• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1997년도 춘계학술대회
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• pp.119-119
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• 1997

Valacyclovir is a L-valyl ester prodrug of acyclovir which is a highly effective and selective antiviral agent in the treatment of herpes virus diseases. Valacyclovir is rapidly and almost completely converted to acyclovir and increases the oral bioavailability of acyclovir three to five fold. However, the intestinal absorption mechanism of valacyclovir is not clear. If the improved absorption mechanism of valacyclovir is fully understood, it will provide a rationale of designing the amino acid ester prodrugs of polar drugs containing hydroxyl group. The main objective of our present study is to characterize the membrane transport mechanism of valacyclovir. Methods : Intestinal absorption of valacyclovir was investigated by using in-situ rat perfusion study and its wall permeability was estimated by modified boundary layer model. The membrane transport mechanism was also investigated through the uptake study in Caco-2 cells and in CHO-hPepTl cells. Results : In the rat perfusion study, the wall permeability of valacyclovir was ten times higher than acyclovir and showed concentration dependency, Valacyclovir also demonstrated a D,L stereo-selectivity with L-isomer having an approximately five-fold higher permeability than D-isomer. Mixed dipeptides and cephalexin, which are transported by dipeptide carriers, strongly competed with valacyclovir for the intestinal absorption, while L-valine did not show any competition with valacyclovir. This indicated that the intestinal absorption of valacyclovir could be dipeptide carrier-mediated. In addition, the competitive uptake study in Caco-2 cells presented that dipeptides reduced the valacyclovir uptake but valine did not. Also, in IC$\sub$50/ study, valacyclovir showed strong inhibition on the $^3$H-gly-sar uptake in CHO-hPepTl cells over-expressing a human intestinal peptide transporter. Taken together, the result from our present study indicated that valacyclovir utilized the peptide transporter for the intestinal absorption.

• 대한임상검사과학회지
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• 제54권3호
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• pp.217-223
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• 2022

다양한 건강기능식품 중 프로바이오틱스는 전 세계적으로 가장 방대한 시장을 이루고 있으며, 장 건강이 우리 몸의 전반적인 면역작용을 조절하며 질병을 예방하고, 나아가 치료에 도움을 줄 수 있다는 연구결과에 따라 지속적으로 프로바이오틱스에 대한 관심이 증가하고 있다. 본 연구에서는 무화과식초가 가진 항균능을 이용하여 유제품과 드레싱 소스를 개발하여 그 선호도를 조사하고 대장세포에 미치는 영향을 분석하고자 하였다. 일반우유에 5% 무화과식초를 첨가하였을 때 마시는 요거트와 리코타치즈에 대한 가장 만족도가 높았다. 제조된 유제품에서 분리한 균은 Leuconostoc lactis이며 1.0×10⁷~1.0×10⁸ CFU/mL 이상의 세균수가 측정되어 식품의 기준 및 규격의 기준치를 만족하였다. 인체의 소장 상피세포와 흡사하게 증식되는 Caco-2 세포주에서 세포생존율을 관찰한 결과, 유청을 10% 농도로 처리하였을 때 세포생존율이 19% 가량 유의적으로 증가하였다. 농도별로 유청을 처리하였을 때 최대 58%의 항산화능을 보였다. 또한 유청에서 분리된 Leuconostoc lactis는 우수한 부착능이 관찰됨에 따라 장건강에 도움을 주는 유제품임을 확인하였다.

• Nutrition Research and Practice
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• 제9권1호
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• pp.3-10
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• 2015

BACKGROUND/OBJECTIVES: Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, involves chronic inflammation of the gastrointestinal tract. Previously, Sasa quelpaertensis leaves have been shown to mediate anti-inflammation and anti-cancer effects, although it remains unclear whether Sasa leaves are able to attenuate inflammation-related intestinal diseases. Therefore, the aim of this study was to investigate the anti-inflammatory effects of Sasa quelpaertensis leaf extract (SQE) using an in vitro co-culture model of the intestinal epithelial environment. MATERIALS/METHODS: An in vitro co-culture system was established that consisted of intestinal epithelial Caco-2 cells and RAW 264.7 macrophages. Treatment with lipopolysaccharide (LPS) was used to induce inflammation. RESULTS: Treatment with SQE significantly suppressed the secretion of LPS-induced nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$), IL-6, and IL-$1{\beta}$ in co-cultured RAW 264.7 macrophages. In addition, expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and tumor necrosis factor (TNF)-${\alpha}$ were down-regulated in response to inhibition of $I{\kappa}B{\alpha}$ phosphorylation by SQE. Compared with two bioactive compounds that have previously been identified in SQE, tricin and P-coumaric acid, SQE exhibited the most effective anti-inflammatory properties. CONCLUSIONS: SQE exhibited intestinal anti-inflammatory activity by inhibiting various inflammatory mediators mediated through nuclear transcription factor kappa-B (NF-kB) activation. Thus, SQE has the potential to ameliorate inflammation-related diseases, including IBD, by limiting excessive production of pro-inflammatory mediators.

• Preventive Nutrition and Food Science
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• 제16권2호
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• pp.135-141
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• 2011

Inhibition of intestinal glucose uptake is beneficial in reducing the blood glucose level for diabetes. To search for an effective intestinal glucose uptake inhibitor from natural sources, 70 native edible plants, fruits and vegetables were screened using Caco-2 cells and fluorescent D-glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose (2-NBDG). A compound that was able to inhibit glucose uptake was isolated from methanol extract of Punica granatum L. and called PG-1a. PG-1a appears to be a phthalic acid-diisononyl ester- like compound (PDE) with molecular weight of 418. The inhibitory effect of PG-1a on intestinal glucose uptake was dose-dependent with 89% inhibition at $100\;{\mu}g$/mL. Furthermore, the intestinal glucose uptake inhibitory effect of PG-1a was 1.2-fold higher than phlorizin, a well known glucose uptake inhibitor. This study suggests that PG-1a could play a role in controlling the dietary glucose absorption, and that PG-1a can effectively improve the diabetic condition, and may be used as an optional therapeutic and preventive agent.

• Asian Pacific Journal of Cancer Prevention
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• 제17권11호
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• pp.4929-4934
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• 2016

Cancer, a worldwide epidemic disease with diverse origins, involves abnormal cell growth with the potential to invade other parts of the body. Globally, it is the main cause of mortality and morbidity. To overcome the drawbacks of the commercially available chemotherapies, natural products-loaded nano-composites are recommended to improve cancer targetability and decrease the harmful impact on normal cells. This study aimed at exploring the anti-cancer impacts of Moringa oleifera seed oil in its free- (MO) and nano-formulations (MOn) through studying whether it mechanistically promotes mitochondrial apoptosis-mediating cell death. Mitochondrial-based cytotoxicity and flow cytometric-based apoptosis analyses were performed on cancer HepG2, MCF7, HCT 116, and Caco-2 cell lines against normal kidney BHK-21 cell line. The present study resulted that MOn triggered colorectal cancer Caco-2 and HCT 116 cytotoxicity via mitochondrial dysfunction more powerful than its free counterpart (MO). On the other side, MOn and MO remarkably induces HCT 116 mitochondrial apoptosis, while sparing normal BHK-21 cells with minimal cytotoxic effect. The present results concluded that nano-micelle of Moringa oleifera seed oil (MOn) can provide a novel therapeutic approach for colorectal and breast cancers via mitochondrial-mediated apoptosis, while sparing normal and even liver cancer cells a bit healthy or with minimal harmful effect. Intriguingly, MOn induced breast cancer not hepatocellular carcinoma cell death.

• 한국미생물·생명공학회지
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• 제49권2호
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• pp.157-166
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• 2021

The probiotic market is constantly continuing to grow, concomitantly with a widening in the range and diversity of probiotic products. Probiotics are defined as live microorganisms that provide a benefit to the host when consumed at a proper dose; the viability of a probiotic is therefore of crucial importance for its efficacy. Many products undergo lyophilization for maintaining their shelf-life. Unfortunately, this procedure may damage the integrity of the cells due to stress conditions during both the freezing and (vacuum-) drying process, thereby impacting their functionality. We propose a lysine-based mixture for rehydration of freeze-dried probiotics for improving their viability during in vitro simulated gastric and duodenum stress conditions. Measurement of the zeta potential served as an indicator of cell integrity and efficacy of this mixture, while functionality was estimated by adhesion to a human enterocyte-like Caco-2 cell-line. The freeze-dried bacteria exhibited a significantly different zeta potential compared to fresh cultures; however, this condition could be restored by rehydration with the lysine mixture. Recovery of the surface charge was found to influence adhesion ability to the Caco-2 cell-line. The optimum lysine concentration of the formulation, designated "Zeta-bio", was found to be 0.03 M for improving the viability of Lactiplantibacillus plantarum Lp-115 by up to 13.86% and a 7-strain mixture (400B) to 41.99% compared to the control rehydrated with distilled water. In addition, the lysine Zeta-bio formulation notably increased the adherence ability of lyophilized Lp-115 to the Caco-2 cell-line after subjected to the in vitro stress conditions of the simulated gastrointestinal tract passage.

• Food Science and Biotechnology
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• 제17권6호
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• pp.1235-1239
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• 2008

To study the health promoting effects of medicinal plants, 30 medicinal plants commonly available in Korea have been evaluated for their antioxidant compounds and antioxidant and antiproliferative activities. Total polyphenolics and flavonoids in the methanolic extracts were measured by spectrophotometric methods and 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging activities and chelating effects have been determined for antioxidant activities. Moreover, the effects of medicinal plants on cell proliferation of intestinal (Caco-2) and pituitary (GH3) tumor cells were investigated using thiazolyl blue terazolium bromide (MIT) assay. The methanolic extracts of Pueraria thunbergiana and Artemisiae asiatria contained the highest total polyphenolic and flavonoid contents, respectively. P. thunbergiana exhibited the highest antioxidant activities. A. asiatria showed the strongest antiproliferative activity against Caco-2 and Ponciruc trifoliata Rafin and Lophathrum gracile Bronghiart exhibited the highest activities against GH3. Although there was positive correlation between ABTS radical scavenging activity and polyphenolic contents ($R^2=8189$), no relationship was found between antiproliferative and antioxidant activities.

• Food Science and Biotechnology
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• 제15권2호
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• pp.227-231
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• 2006

Strain NK181 was isolated for probiotic use from jeotkal and based on results of API 50 CHL kit and 16S rDNA sequencing was tentatively named Lactobacillus plantarum NK181. L. plantarum NK181 was highly resistant to artificial gastric juice (pH 2.5) and bile acid and demonstrated strong adherence to Caco-2 cells. In test using API ZYM kit, eight enzymes were produced. Supernatant of L. plantarum NK181 exhibited about 30% 1,1-diphenyl-2-picyryl hedrazyl (DPPH) radical-scavenging activity and reduced cholesterol by 70%. These results demonstrate potential use of L. plantarum NK181 as health-promoting probiotic.

• Archives of Pharmacal Research
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• 제26권12호
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• pp.1102-1108
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• 2003

We studied the effects of phytolaccosides, saponins from Phytolacca americana, on the intestinal absorption of heparin in vitro and in vivo. The absorption enhancing activity of these compounds (phytolaccosides B, $D_2$, E, F, G and I) was determined by changes in transepithelial electrical resistance (TEER) and the transport amount of heparin disaccharide, the major repeating unit of heparin, across Caco-2 cell monolayers. With the exception of phytolaccoside G, all of them decreased TEER values and increased the permeability in a dose-dependent and time-dependent manner. In vitro, phytolaccosides B,$D_2$, and E showed significant absorption enhancing activities, while effects by phytolaccoside F and I were mild. In vivo, phytolaccoside E increased the activated partial thromboplastin time (APTT) and thrombin time, indicating that phytolaccoside E modulated the transport of heparin in intestinal route. Our results suggest that a series of phytolaccosides from Phytolacca americana can be applied as pharmaceutical excipients to improve the permeability of macromolecules and hydrophilic drugs having difficulty in absorption across the intestinal epithelium.

• Asian Pacific Journal of Cancer Prevention
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• 제15권4호
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• pp.1807-1810
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• 2014

Background: It is known that inducible nitric oxide synthase (iNOS)/nitric oxide (NO) plays an integral role during intestinal inflammation, an important factor for colon cancer development. Natural compounds from Curcuma longa L. (Zingiberaceae) have long been a potential source of bioactive materials with various beneficial biological functions. Among them, a major active curcuminoid, demethoxycurcumin (DMC) has been shown to possess anti-inflammatory properties in lipopolysaccharide (LPS)-activated macrophages or microglia cells. However, the role of DMC on iNOS expression and NO production in an in vitro inflamed human intestinal mucosa model has not yet been elucidated. This study concerned inhibitory effects on iNOS expression and NO production of DMC in inflamed human intestinal Caco-2 cells. An in vitro model was generated and inhibitory effects on NO production of DMC at 65 ${\mu}M$ for 24-96 h were assessed by monitoring nitrite levels. Expression of iNOS mRNA and protein was also investigated. DMC significantly decreased NO secretion by 35-41% in our inflamed cell model. Decrease in NO production by DMC was concomitant with down-regulation of iNOS at mRNA and protein levels compared to proinflammatory cytokine cocktail and LPS-treated controls. Mechanism of action of DMC may be partly due to its potent inhibition of the iNOS pathway. Our findings suggest that DMC may have potential as a therapeutic agent against inflammation-related diseases, especially in the gut.