• Biomolecules & Therapeutics
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• 제19권3호
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• pp.364-370
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• 2011

The purpose of this study was to investigate the effects of curcumin on the pharmacokinetics of loratadine in rats. The effect of curcumin on P-glycoprotein (P-gp) and cytochrome P450 (CYP) 3A4 activity was evaluated. Pharmacokinetic parameters of loratadine were also determined after oral and intravenous administration in the presence or absence of curcumin. Curcumin inhibited CYP3A4 activity with an IC50 value of 2.71 ${\mu}M$ and the relative cellular uptake of rhodamine-123 was comparable. Compared to the oral control group, curcumin significantly increased the area under the plasma concentration-time curve and the peak plasma concentration by 39.4-66.7% and 34.2-61.5%. Curcumin also significantly increased the absolute bioavailability of loratadine by 40.0-66.1% compared to the oral control group. Consequently, the relative bioavailability of loratadine was increased by 1.39- to 1.67-fold. In contrast, curcumin had no effect on any pharmacokinetic parameters of loratadine given intravenously, implying that the enhanced oral bioavailability may be mainly due to increased intestinal absorption caused via P-gp and CYP3A4 inhibition by curcumin rather than to reduced renal and hepatic elimination of loratadine. Curcumin enhanced the oral bioavailability of loratadine in this study. The enhanced bioavailability of loratadine might be mainly attributed to enhanced absorption in the gastrointestinal tract via the inhibition of P-gp and reduced fi rst-pass metabolism of loratadine via the inhibition of the CYP3A subfamily in the small intestine and/or in the liver by curcumin.

• 생약학회지
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• 제38권3호통권150호
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• pp.245-253
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• 2007

Artemisia princeps PAMPANINI has been used in traditional medicine of the treatment of inflammatory, liver dysfunction and order disorder in the far east countries including Korea. The present study was carried out to investigate the hepatoprotective effects of ethanol extract of Artemisia princeps (AP) and its fermented agents (AP-F) by lactic acid bacteria derived from human intestinal bacteria on liver injured rat induced by $CCl_4$ and d-galactosamine. Hepatoprotective activity was monitored by estimating serum ALT, AST, ALP, LDH, superoxide dismutase (SOD), glutathione redeuctase (GR) and glutathione peroxidase (Gpx) activities in the liver injured by hepatotoxin. Pretreating rats with AP or AP-F at the same dosage regimen significantly suppressed the acute elevation of serum transaminase, ALP, LDH and GR activities, and significantly increased the lowering of blood SOD and GR activites induced by hepatoxin. Based on these findings, it is presumed that AP and APF may have the hepatoprotective effect on $CCl_4$ and d-galactosamine-induced hepatotoxicity rat.

• Nutrition Research and Practice
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• 제6권1호
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• pp.16-20
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• 2012

The effects of retrograded rice on body weight gain, gut functions, and hypolipidemic actions in rats were examined. When the retrograded rice was produced by repetitive heating and cooling cycles, it contained significantly higher amounts of resistant starch ($13.9{\pm}0.98%$) than is found in common rice ($9.1{\pm}1.02%$) (P < 0.05). Sprague-Dawley rats were fed either common rice powder or retrograded rice powder, and mean body weight gain was significantly lower in the retrograded rice group (P < 0.05). The liver weight of the retrograded rice group ($14.5{\pm}0.5\;g$) was significantly lower than that of the common rice group ($17.1{\pm}0.3\;g$, P < 0.05). However, the weights of other organs, such as the kidney, spleen, thymus, and epididymal fat pad were not significantly affected by rice feeding. Intestinal transit time tended to be lower in rats fed retrograded rice when compared to rats fed the common rice, but the difference was not significant. The retrograded rice diet significantly increased stool output when compared to that in the common rice powder diet (P < 0.05), whereas fecal moisture content (%) was significantly higher in the retrograded rice group ($23.3{\pm}1.2$) than that in the common rice group ($19.1{\pm}1.2$) (P < 0.05). The retrograded rice group had significantly lower plasma cholesterol (P < 0.05), liver cholesterol (P < 0.05), and triacylglycerol contents in adipose tissue (P < 0.05) when compared to those in the common rice group. In conclusion, retrograded rice had higher resistant starch levels compared with those of common rice powder, and it lowered body weight gain and improved lipid profiles and gut function in rats.

• Journal of Microbiology and Biotechnology
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• 제12권1호
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• pp.8-13
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• 2002

The isoflavone glycosides are hydrolyzed by ${\beta}$-glucosidase from gut microbes to the bioactive aglycones. However, the specific bacteria from the human intestinal tract that are involved in the metabolism of these compounds are not known. This study was undertaken to develop a fermented soymilk which converts isoflavones to the more bioactive aglycones form using a Bifidobacterium strain. The ${\beta}$-glucosidase activity of 15 Bifidobacterium strains were measured during cell growth. Among them, Bifidobacterium sp. Int-57 was selected for this study, because it has the highest ${\beta}$-glucosidase activity. Growth, acid development, ${\beta}$-glucosidase activity, and the hydrolysis of daidzin and genistin were investigated in four soymilks inoculated with Bifidobacterium sp. Int-57. After 12 h of fermentation, the counts of viable Bifidobacterium sp. Int-57 in all the soymilks reached a level of more than $10^8$ cfu/ml, which was then maintained. The pH of soymilks started to decrease rapidly after 6 h of fermentation and leveled off after 18 h. The titratable acidity of BL# 1 soymilk, BL#2 soymilk, and JP#l soymilk increased from 0.18 to 1.21, 1.15, and $1.08\%$ over the fermentation period, respectively. After 24 h of fermentation, the $\beta$-glucosidase activity in BL#1 soymilk, BL#2 soymilk, JP#l soymilk, and JP#2 soymilk increased to 59.528, 40.643, 70.844, and 56.962 mU/ml, respectively. The isoflavone glycosides, daidzin and genistin, in soymilks were hydrolyzed completely in the relatively short fermentation time of 18 h. These results show that Bifidobacterium sp. Int-57 can be used as a potential starter culture for developing fermented soymilk which has completely hydrolyzed isoflavone glycosides.

• BMB Reports
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• 제48권9호
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• pp.513-518
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• 2015

Factors that modulate cholesterol levels have major impacts on cardiovascular disease. Niemann-Pick C1-like 1 (NPC1L1) functions as a sterol transporter mediating intestinal cholesterol absorption and counter-balancing hepatobiliary cholesterol excretion. The liver receptor homolog 1 (LRH-1) had been shown to regulate genes involved in hepatic lipid metabolism and reverse cholesterol transport. To study whether human NPC1L1 gene is regulated transcriptionally by LRH-1, we have analyzed evolutionary conserved regions (ECRs) in HepG2 cells. One ECR was found to be responsive to the LRH-1. Through deletion studies, LRH-1 response element was identified and the binding of LRH-1 was demonstrated by EMSA and ChIP assays. When SREBP2, one of several transcription factors which had been shown to regulate NPC1L1 gene, was co-expressed with LRH-1, synergistic transcriptional activation resulted. In conclusion, we have identified LRH-1 response elements in NPC1L1 gene and propose that LRH-1 and SREBP may play important roles in regulating NPC1L1 gene. [BMB Reports 2015; 48(9): 513-518]

• Asian-Australasian Journal of Animal Sciences
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• 제31권1호
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• pp.86-90
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• 2018

Objective: This study was conducted to investigate the effects of dietary detoxified Rhus verniciflua sap (RVS) on production performance, egg quality, lipid fractions of egg yolk, liver and serum, and the profile of cecal microflora in laying hens. Methods: Two hundred 52-week-old Hy-Line Brown layers were randomly divided into 4 groups with 5 replicates per group (2 hens per cage, 5 cages per replicate) and were provided with one of 4 experimental diets containing 0%, 0.05%, 0.1%, or 0.2% RVS, for 6 weeks. Due to unequal intervals of RVS doses, the interactive matrix language procedure of the SAS program was used to correct the contrast coefficients of orthogonal polynomials. Results: There were no differences in feed intake and egg weight among the groups. Egg production increased (linearly and quadratically, p<0.05) with increasing levels of RVS. Eggshell thickness increased (linear, p<0.05) as the level of RVS in diets increased. The levels of blood cholesterol and activities of glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase were not altered by dietary treatments. Increasing level of RVS increased (linear, p<0.05) the populations of cecal lactic acid bacteria. The content of yolk cholesterol decreased (linear, p<0.05) with increasing levels of dietary RVS, although there were no significant differences in each lipid fraction of the liver. Conclusion: This study indicates that dietary RVS could improve laying performance and eggshell quality, and affect cecal lactic acid bacteria in a dose-dependent manner.

• Journal of Pharmaceutical Investigation
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• 제40권5호
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• pp.291-296
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• 2010

This study was to investigate the effect of baicalein, an antioxidant, on the bioavailability of nicardipine after orally or intravenously administered nicardipine in rats. Nicardipine was administered orally (12 mg/kg) or intravenously (4 mg/kg) with or without orally administered baicalein (0.4, 2 or 10 mg/kg) to rats. In the inhibitory effect of baicalein on CYP3A4 activity, baicalein inhibited CYP3A4 activity with $IC_{50}$ values of 9.2 ${\mu}M$. The cell-based P-gp activity test using rhodamine-123 also showed that baicalein (30-10 ${\mu}M$, p<0.01) significantly inhibited P-gp activity. Compared with the control group (given nicardipine alone), the area under the plasma concentration-time curve (AUC) was significantly (2 mg/kg, P<0.05; 10 mg/kg, P<0.01) increased by 25.9-60.0%, and the peak concentration ($C_{max}$) was significantly (10 mg/kg, P<0.01) increased by 40.0% in the presence of baicalein after orally administration of nicardipine. Consequently, the relative bioavailability (R.B.) of nicardipine was increased by 1.26- to 1.60-fold and the absolute bioavailability (A.B.) was significantly (2 mg/kg, P<0.05; 10 mg/kg, P<0.01) increased by 26.0-59.9%. Compared to the i.v. control, baicalein did not significantly change pharmacokinetic parameters of nicardipine in i.v. administration. Accordingly, the enhanced oral bioavailability of nicardipine might be mainly due to increased intestinal absorption caused by P-gp inhibition rather than to reduced elimination of nicardipine by baicalein. The increase in the oral bioavailability might be mainly attributed to enhanced absorption in the small intestine via the inhibition of P-gp and reduced first-pass metabolism of nicardipine via the inhibition of the CYP3A subfamily in the small intestine and/or in the liver by baicalein. Based on these results, nicardipine dosage should be adjusted when given concomitantly with baicalein.

• 한국식품과학회지
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• 제3권3호
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• pp.151-162
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• 1971

가장 대중적(大衆的)으로 이용(利用)되고 있는 식품(食品)인 라면, 식빵 건조인절미를 쥐의 기초사료(基礎飼料)와 여러 가지로 혼합(混合)하여 10개군(個群)의 쥐에 대(對)해 사육(飼育)실험하여 생리적(生理的) 변화(變化)를 조사(調査)한 바 다음과 같았다. 1. 체중증가율(體重增加率)은 라면과 기초사료를 1 : 4 또는 1 : 2로 혼합(混合)한 경우가 가장 우수(優秀)하였으며 대조구(對照區)를 능가하였고 라면, 식빵, 인절미 등을 단용(單用)한 경우는 약간 저조(低調)하였다. 2. 사육시험중(飼育試驗中)의 장내세균(腸內細菌) flora의 변동(變動), 간기능(肝機能) 그리고 신장(腎臟)의 기능(機能)은 모두 정상적(正常的)이었으나, albumin globulin의 비율(比率)은 전(全) 시험구(試驗區)에서 대조구(對照區)와 공(共)히 약간 낮은 치(値)를 보였다. 3. 간(肝), 신장(腎臟)의 조직도 전시험구(全試驗區)에서 대조구(對照區)와 공(共)히 전시험기간중(全試驗其間中) 이상(異常)이 없었다.

• Journal of Microbiology and Biotechnology
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• 제22권6호
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• pp.838-848
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• 2012

Orally administered herbal glycosides are metabolized to their hydrophobic compounds by intestinal microflora in the intestine of animals and human, not liver enzymes, and absorbed from the intestine to the blood. Of these metabolites, some, such as quercetin and kaempherol, are mutagenic. The fecal bacterial enzyme fraction (fecalase) of human or animals has been used for measuring the mutagenicity of dietary glycosides. However, the fecalase activity between individuals is significantly different and its preparation is laborious and odious. Therefore, we developed a fecal microbial enzyme mix (FM) usable in the Ames test to remediate the fluctuated reaction system activating natural glycosides to mutagens. We selected, cultured, and mixed 4 bacteria highly producing glycosidase activities based on a cell-free extract of feces (fecalase) from 100 healthy Korean volunteers. When the mutagenicities of rutin and methanol extract of the flos of Sophora japonica L. (SFME), of which the major constituent is rutin, towards Salmonella typhimurium strains TA 98, 100, 102, 1,535, and 1,537 were tested using FM and/or S9 mix, these agents were potently mutagenic. These mutagenicities using FM were not significantly different compared with those using Korean fecalase. SFME and rutin were potently mutagenic in the test when these were treated with fecalase or FM in the presence of S9 mix, followed by those treated with S9 mix alone and those with fecalase or FM. Freeze-dried FM was more stable in storage than fecalase. Based on these findings, FM could be usable instead of human fecalase in the Ames test.

• Journal of Ginseng Research
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• 제33권2호
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• pp.93-98
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• 2009

To understand the anti-allergic mechanism of compound K, which is a metabolite of ginsenoside Rb1, a main constituent of the root of Panax ginseng C.A. Meyer (family Araliaceae), its inhibitory effect against IgE-antigen complex IAC)-induced passive cutaneous anaphylaxis (PCA) reaction in mice and mRNA and protein expressions of allergic cytokines in lAC-stimulated RBL-2H3 cells were investigated. Orally administered ginsenoside Rb1 more potently inhibited PCA reaction when administered at 5 h prior to the lAC treatment than when administered at I h before. However, compound K orally administered 1 h before lAC treatment showed a more potent anti-PCA reaction effect than when treated at 5 h before. Orally administered ginsenoside Rb1 more potently inhibited PCA reaction induced by lAC in mice than intraperitoneally treated one, apart from orally administered its metabolite, compound K, which was more potent than the orally administered one. The compound K, a metabolite of ginsenoside Rb1, inhibited mRNA and protein expressions of IL-4 and TNF-${\alpha}$ and the activation of their transcription factor NF-$\kappa$B and MAPK in lAC-stimulated RBL-2H3 cells. These findings suggest that orally administered ginsenoside Rb1 may be dependent on its metabolism by intestinal microflora in the intestine and the compound K may improve allergic diseases by the inhibition of IL-4 and TNF-${\alpha}$ expresseion.