• Journal of Pharmaceutical Investigation
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• v.6 no.1
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• pp.18-25
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• 1976

The purpose of this investigation was to determine the effect of ethanol on the absorption, excretion and protein binding of sulfadimethoxine from the small intestine of the rat and rabbit. The results are as follows: 1. The rat small intestinal absorption of sulfadimethoxine was increased by 0.5% and 2% ethanol. 2. Blood level of sulfadimethoxine after oral administration was significantly elevated (p<0.01) by 0.5g/kg and 1g/kg ethanol respectively, but was significantly inhibited by 3g/kg ethanol from that of the control. 3. Ethanol gave the effect on the clearance of sulfadimethoxine, which was increased by ethanol from that of control. 4. In the protein binding rate, it was found that ethanol decreased protein binding of sulfadimethoxine except 0.1% and 0.5% ethanol.

• YAKHAK HOEJI
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• v.34 no.2
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• pp.126-132
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• 1990

To enhance the activity of ibuprofen, amides of ibuprofen, 1-piperazinyl-2-(4-isobutylphenyl)propionamide(Ibu-P.A.) and 1-(4-methylpiperazinyl)-2-(4-isobutylphenyl)propionamide (Ibu-M.P.), were synthesized and the pharmaceutical properties and the pharmacological activities of the amides were studied. The lipid:water partition coefficients and pKa values were examined in vitro, and the antiinflammatory effect, analgesic effects, acute toxicity, and intestinal absorption were studied for the amides and compared with ibuprofen in vivo. The results are summarized as belows; 1) The lipid:water partition coefficients of Ibu-M.P. were higher than those of ibuprofen. 2) The calculated pKa values of ibuprofen and Ibu-M.P. were 5.49 and 8.66, respectively. 3) The antiinflammatory effects of ibuprofen, Ibu-P.A., and Ibu-M.P. were same intensity, but the duration of the effects of Ibu-P.A. and Ibu-M.P. were longer than that of ibuprofen. 4) The analgesic effect of Ibu-M.P. was more potent than those of ibuprofen and Ibu-P.A. in the acetic acid-induced writhing test. 5) The $LD_{50}$ was 495 mg/kg for ibuprofen, 187 mg/kg for Ibu-M.P., and over 1250 mg/kg for Ibu-P.A.. 6) The absorption rate constants(k) and half-life($t_{1/2}$) were 0.74($hr^{-1}$) and 0.94(hr) for ibuprofen, and 0.72 ($hr^{-1}$) and 0.96 (hr) respectively for Ibu-M.P..

• Journal of Ginseng Research
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• v.39 no.2
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• pp.183-187
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• 2015

Background: Gut microflora play a crucial role in the biotransformation of ginsenosides to compound K (CK), which may affect the pharmacological effects of ginseng. Prebiotics, such as NUTRIOSE, could enhance the formation and consequent absorption of CK through the modulation of gut microbial metabolic activities. In this study, the effect of a prebiotic fiber (NUTRIOSE) on the pharmacokinetics of ginsenoside CK, a bioactive metabolite of ginsenosides, and its mechanism of action were investigated. Methods: Male Sprague-Dawley rats were given control or NUTRIOSE-containing diets (control diet + NUTRIOSE) for 2 wk, and ginseng extract or vehicle was then orally administered. Blood samples were collected to investigate the pharmacokinetics of CK using liquid chromatography-tandem mass spectrometry. Fecal activities that metabolize ginsenoside Rb1 to CK were assayed with fecal specimens or bacteria cultures. Results: When ginseng extract was orally administered to rats fed with 2.5%, 5%, or 10% NUTRIOSE containing diets, the maximum plasma concentration ($C_{max}$) and area under the plasma concentration-time curve values of CK significantly increased in a NUTRIOSE content-dependent manner. NUTRIOSE intake increased glycosidase activity and CK formation in rat intestinal contents. The CK-forming activities of intestinal microbiota cultured in vitro were significantly induced by NUTRIOSE. Conclusion: These results show that prebiotic diets, such as NUTRIOSE, may promote the metabolic conversion of ginsenosides to CK and the subsequent absorption of CK in the gastrointestinal tract and may potentiate the pharmacological effects of ginseng.

• Journal of Ginseng Research
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• v.38 no.3
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• pp.203-207
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• 2014

Background: There is limited understanding of the effect of dietary components on the absorption of ginsenosides and their metabolites into the blood. Methods: This study investigated the pharmacokinetics of the ginseng extract and its main constituent ginsenoside Rb1 in rats with or without pretreatment with a prebiotic fiber, NUTRIOSE, by liquid chromatography tandem mass spectrometry. When ginsenoside Rb1 was incubated with rat feces, its main metabolite was ginsenoside Rd. Results: When the intestinal microbiota of rat feces were cultured in vitro, their ginsenoside Rd-forming activities were significantly induced by NUTRIOSE. When ginsenoside Rb1 was orally administered to rats, the maximum plasma concentration (Cmax) and area under the plasma drug concentratione-time curve (AUC) for the main metabolite, ginsenoside Rd, were $72.4{\pm}31.6ng/mL$ and $663.9{\pm}285.3{\mu}g{\cdot}h/mL$, respectively. When the ginseng extract (2,000 mg/kg) was orally administered, Cmax and AUC for ginsenoside Rd were $906.5{\pm}330.2ng/mL$ and $11,377.3{\pm}4,470.2{\mu}g{\cdot}h/mL$, respectively. When ginseng extract was orally administered to rats fed NUTRIOSE containing diets (2.5%, 5%, or 10%), Cmax and AUC were increased in the NUTRIOSE receiving groups in a dose-dependent manner. Conclusion: These findings reveal that intestinal microflora promote metabolic conversion of ginsenoside Rb1 and ginseng extract to ginsenoside Rd and promote its absorption into the blood in rats. Its conversion may be induced by prebiotic diets such as NUTRIOSE.

• Journal of Microbiology and Biotechnology
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• v.31 no.9
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• pp.1295-1304
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• 2021

Modified Renshen Wumei decoction (MRWD), a famous traditional Chinese medicine, is widely used for treating persistent diarrhea. However, as the mechanism by which MRWD regulates diarrhea remains unknown, we examined the protective effects of MRWD on intestinal barrier integrity in a diarrhea model. In total, 48 male rats were randomly distributed to four treatment groups: the blank group (CK group), model group (MC group), Medilac-Vita group (MV group) and Chinese herb group (MRWD group). After a 21-day experiment, serum and colon samples were assessed. The diarrhea index, pathological examination findings and change in ᴅ-lactate and diamine oxidase (DAO) contents illustrated that the induction of diarrhea caused intestinal injury, which was ameliorated by MV and MRWD infusion. Metabolomics analysis identified several metabolites in the serum. Some critical metabolites, such as phosphoric acid, taurine, cortisone, leukotriene B4 and calcitriol, were found to be significantly elevated by MRWD infusion. Importantly, these differences correlated with mineral absorption and metabolism and peroxisome proliferator-activated receptor (PPAR) pathways. Moreover, it significantly increased the expression levels of TLR4, MyD88 and p-NF-κB p65 proteins and the contents of IL-1 and TNF-α, while the expression levels of occludin, claudin-1 and ZO-1 proteins decreased. These deleterious effects were significantly alleviated by MV and MRWD infusion. Our findings indicate that MRWD infusion helps alleviate diarrhea, possibly by maintaining electrolyte homeostasis, improving the intestinal barrier integrity, and inhibiting the TLR4/NF-κB axis.

• Journal of Biosystems Engineering
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• v.40 no.1
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• pp.78-88
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• 2015

Purpose: The objective of this study is to review researches regarding factors that potentially affect adolescent calcium (Ca) metabolism, and to suggest a potential modeling approach for optimizing gastrointestinal Ca absorption and peak bone mass. Background: Optimal gastrointestinal Ca absorption is a key to maximizing peak bone mass in adolescents. Urine Ca excretion in adolescents rises only after bone accretion is saturated, indicating that higher intestinal Ca absorption and bone retention is necessary to ensure maximum bone accretion. Hence, maximizing peak bone mass is possible by controlling the factors influencing gastrointestinal Ca absorption and bone accretion. However, a mechanism that explains the unique adolescent Ca metabolism has not yet been elucidated. Review: Dietary factors that enhance gastrointestinal Ca absorption may increase the available Ca pool usable for bone accretion, and a specific hormone may direct optimal Ca utilization to maximize peak bone mass. IGF-1 is an endocrine hormone whose levels peak during adolescence and increase fractional Ca absorption and bone Ca accretion. Prebiotics, generally obtained from dietary sources, have been reported to exert a beneficial effect on Ca absorption via microbiota activity. We selected and reviewed three candidates that could be used to propose a comprehensive Ca metabolic model for optimal Ca absorption and peak bone mass in adolescents. Modeling: Modeling has been used to investigate Ca metabolism and its regulators. Herein, we reviewed previous Ca modeling studies. Based on this review, we proposed a method for developing a comprehensive model that includes regulatory effectors of IGF-1 and prebiotics.

• BMB Reports
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• v.51 no.9
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• pp.429-436
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• 2018

Fructose in the form of sucrose and high fructose corn syrup is absorbed by the intestinal transporter and mainly metabolized in the small intestine. However, excess intake of fructose overwhelms the absorptive capacity of the small intestine, leading to fructose malabsorption. Carbohydrate response element-binding protein (ChREBP) is a basic helix-loop-helix leucine zipper transcription factor that plays a key role in glycolytic and lipogenic gene expression in response to carbohydrate consumption. While ChREBP was initially identified as a glucose-responsive factor in the liver, recent evidence suggests that ChREBP is essential for fructose-induced lipogenesis and gluconeogenesis in the small intestine as well as in the liver. We recently identified that the loss of ChREBP leads to fructose intolerance via insufficient induction of genes involved in fructose transport and metabolism in the intestine. As fructose consumption is increasing and closely associated with metabolic and gastrointestinal diseases, a comprehensive understanding of cellular fructose sensing and metabolism via ChREBP may uncover new therapeutic opportunities. In this mini review, we briefly summarize recent progress in intestinal fructose metabolism, regulation and function of ChREBP by fructose, and delineate the potential mechanisms by which excessive fructose consumption may lead to irritable bowel syndrome.

• Asian-Australasian Journal of Animal Sciences
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• v.21 no.12
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• pp.1773-1778
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• 2008

Two experiments were carried out to study the effects of corticosterone (CORT) administration on intestinal morphology and function of broilers. In both experiments, birds were randomly divided into two equal groups. One group was the control group (CTRL), and the birds were fed with a basal diet. The other was the experimental group (CORT), and the birds were fed with the basal diet plus 30 mg of CORT/kg diet. At 21 days of age, performance, morphological characteristics of intestine, D-xylose level in plasma, activities of digestive enzymes in digesta, digestibility of nutrients and 5-bromo-2-deoxyuridine (BrdUrd)-labeling index of intestinal epithelial cells were determined. CORT administration decreased feed intake, daily gain and feed conversion ratio (p<0.05). CORT also decreased duodenal and jejunal villus height (p<0.05) as well as crypt depth (p<0.05). The D-xylose level in plasma of CORT-treated broilers was lower than that of the control (p<0.05). CORT treatment caused a decrease in apparent digestibility of protein (p<0.05), whereas fat and starch apparent digestibilities were unaffected (p>0.05). CORT administration increased activities of trypsin and amylase (p<0.05), and decreased BrdUrd-labeling index of duodenal and jejunal epithelial cells (p<0.05). In conclusion, CORT administration impaired the normal morphology and absorptive capacity of the small intestine of broiler chickens.

• Journal of Society of Preventive Korean Medicine
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• v.15 no.2
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• pp.1-19
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• 2011

Toxicokinetics of Korean Traditional Medicines(TKM) is the description of what rate TKM will enter the body and what happens to it once it is in the body in terms of toxicology. However, it is not easy to understand TKM toxicokinetics because of various factors such as a mixture of 2-30 kinds of herbal materials containing thousands of chemicals, and complex chemical properties. For these reasons, little is known about toxicokinetics of TKM. This study was aimed to characterize and review the absorption, distribution and metabolism of korean traditional medicines in a view of toxicokinetics. For this aim, some of korean traditional medicines were reviewed on a basis of drug-drug interaction, biotransformation and intestinal metabolisms by bacteria. As the factors affecting mainly on toxicokinetics of TKM, individual herbal material's degree of lipophilicity and metabolic rate, and decoction components according to different kinds of herbal materials were considered. Other factors such as intestinal pH and bacterial activity for metabolism affecting on TKM toxicokinetics, especially in small intestine. It would be a better way for improving the adverse or poor effects caused by TCM if the factors affecting on toxicokinetics of TKM is considered.

• Asian-Australasian Journal of Animal Sciences
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• v.9 no.5
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• pp.539-550
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• 1996

Experiment was conducted to study the effect of sources of dietary fiber on the intestinal morphology of geese. Sixty white Roman geese of two-week-old were divided randomly into six groups and were fed with isoenergetic and isonitrogenous diets which contain alfalfa meal, barley hull, rice hull, purified cellulose, lignin, or pectin as the major dietary source of fiber. Different sources of dietary fiber significantly influenced the villi height and the crypt depth in the duodenum, and the villi height and the muscle layer thickness in the ileum (p < 0.05). The duodenal villus in the geese that fed diets with alfalfa meal, rice hull or pectin supplemented were significantly longest ($968.5{\mu}m$), whereas the lignin group was significantly shortest villus and deepest crypt depth (p < 0.05). The thicknesses of the ileal and caecal muscle layer were significantly thicker in the geese fed with cellulose supplemented diets than in those fed with the other treatment diets. The caecum of the barley bran fed geese possessed significantly longest villi and the most thick muscle layers (p < 0.05). From scanning electronic microscopic observation, the leafy and plate-like in the duodenal villi morphology of geese represented a more effective nutrient absorption in the small intestine. The morphology of ileal villi in geese was similar from herbivorous rabbit and from the African Green monkey.