterns. The excretion patterns through the urine, bile, and feces were also examined in the animals. The total amount excreted in urine, bile, and feces was 2.13% for CKD-732 and 1.29% for M11 in rats, and 1.58% for CKD-732 and 2.28% for M11 in dogs.

• Journal of Ginseng Research
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• 제44권3호
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• pp.461-474
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• 2020

Background: Ginseng effectively reduces fatigue in both animal models and clinical trials. However, the mechanism of action is not completely understood, and its molecular targets remain largely unknown. Methods: By screening for proteins that interact with the primary components of ginseng (ginsenosides) in an affinity chromatography assay, we have identified muscle-type creatine kinase (CK-MM) as a potential target in skeletal muscle tissues. Results: Biolayer interferometry analysis showed that ginsenoside metabolites, instead of parent ginsenosides, had direct interaction with recombinant human CK-MM. Subsequently, 20(S)-protopanaxadiol (PPD), which is a ginsenoside metabolite and displayed the strongest interaction with CK-MM in the study, was selected as a representative to confirm direct binding and its biological importance. Biolayer interferometry kinetics analysis and isothermal titration calorimetry assay demonstrated that PPD specifically bound to human CK-MM. Moreover, the mutation of key amino acids predicted by molecular docking decreased the affinity between PPD and CK-MM. The direct binding activated CK-MM activity in vitro and in vivo, which increased the levels of tissue phosphocreatine and strengthened the function of the creatine kinase/phosphocreatine system in skeletal muscle, thus buffering cellular ATP, delaying exercise-induced lactate accumulation, and improving exercise performance in mice. Conclusion: Our results suggest a cellular target and an initiating molecular event by which ginseng reduces fatigue. All these findings indicate PPD as a small molecular activator of CK-MM, which can help in further developing better CK-MM activators based on the dammarane-type triterpenoid structure.

• 한국환경농학회지
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• 제33권4호
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• pp.290-297
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• 2014

토양 수분과 실험 조건에 따른 Clothianidin의 토양 중 분해 및 잔류 특성의 변화를 비교 평가하고자 동일 지역 논 및 밭포장에서 토양잔류성 실험을 수행하였다. 또한 동일포장에서 채취한 토양을 대상으로 실험실 조건에서 토양 및 수중 잔류성 실험을 병행하였다. 논 및 밭포장에는 Clothianidin 8% 수용성입제(SG)를 600L/10a(0.024kg a.i./10a) 수준으로 전면 살포하였고 실험실 조건에서는 Clothianidin 표준용액을 0.25 mg/kg 수준이 되도록 점적 처리한 후, 경시적으로 토양 중 Clothianidin 및 주요 분해산물 TZMU, TZNG, MNG, TMG, MAI의 잔류량 변화를 조사하였다. Clothianidin의 토양 중 소실 양상은 포장 및 실험실 조건 모두에서 다중 1차 감쇄반응의 경향을 현저히 나타내었다. 총 Clothianidin을 기준으로 한 토양 중 반감기는 포장조건의 논 및 밭토양에서 각각 6.7-16.1일 및 6.9-8.2일 범위였으며 실험실 조건에서는 각각 56.3일 및 19.6일로 산출되었다. 포장조건에서의 토양 중 주요 분해산물로는 논토양에서 TZNG, TMG, MAI와 밭토양에서 TZMU와 MAI가 검출되어 다소 상이한 경향을 나타내었으나, 실험실조건에서는 논 및 밭토양 모두에서 TMG와 MAI가 주요 분해산물로 확인되었다. 수중잔류성 시험에서 Clothianidin의 토양수 중 반감기는 4.8일이었으며, TZMU가 주요 분해 대사산물로 조사되었다. 분해산물의 잔류 수준은 TZNG와 TZMU의 경우 약제처리 초기에 빠른 속도로 생성되었다가 급격히 감소되었던 반면, TMG와 MAI의 경우에는 지속적인 수준을 유지하였다. 약제처리 24일 후 포장 및 실험실조건에서 모화합물은 각각 80% 및 50%이상이 분해되었으며 그 이후 총 Clothianidin 잔류량의 대부분은 분해산물에 의한 것으로 평가되었다.

• 대한의생명과학회지
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• 제11권4호
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• pp.509-515
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• 2005

This study was conducted to determine the kinetics of cyclohexane metabolites (the biomarker on cyclohexane exposure), the changes of hepatic cyclohexane metabolizing enzyme activities and the metabolites of cyclohexane in urine or serum. The rats were sacrificed at 2, 4, 8, 12 and 24 hr after administration of one dose of cyclohexane (1.56 g/kg body weight, i.p.). The metabolites of cyclohexane in urine were identified as cyclohexanol, cyclohexanone, trans-l,2-cyclohexanediol and 1,4-cyclohexanediol with cyclohexane metabolite being 124.00, 0.78, 23.28 and 2.75 (g/g of creatinine, $1\times10^{-3}$). Most of the cyclohexanol and trans-l,2-cyclohexanediol were determined to be in the form of $\beta-glucuronide$ conjugates, whereas cyclohexanone and 1 ,4-cyclohexanediol were found as free forms. In toxicokinetics of serum cyclohexane metabolites, cyclohexanol showed a rapid increase, reaching the plateau at 4 hr, after this time rapidly decreased throughout 24 hr. Changes of cyclohexanone also showed the similar pattern with cyclohexanol except somewhat lower concentration. Trans-l,2-cyclohexanediol, however, showed a gradual increase until 12 hr with the continued same levels throughout 24 hr. On the other hand, 1,4-cyclohexanediol was detected as trace levels at 4 and 12 hr, respectively. The administration of cyclohexane led to a significant increase of hepatic aniline hydroxylase activity from 2 to 8 hr. The activity of hepatic alcohol dehydrogenase showed a significant increase at 4 hr and then were recovered to the level of the control at 24 hr. On the other hand, there were no differences in liver weightlbody weight between the control and cyclohexane-treated animals. However, there were the changes of aniline hydroxylase and alcohol dehydrogenase activities on time-dependent pattern after cyclohexane treatment, which influence on the degree of cyclohexane metabolites both in blood and urine. These results suggest that differential determination of cyclohexane metabolites in urine and serum may be able to be as a biomarker of cyclohexane-exposure in the body. But in this fields further study is needed.

• 한국균학회지
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• 제13권4호
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• pp.203-212
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• 1985

전국 각지 토양으로 부터 채취한 토양균을 screening하여 ${\alpha}-amylase$를 저해하는 물질을 생성하는 균주인 Streptomyces DMC-72를 선발하였다. 이 균주가 생성하는 저해제를 acetone 침전 및 이온 교환 수지인 Amberlite IRC-50, Amberlite CG-50과 SP-Sephadex C-25를 이용하여 분리하였다. 이 물질은 ${\alpha}-amylase$ 뿐만아니라 다른 amylase와 기타 효소에 대해서도 억제작용을 나타내었다. 이 물질은 기질인 soluble starch의 가수분해에 대해서 non-competitive하게 저해작용을 보이주고 있으며 열 및 넓은 범위의 pH에서 안정한 물질이었다. 이 물질은 anthrone 시험과 IR spectrum에 의해서 oligosaccharide계 화합물임을 알 수 있었다.

• Journal of Animal Science and Technology
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• 제60권11호
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• pp.26.1-26.9
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• 2018

Background: This experiment aimed at assessing polyphenol-rich plant biomass to use in complete feed making for the feeding of ruminants. Methods: An in vitro ruminal evaluation of complete blocks (CFB) with (Acacia nilotica, Ziziphus nummularia leaves) and without (Vigna sinensis hay) polyphenol rich plant leaves was conducted by applying Menke's in vitro gas production (IVGP) technique. A total of six substrates, viz. three forages and three CFBs were subjected to in vitro ruminal fermentation in glass syringes to assess gas and methane production, substrate degradability, and rumen fermentation metabolites. Results: Total polyphenol content (g/Kg) was 163 in A. nilotica compared to 52.5 in Z. nummularia with a contrasting difference in tannin fractions, higher hydrolysable tannins (HT) in the former (140.1 vs 2.8) and higher condensed (CT) tannins in the later (28.3 vs 7.9). The potential gas production was lower with a higher lag phase (L) in CT containing Z. nummularia and the component feed block. A. nilotica alone and as a constituent of CFB produced higher total gas but with lower methane while the partitioning factor (PF) was higher in Z. nummularia and its CFB. Substrate digestibility (both DM and OM) was lower (P < 0.001) in Z. nummularia compared to other forages and CFBs. The fermentation metabolites showed a different pattern for forages and their CFBs. The forages showed higher TCA precipitable N and lower acetate: propionate ratio in Z. nummularia while the related trend was found in CFB with V. sinensis. Total volatile fatty acid concentration was higher (P < 0.001) in A. nilotica leaves than V. sinensis hay and Z. nummularia leaves. It has implication on widening the forage resources and providing opportunity to use forage biomass rich in polyphenolic constituents in judicious proportion for reducing methane and enhancing green livestock production. Conclusion: Above all, higher substrate degradability, propionate production, lower methanogenesis in CFB with A. nilotica leaves may be considered useful. Nevertheless, CFB with Z. nummularia also proved its usefulness with higher TCA precipitable N and PF. It has implication on widening the forage resources and providing opportunity to use polyphenol-rich forage biomass for reducing methane and enhancing green livestock production.

• Plant Breeding and Biotechnology
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• 제6권4호
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• pp.404-412
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• 2018

The influenza neuraminidase (NA, E.C. 3.2.1.18), an antiviral, has been the target of high pharmaceutical companies due to its essential role in viral replication cycle. Perilla frutescens (P. frutescens) is used in traditional Chinese medicine for various diseases, such as cold due to wind-cold, headache and cough. In this context, four major polyphenolic compounds including rosmarinic acid-3-O-glucoside (1), rosmarinic acid (2), luteolin (3), and apigenin (4) isolated from P. frutescens were evaluated for their inhibitory effect on recombinant virus H1N1 neuraminidase (rvH1N1 NA). Among the test compounds, rosmarinic acid and luteolin inhibited the rvH1N1 NA with an $IC_{50}$ of 46.7 and $8.4{\mu}M$, respectively. The inhibition kinetics analyzed by the Dixon plots indicated that rosmarinic acid and luteolin were noncompetitive inhibitors and that the inhibition constant, $K_I$, was established as 43.9 and $14.3{\mu}M$, respectively. In addition, 578 genetically diverse accessions and 39 cultivars of P. frutescens were analyzed using HPLC to characterize the diversity of polyphenolic composition and concentration. The individual and total compositions exhibited significant difference (P < 0.05), especially rosmarinic acid which was detected as the predominant metabolite in all accessions (58.8%) and cultivars (62.8%). Yeupsil and Sangback cultivars exhibited the highest rosmarinic acid ($3,393.5{\mu}g/g$) and luteolin ($383.3{\mu}g/g$) content respectively. YCPL177-2 with the high concentration ($889.8{\mu}g/g$) of luteolin may be used as a genetic resource for breeding elite cultivars.

• 한국임상수의학회지
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• 제18권3호
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• pp.195-200
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• 2001

한우에서 albendazole을 경구투여하였을 때의 albendazole의 생체내 대사 및 약물동태학적 특성을 밝히고자 하였다. 거의 모든 가축종에서 albendazole은 투여 후 신속하게 대사산물로 전환되기 때문에 albendazole 대사산물에 대한 분석법 확립이 albendazole의 생체내 거동을 파악하기 위하여 매우 긴요하다. 본 연구에서는 albendazole 및 그 대사산물인 albendazole sulfoxide(ABZSO)와 albendazole sulfone(ABZS $O_2$)을 LC/MS을 이용하여 높은 분석능을 획득할 수 있었다. Albendazole을 한우에 5 mg/kg을 경구토여하였을 때 모약인 albendazole은 첫 두 채혈시점인 0.5 h 1h에서만 측정되었을 뿐 그 이후에는 측정되지 않았다. 한편, ABZSO와 ABZS $O_2$은 첫 채혈 시점인 0.5h부터 측정되어 투여 후 각각 48h 및 72h까지 측정이 가능하였다. 두 대사산물의 초기 생성속도는 비슷하였다. 혈중최고농도 도달시간 ($T^{max}$)은 ABZSO가 12.00 h로서 ABZS $O_2$의 22.50$\pm$3.00h보다 빨랐으며 (p<0.005), ABZSO의 최고농도 ( $C_{max}$)는 0.96$\pm$0.15 $\mu\textrm{g}$/ml이었고 ABZS $O_2$의 그것을 1.05$\pm$0.05 $\mu\textrm{g}$/ml를 나타내었다. 소실반감기 ($t^$\frac{1}{2}$, ke/$)는 ABZSO는 4.14$\pm$0.30 h로 ABZS $O_2$의 6.95$\pm$0.36 h보다 빨랐으며 (p<0.005), MRT (mean residence time)는 각각 13.11$\pm$0.05 h와 21.60$\pm$1.99h로서 ABZS $O_2$가 생체내에 더욱 오래 머물렀다 (p<0.005). ABZSO는 AU $C_{0}$$\longrightarrow$$\infty$/는 ABZS $O_2$의 그것보다 작았다. 이러한 사실로 미루어보아 ABZ을 한우에 구충목적으로 투여할 때 구충활성을 가진 것으로 알려져 있는 ABZSO의 생체내 거동을 고려하여 용법용량을 설정하여야 할 것으로 사료된다.