• Journal of the Korea Academia-Industrial cooperation Society
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• v.12 no.9
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• pp.4038-4045
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• 2011

To investigate whitening Effects of Angelica dahurica Radix Ethanol Extract (ADEE), we used melan-a cell line, brown guinea pig, and HMB-45. We treated with ADEE of 6.25, 12.5, 25, and 50 ${\mu}g/m{\ell}$ concentration in order to evaluate the effect of ADEE on cell viability and on morphological observation of melan-a cells. Also we were induced the artificial tanning spots by 1,500 mJ/$cm^2$ of ultraviolet B radiation on the backs of brown guinea pigs (approximately 450~500g) and then the test agent of $30{\mu}{\ell}$ was applied on the spots twice a day, five days a week, for five weeks respectively. The visible whitening effect was evaluated once a week. At the end of the experiment, the animals were sacrificed under anesthetization. The artificial tanning spots were obtained by biopsy punch and stained with HMB-45 to observe the gp100 proteins which were melanosomes. Our results show that cell viability was not reduce at ADEE concentrations between 6.25 and 50 ${\mu}g/m{\ell}$, melanin synthesis and melanocyte dendricity were decreased in ADEE treated melan-a cells increasing ADEE concentration. In the gross observation, ADEE treated groups had lower pigmentation than the vehicle control groups. And in the histological observation, ADEE treated groups had lower melanocytes than the vehicle control groups. Also in the quantitative analysis of the gp100 proteins using image analysis software, ADEE treated groups had a significantly lower value (p<0.001) than the vehicle control group and this resultsagreed with the results of observation under microscope. From these results, weconcluded that ADEE had positive whitening effect.

• Journal of Pharmaceutical Investigation
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• v.37 no.5
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• pp.297-303
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• 2007

The purposes of this study were to clarify the involvement of P-glycoprotein (P-gp) in the efflux of levosulpiride in knockout mice that lack the mdr1a1b gene and to evaluate the relationship between the genetic polymorphisms in MDR1 gene (exon 21) and levosulpiride disposition in healthy Korean subjects. After oral administration ($10\;{\mu}g/g$) of levosulpiride to mdr1a/1b(-/-) and wild-type mice, plasma and brain samples were obtained at 45 min. We also investigated the genotype for MDR1 (exon 21) gene in humans using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. A single oral dose of 25 mg levosulpiride was administered to 58 healthy subjects, who were based on the MDR1 genotype for the G2677T SNP. Blood samples were taken up to 36 hr after dosing. The concentrations of levosulpiride in mouse plasma and brain were statistically significant difference between the two animal groups (P<0.05). In addition, the average brain-to-plasma concentration ratio (Kp) of levosulpiride was 3.4-fold (P<0.01) higher in the mdr1a/1b(-/-) mice compared with the wild-type mice. We also found that the values of $AUC_{0-{\infty}$, partial AUC ($AUC_{0-4h}$) and $C_{max}$ were significantly different between homozygous 2677TT subjects and the subjects with at least one wild-type allele (GG and GT subjects, P=0.012 for $AUC_{0-{\infty}$; P=0.008 for $AUC_{0-4h}$; P=0.038 for $C_{max}$). The results confirm that levosulpiride is a P-gp substrate in vivo, and clearly demonstrate the effect of SNP 2677G>T in exon 21 of the MDR1 gene on levosulpiride disposition.

• Biomolecules & Therapeutics
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• v.18 no.3
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• pp.343-349
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• 2010

This study was designed to investigate the effects of ticlopidine on the pharmacokinetics of carvedilol after oral or intravenous administration of carvedilol in rats. Carvedilol was administered orally (3 mg/kg) or intravenously (1 mg/kg) without or with oral administration of ticlopidine (4, 12 mg/kg) to rats. The effects of ticlopidine on P-glycoprotein (P-gp) and cytochrome P450 (CYP) 2C9 activity were also evaluated. Ticlopidine inhibited CYP2C9 activity in a concentration-dependent manner with 50% inhibition concentration ($IC_{50}$) of $25.2\;{\mu}M$. In addition, ticlopidine could not significantly enhance the cellular accumulation of rhodamine 123 in MCF-7/ADR cells overexpressing P-gp. Compared with the control group (given carvedilol alone), the area under the plasma concentration-time curve (AUC) was significantly (12 mg/kg, p<0.05) increased by 14-41%, and the peak concentration ($C_{max}$) was significantly (12 mg/kg, p<0.05) increased by 10.7-73.3% in the presence of ticlopidine after oral administration of carvedilol. Consequently, the relative bioavailability (R.B.) of carvedilol was increased by 1.14- to 1.41-fold and the absolute bioavailability (A.B.) of carvedilol in the presence of ticlopidine was increased by 36.2-38.5%. Compared to the i.v. control, ticlopidine could not significantly change the pharmacokinetic parameters of i.v. administered carvedilol. The enhanced oral bioavailability of carvedilol may result from inhibition of CYP2C9-mediated metabolism rather than P-gpmediated efflux of carvedilol in the intestinal and/or in liver and renal eliminatin of carvedilol by ticlopidine.

• Biomolecules & Therapeutics
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• v.19 no.4
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• pp.493-497
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• 2011

The aim of this study was to investigate the effect of amlodipine on the pharmacokinetics of warfarin after oral and intravenous administration of warfarin in rats. Warfarin was administered orally (0.2 mg/kg) or intravenously (0.05 mg/kg) without or with oral administration of amlodipine (0.1 or 0.4 mg/kg) in rats. The effect of amlodipine on the P-glycoprotein (P-gp) as well as cytochrome P450 (CYP) 3A4 activity was also evaluated. Amlodipine inhibited CYP3A4 enzyme activity with 50% inhibition concentration ($IC_{50}$) of 9.1 ${\mu}M$. Compared to those animals in the oral control group (warfarin without amlodipine), the area under the plasma concentration-time curve (AUC) of warfarin was significantly greater (0.1 mg/kg, p<0.05; 0.4 mg/kg, p<0.01) by 26.5-53.5%, and the peak plasma concentration ($C_{max}$) was significantly higher (0.4 mg/kg, p<0.05) by 26.2% after oral administration of warfarin with amlodipine, respectively. Consequently, the relative bioavailability of warfarin increased by 1.26- to 1.53-fold and the absolute bioavailability of warfarin with amlodipine was significantly greater by 61.7-72.5% compared to that in the control group (47.4%). In contrast, amlodipine had no effect on any pharmacokinetic parameters of warfarin given intravenously. Therefore, the enhanced oral bioavailability of warfarin may be due to inhibition of CYP 3A4-mediated metabolism in the intestine and/or liver rather than renal elimination and P-gp by amlodipine.

• Asian-Australasian Journal of Animal Sciences
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• v.28 no.2
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• pp.188-199
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• 2015

Nineteen tanniferous browse plants were collected from South Africa to investigate their digestibility, gas production (GP) characteristics and methane production. Fresh samples were collected, dried in forced oven, and ground and analyzed for nutrient composition. In vitro GP and in vitro organic matter digestibility (IVOMD) were determined using rumen fluid collected, strained and anaerobically prepared. A semi-automated system was used to measure GP by incubating the sample in a shaking incubator at $39^{\circ}C$. There was significant (p<0.05) variation in chemical composition of studied browses. Crude protein (CP) content of the species ranged from 86.9 to 305.0 g/kg dry matter (DM). The neutral detergent fiber (NDF) ranged from 292.8 to 517.5 g/kg DM while acid detergent fiber (ADF) ranged from 273.3 to 495.1 g/kg DM. The ash, ether extract, non-fibrous carbohydrate, neutral detergent insoluble nitrogen, and acid detergent insoluble nitrogen and CP were negatively correlated with methane production. Methane production was positively correlated with NDF, ADF, cellulose and hemi-cellulose. Tannin decreased GP, IVOMD, total volatile fatty acid and methane production. The observed low methanogenic potential and substantial ammonia generation of some of the browses might be potentially useful as rumen manipulating agents. However, a systematic evaluation is needed to determine optimum levels of supplementation in a mixed diet in order to attain a maximal depressing effect on enteric $CH_4$ production with a minimal detrimental effect on rumen fermentation of poor quality roughage based diet.

• Animal Bioscience
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• v.35 no.9
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• pp.1379-1389
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• 2022

Objective: This study identified the major lactic acid bacteria (LAB) strains from different fermented total mixed rations (FTMRs) via metataxonomic analysis and evaluated the ability of their standard strain as ensiling inoculants for corn stover silage. Methods: The bacterial composition of eight FTMRs were analyzed by 16S rDNA sequencing. Corn stover was ensiled without LAB inoculation (control) or with 1×10⁶ cfu/g LAB standard strain (Lactobacillus vaginalis, Lactobacillus reuteri, Lactobacillus helveticus, or Lactobacillus paralimentarius) selected from the FTMRs or 10 g/t commercial silage inoculant (CSI) around 25℃ for 56 days. For each inoculation, a portion of the silage was sampled to analyze ensiling characteristics at time intervals of 0, 1, 3, 7, 14, 28, and 56 days, gas production (GP), microbial crude protein and volatile fatty acids as the measurements of rumen fermentation characteristics were evaluated in vitro with the silages of 56 days after 72 h incubation. Results: Lactobacillus covered >85% relative abundance of all FTMRs, in which L. pontis, L. vaginalis, L. reuteri, L. helveticus, and L. paralimentarius showed >4% in specific FTMRs. CSI, L. helveticus, and L. paralimentarius accelerated the decline of silage pH. Silage inoculated with L. paralimentarius and CSI produced more lactic acid the early 14 days. Silage inoculated with L. paralimentarius produced less acetic acid and butyric acid. For the in vitro rumen fermentation, silage inoculated with CSI produced more potential GP, isobutyric acid, and isovaleric acid; silage inoculated with L. helveticus produced more potential GP and isovaleric acid, silage inoculated with L. paralimentarius or L. reuteri produced more potential GP only. Conclusion: The standard strain L. paralimentarius (DSM 13238) is a promising ensiling inoculant for corn stover silage. The findings provide clues on strategies to select LAB to improve the quality of silage.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.2
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• pp.109-115
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• 2005

Endothelial activation and subsequent recruitment of inflammatory cells are important steps in atherogenesis. The increased levels of cell adhesion molecules (CAM) have been identified in diabetic vasculatures, but the underlying mechanisms remain unclear. To determine the relationship among vascular production of superoxide, expression of CAM and diabetes, superoxide generation and expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E- and P-selectin in the aorta from control (C57BL/6J) and diabetic mice (ob/ob) were measured. In situ staining for superoxide using dihydroethidium showed an increased superoxide production in diabetic aorta, accompanied with an enhanced NAD(P)H oxidase activity. Immunohistochemical analysis revealed that the endothelial expression of ICAM-1 ($3.5{\pm}0.4$) and VCAM-1 ($3.8{\pm}0.3$) in diabetic aorta was significantly higher than those in control aorta ($0.9{\pm}0.5$ and $1.6{\pm}0.3$, respectively), accompanied with the enhanced expression of gp91phox, a membrane subunit of NAD(P)H oixdase. Furthermore, there was a strong positive correlation (r=0.89, P＜0.01 in ICAM-1 and r=0.88, P＜0.01 in VCAM-1) between ICAM-1/VCAM-1 expression and vascular production of superoxide. The present data indicate that the increased production of superoxide via NAD(P)H oxidase may explain the enhanced expression of CAM in diabetic vasculatures.

• 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.

• Korean Journal of Agricultural Science
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• v.48 no.1
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• pp.73-81
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• 2021

The current study investigated how Saccharomyces cerevisiae ameliorates the adverse effects of aflatoxin on in vitro rumen fermentation. In this study, five groups (T₁: Control [basal feed]; T₂: T₁ + 300 ppb aflatoxin B1 [AFB₁] and T₃, T₄, and T₅: T₂ with 0.05, 0.1, and 0.2% of S. cerevisiae, respectively) were prepared and incubated in vitro. The results revealed that truly degradable dry matter (TDDM), gas production (GP), microbial biomass production (MBP), truly degradable organic matter (TDOM), partitioning factor (PF), total volatile fatty acids (TVFA), acetate (A), propionate (P) and butyrate (B) values in the control group (T₁) were higher (p < 0.05) than those of the AFB₁ fed group (T₂). The A : P ratio in the control group (T₁) was reduced (p < 0.05) when compared to that of the T₂ group. The TDDM, TDOM, GP, TVFA, A, P, and B values of T₃, T₄, and T₅ improved with the increasing levels of S. cerevisiae; however, the values of group T₅ were lower (p < 0.05) than that of the control. The values of MBP, A : P ratio and PF in group T₅ were statistically similar to that of the control. It was concluded that the inclusion of S. cerevisiae (0.05 to 0.20%) to the AFB₁ (300 ppb) contaminated feed partially to completely ameliorated the adverse effects of AFB₁ on the in vitro rumen fermentation parameters.

• Asian-Australasian Journal of Animal Sciences
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• v.24 no.1
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• pp.56-64
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• 2011

This study was conducted to evaluate the use of exogenous enzymes as a potential means of improving the ruminal digestion (i.e., degradability) of alfalfa hay and rice straw. Twenty six enzyme-additives were examined in terms of protein concentration and enzymic activities on model substrates. The exogenous enzymes contained ranges of endoglucanase, xylanase, ${\beta}$-glucanase, ${\alpha}$-amylase, and protease activities. Six of the enzyme additives were chosen for further investigation. The enzyme additives and a control without enzyme were applied to mature quality alfalfa hay substrate and subsequently incubated in rumen batch cultures. Five of the enzyme additives (CE2, CE13, CE14, CE19, and CE24) increased total gas production (GP) at 48 h of incubation compared to the control (p<0.05). The two additives (CE14 and CE24) having the greatest positive effects on alfalfa hay dry matter, neutral detergent fibre (NDF) and acid detergent fibre (ADF) degradability were further characterized for their ability to enhance degradation of low quality forages. The treatments CE14, CE24, a 50:50 combination of CE14 and CE24 (CE14+24), and control (no enzyme) were applied to mature alfalfa hay and rice straw. For alfalfa hay, application of the two enzyme additives, alone and in combination, increased GP compared to the control at 48 h fermentation (p<0.05), whereas only CE14 and CE14+24 treatments improved GP from rice straw (p<0.05). Rumen fluid volatile fatty acid concentrations throughout the incubation of rice straw were analyzed. Acetate concentration was slightly lower (p<0.05) for CE14${\times}$CE24 compared to the control, although individually, CE14 and CE24 acetate concentrations were not different from the control. Increases (p<0.05) in alfalfa hay NDF degradability measured at 12 and 48 h of incubation occurred only for CE14 (at 12 h) and for CE14+24 (at 12 and 48 h). Similarly, ADF degradability increased (p<0.05) with CE14 and CE14+24. As for rice straw, increased DM degradability was observed at 12 and 48 h of incubation for all enzyme treatments with an exception for CE14 at 12 h. The degradability of NDF was improved by all the enzyme treatments at either incubation time, while ADF degradability was only enhanced at 48 h. Overall, the enzymes led to enhanced digestion of mature alfalfa and there was evidence of improved digestibility of rice straw, an even lower quality forage.