scholarly journals Absorption and Transport Characteristics and Mechanisms of Carnosic Acid

Biology ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1278
Author(s):  
Xuexiang Chen ◽  
Meigui Huang ◽  
Dongmei Liu ◽  
Yongze Li ◽  
Qiu Luo ◽  
...  
Keyword(s):  
Cell Model ◽  
Cell Monolayer ◽  
Scientific Basis ◽  
Carnosic Acid ◽  
Intestinal Epithelial ◽  
Apparent Permeability ◽  
Beneficial Effects ◽  
Single Cell Model ◽  
Relevant Dose ◽  
Apparent Permeability Coefficient

Carnosic acid (CA) is a phenolic diterpenoid mainly found in rosemary and sage. CA has been reported to possess health-beneficial effects in various experimental settings. Herein, a mouse experiment and Caco-2 single-cell model were used to understand the absorption and transport characteristics of CA. First, we determined the tissue distribution of CA in mice, following an oral gavage at a physiologically relevant dose. We found that CA was bioavailable systemically and present locally in the digestive tract, especially in the cecum and colon. Next, we thought to characterize the absorption and transport of CA in the Caco-2 cell monolayer model of the intestinal epithelial barrier. In the Caco-2 cell model, CA exhibited a moderate permeability and was subjected to a mild efflux. Moreover, the apparent permeability coefficient (Papp) of CA transported across Caco-2 cell monolayers was significantly changed when the inhibitors of specific active transporter and passive diffusion were added to cells, suggesting that the absorption and transport of CA involved both passive and active transportation. The present study is an important first step towards understanding the absorption, transport, and metabolic mechanisms of CA. This could provide the scientific basis for developing CA-containing functional foods or dietary supplements with improved bioavailability.

scholarly journals Bioavailability Studies of BioTurmin-WD (Water Dispersible Curcuminoids) Using Caco-2 Cell Model

2014 ◽  
Vol 3 (3) ◽  
pp. 158 ◽  
Author(s):  
H. N. Shivaprasad ◽  
M. Bhanumathy ◽  
Subrata Pandit ◽  
D. Manohar ◽  
B. Pavan Kumar ◽  
...  
Keyword(s):  
Cell Model ◽  
Curcuma Longa ◽  
Cell Monolayer ◽  
Absorption Capacity ◽  
Apparent Permeability ◽  
Water Dispersible ◽  
Therapeutic Value ◽  
Clinical Benefits ◽  
Apparent Permeability Coefficient

<p>Curcuminoids is the mixture of curcumin, demethoxycurcumin and bisdemethoxycurcumin obtained from dried rhizomes of <em>Curcuma longa, </em>commonly used for its wide therapeutic value. However, the absorption efficacy of curcuminoids is too low to exhibit its proper therapeutic value. Thus, a new preparation named as BioTurmin-WD (water dispersible curcuminoids) was developed for improved bioavailability. By using human Caco-2 cell monolayer, the permeability efficacy of BioTurmin-WD was evaluated and compared with that of 95% pure curcuminoids. Caco-2 model predicts the<em> in vivo </em>absorption of drugs across the gut wall by measuring the rate of transport of a compound across the Caco-2 cell line. BioTurmin-WD was added to the apical layer and basolateral samples were collected over 120 min to examine the concentration diffusing across the cell monolayer. Permeable curcuminoids across the cell monolayer was analysed through reverse phase high pressure liquid chromatography (RP-HPLC). Apparent permeabilities (P<sub>app</sub>) of BioTurmin-WD and 95% curcuminoids were found to be 5.89 × 10<sup>-6</sup> and 2.65 × 10<sup>-6</sup> cm/s respectively. The apparent permeability coefficient of BioTurmin-WD was 7.03-fold higher than 95% pure curcuminoids. Percentage permeability of BioTurmin-WD (0.2945) was much higher than 95% curcuminoids (0.0859). Results indicated that BioTurmin-WD have a much higher absorption capacity (bioavailability) compared to 95% pure curcuminoids. Thus, BioTurmin-WD may be useful as a dietary supplement with greater bioavailability to exert clinical benefits in humans at a lower dosage.</p>

scholarly journals A Miniaturized Pump Out Method for Characterizing Molecule Interaction with ABC Transporters

2019 ◽  
Vol 20 (22) ◽  
pp. 5529 ◽  
Author(s):  
Emmanuel Sevin ◽  
Lucie Dehouck ◽  
Romain Versele ◽  
Maxime Culot ◽  
Fabien Gosselet
Keyword(s):  
Abc Transporters ◽  
Detection Method ◽  
Cell Model ◽  
Early Stage ◽  
Cell Monolayer ◽  
Efflux Pumps ◽  
Apparent Permeability ◽  
Traditional Use ◽  
Molecule Design ◽  
Molecule Interaction

Characterizing interaction of newly synthetized molecules with efflux pumps remains essential to improve their efficacy and safety. Caco-2 cell line cultivated on inserts is widely used for measuring apparent permeability of drugs across biological barriers, and for estimating their interaction with efflux pumps such as P-gp, BCRP and MRPs. However, this method remains time consuming and expensive. In addition, detection method is required for measuring molecule passage across cell monolayer and false results can be generated if drugs concentrations used are too high as demonstrated with quinidine. For this reason, we developed a new protocol based on the use of Caco-2 cell directly seeded on 96- or 384-well plates and the use of fluorescent substrates for efflux pumps. We clearly observed that the new method reduces costs for molecule screening and leads to higher throughput compared to traditional use of Caco-2 cell model. This accelerated model could provide quick feedback regarding the molecule design during the early stage of drug discovery and therefore reduce the number of compounds to be further evaluated using the traditional Caco-2 insert method.

scholarly journals Preparation and investigation of mefenamic acid – polyethylene glycol – sucrose ester solid dispersions

2015 ◽  
Vol 65 (4) ◽  
pp. 453-462 ◽  
Author(s):  
Ibolya Fülöp ◽  
Árpád Gyéresi ◽  
Lóránd Kiss ◽  
Mária A. Deli ◽  
Mircea Dumitru Croitoru ◽  
...  
Keyword(s):  
Polyethylene Glycol ◽  
Mefenamic Acid ◽  
Water Solubility ◽  
Solid Dispersions ◽  
Intestinal Epithelial ◽  
Sucrose Esters ◽  
Apparent Permeability ◽  
Apparent Permeability Coefficient ◽  
Cell Layers ◽  
The Difference

Abstract Mefenamic acid (MA) is a widely used non-steroidal antiinflammatory (NSAID) drug. The adverse effects typical of NSAIDs are also present in the case of MA, partly due to its low water solubility. The aim of this study was to increase the water solubility of MA in order to influence its absorption and bioavailability. Solid dispersions of MA were prepared by the melting method using polyethylene glycol 6000 and different types (laurate, D-1216; palmitate, P-1670; stearate, S-1670) and amounts of sucrose esters as carriers. The X-ray diffraction results show that MA crystals were not present in the products. Dissolution tests carried out in artificial intestinal juice showed that the product containing 10 % D-1216 increased water solubility about 3 times. The apparent permeability coefficient of MA across human Caco-2 intestinal epithelial cell layers was high and, despite the difference in solubility, there was no further increase in drug penetration in the presence of the applied additives.

scholarly journals Intestinal Transportations of Main Chemical Compositions of Polygoni Multiflori Radix in Caco-2 Cell Model

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Jie Yu ◽  
Na Li ◽  
Pei Lin ◽  
Yunfei Li ◽  
Xiaojian Mao ◽  
...  
Keyword(s):  
Gibbs Energy ◽  
Cell Model ◽  
Cell Monolayer ◽  
Intestinal Transport ◽  
Transepithelial Transport ◽  
Chemical Compositions ◽  
Polygonum Multiflorum ◽  
Close Attention ◽  
Apparent Permeability ◽  
Cell Monolayers

Context. Polygoni Multiflori Radix (PMR) is originated from the root ofPolygonum multiflorumThunb. and used in oriental countries for centuries. However, little researches pay close attention to the absorption of its major constituents.Objective. Transepithelial transport of TSG, RL, PL, and four anthraquinones is carried out.Materials and Methods. Caco-2 cell monolayer, which represented a well-established model for the study of intestinal transport of nutrients and xenobiotics, was used in this paper.Results. The apparent permeability coefficients (Papp) in the Caco-2 cell monolayers were TSG (2.372 × 10−9) < EG (2.391 × 10−9) < EN (2.483 × 10−9) < PL (4.917 × 10−9) < RN (1.707 × 10−8) < RL (1.778 × 10−8) < AE (1.952 × 10−8). Thus, RN, RL, and AE were considered partly absorbed, while other constituents were hardly absorbed.Discussion and Conclusion. Glycosides showed poor permeabilities than aglycones. In the meantime, TSG and EN gave out poor recovery rates in this assay, which indicated that TSG and EN may accumulate or metabolise in the Caco-2 cells.In silicoprediction indicated that Gibbs energy (r=0.751,p<0.05) and heat of form (r=0.701,p<0.05) were strongly positively correlated withPapp.

Bioaccessibility in daily diet and bioavailability in vitro of aflatoxins from maize after cooking

2019 ◽  
Vol 12 (2) ◽  
pp. 173-181 ◽  
Author(s):  
X. Lin ◽  
X. Hu ◽  
Y. Zhang ◽  
Y. Xia ◽  
M. Zhang
Keyword(s):  
Cell Model ◽  
Intestinal Transport ◽  
In Vitro Digestion ◽  
Food Type ◽  
Apparent Permeability ◽  
Steam Cooking ◽  
Degradation Rates ◽  
Apparent Permeability Coefficient ◽  
Aflatoxin B

Bioavailability is not a constant percentage of a contaminant in food but is affected by many factors, such as food type, treatment, diet structure and interaction with other compounds. To evaluate these influences, we measured the bioaccessibility of aflatoxins from nine naturally polluted maize samples, collected from southeast China, using an in vitro digestion model, and analysed the intestinal transport of aflatoxins by a Caco-2 cell model. Steam cooking treatment could reduce the aflatoxin levels in maize bread. The degradation rates of aflatoxin B1, aflatoxin B2, aflatoxin G1, and aflatoxin G2 ranged from 24.9±3.2 to 33.9±3.5%, 27.0±2.0 to 39.0±1.8%, 27.9±7.9 to 34.4±8.2% and 25.6±3.6 to 37.2±6.5%, respectively. As a result, the bioaccessibility of aflatoxins determined by an in vitro digestion model (41.5-63.3%) was much lower than the previously reported 80%. Edible oil could increase the bioaccessibility of aflatoxin, whereas lettuce would decrease the exposure amount from maize. With a Caco-2 cell model, the apparent permeability coefficient exceeding 10-5 cm/s indicated that there is high absorption of aflatoxins in the human body, while the intestinal transport can be effectively restrained in the presence of chlorophyll.

scholarly journals Comparison of the uptake and secretion of carotene and xanthophyll carotenoids by Caco-2 intestinal cells

2007 ◽  
Vol 98 (1) ◽  
pp. 38-44 ◽  
Author(s):  
Laurie O'Sullivan ◽  
Lisa Ryan ◽  
Nora O'Brien
Keyword(s):  
Antioxidant Capacity ◽  
Cellular Uptake ◽  
Cell Model ◽  
Cell Monolayer ◽  
Intestinal Cells ◽  
Beneficial Effects ◽  
Significant Difference ◽  
Relative Absorption ◽  
Β Carotene

Carotenoids have been shown to have potential beneficial effects on human health which has led to an increasing interest in the study of their bioavailability. A Caco-2 cell model, as previously described, was employed to examine the percentage transfer of the carotenoids α-carotene, β-carotene, lycopene, astaxanthin, β-cryptoxanthin, lutein and zeaxanthin through an intact, highly differentiated Caco-2 cell monolayer at a range of different amounts. Our results show that astaxanthin, a carotenoid with powerful antioxidant capacity, had the highest percentage transfer overall. We examined the cellular uptake and secretion of lutein and zeaxanthin to compare two structurally similar carotenoids. Both were efficiently transported through the monolayer with a range between 5·1 (sem 1·2) % to 20·2 (sem 3·3) % and 5·5 (sem 2·5) % to 13·4 (sem 4) % for lutein and zeaxanthin, respectively. These carotenoids were compared to each other at each added amount and no significant difference was observed between the two xanthophylls. The carotene carotenoids α-carotene, β-carotene and lycopene and the xanthophyll β-cryptoxanthin were also examined and had lower uptake and secretion values when compared to lutein, zeaxanthin and astaxanthin. The xanthophyll β-cryptoxanthin was also not significantly different when compared to the carotene carotenoids. Data generated from this study compares well with in vivo bioavailability studies. Furthermore, the model provides comparative data on the relative absorption and transfer of seven different carotenoids. Our data indicate that lower amounts of carotenoids were absorbed and transferred more efficiently than higher amounts suggesting a saturation effect at higher exposure.

Search for Compounds Suppressing Intestinal α-Glucosidase Expression in Caco-2 Cells

2019 ◽  
Vol 2 (2) ◽  
pp. 96-101
Author(s):  
Kota Noda ◽  
Eisuke Kato ◽  
Jun Kawabata
Keyword(s):  
Blood Glucose ◽  
Intestinal Tract ◽  
Cell Model ◽  
Epigallocatechin Gallate ◽  
Calluna Vulgaris ◽  
Active Principle ◽  
Intestinal Epithelial ◽  
Mrna Expression Level ◽  
Epicatechin Gallate ◽  
Control Post

Diabetes is a chronic disease characterized by elevated blood glucose level.Reducing carbohydrate absorption from the intestinal tract is an effective strategy to control post-meal blood glucose level. Inhibition of intestinal α-glucosidase, involved in digestion of carbohydrates, is known as an approach to accomplish this. On the other hand, reduction of α-glucosidase amount is expected to work in the similar manner. However, none of the previousstudy pursues this approach. A convenient assay was developed to evaluate α-glucosidase amount employing Caco-2 cells, the intestinal epithelial cell model reported to express α-glucosidase. Sixty plants were screened and two candidate plants, Calluna vulgaris and Perilla frutescens var. crispa were found to reduce α-glucosidase expression. C. vulgaris extract was subjected to activity guided isolation. Proanthocyanidin was identified as the active principle which was analyzed by thiol decomposition to reveal the components as a mixture ofcatechin, epicatechin, epigallocatechin, and A type procyanidin dimer. The proanthocyanidin suppressed about 30% of α-glucosidase amount evaluated through convenient assay, and suppressed bulk of mRNA expression level of sucrase-isomaltase (SI) at 0.125 mg/mL. Several flavan-3-ol monomers were also tested, and epicatechin gallate and epigallocatechin gallate were found to suppress α-glucosidase amount significantly.

Improved micro-impedance spectroscopy to determine cell barrier properties

2020 ◽  
Vol 4 (3) ◽  
pp. 150-155 ◽  
Author(s):  
Md. Mehadi Hasan Sohag ◽  
Olivier Nicoud ◽  
Racha Amine ◽  
Abir Khalil-Mgharbel ◽  
Jean-Pierre Alcaraz ◽  
...  
Keyword(s):  
Impedance Spectroscopy ◽  
Epithelial Cells ◽  
Lipid Bilayers ◽  
Cultured Cells ◽  
Cell Model ◽  
Measurement Techniques ◽  
Cell Monolayer ◽  
Microfluidic Channel ◽  
Small Surface ◽  
Resistance Pathway

AbstractThe goal of this study was to determine whether the Tethapod system, which was designed to determine the impedance properties of lipid bilayers, could be used for cell culture in order to utilise micro-impedance spectroscopy to examine further biological applications. To that purpose we have used normal epithelial cells from kidney (RPTEC) and a kidney cancer cell model (786-O). We demonstrate that the Tethapod system is compatible with the culture of 10,000 cells seeded to grow on a small area gold measurement electrode for several days without affecting the cell viability. Furthermore, the range of frequencies for EIS measurements were tuned to examine easily the characteristics of the cell monolayer. We demonstrate significant differences in the paracellular resistance pathway between normal and cancer kidney epithelial cells. Thus, we conclude that this device has advantages for the study of cultured cells that include (i) the configuration of measurement and reference electrodes across a microfluidic channel, and (ii) the small surface area of 6 parallel measurement electrodes (2.1 mm2) integrated in a microfluidic system. These characteristics might improve micro-impedance spectroscopy measurement techniques to provide a simple tool for further studies in the field of the patho-physiology of biological barriers.

Permeability to albumin in isolated coronary venules

1993 ◽  
Vol 265 (2) ◽  
pp. H543-H552 ◽  
Author(s):  
Y. Yuan ◽  
W. M. Chilian ◽  
H. J. Granger ◽  
D. C. Zawieja
Keyword(s):  
Permeability Coefficient ◽  
Filtration Rate ◽  
Intraluminal Pressure ◽  
Apparent Permeability ◽  
Filtration Pressure ◽  
Diffusive Permeability ◽  
Apparent Permeability Coefficient ◽  
Chemical Conditions ◽  
Physical And Chemical ◽  
Intravascular Pressure

This study reports measurements of albumin permeability in isolated coronary venules. The isolated microvessel technique allows the quantification of transmural exchange of macromolecules under tightly controlled physical and chemical conditions. Transvenular exchange of albumin was studied in isolated coronary venules during alterations in filtration rate caused by changes in intravascular pressure. The apparent permeability coefficient of albumin (Pa) at an intraluminal pressure of 11 cmH2O was 3.92 +/- 0.43 x 10(-6) cm/s. Elevating intraluminal pressure to 16 and 21 cmH2O increased Pa to 5.13 +/- 0.57 x 10(-6) and 6.78 +/- 0.66 x 10(-6) cm/s, respectively. Calculation of the true diffusive permeability coefficient of albumin (Pd) at zero filtration rate was 1.54 x 10(-6) cm/s. The product of hydraulic conductance (Lp) and (1 - sigma), where sigma is the solute reflection coefficient, was 3.25 x 10(-7) cm.s-1 x cmH2O-1. At a net filtration pressure of 4-5 cmH2O, diffusion accounts for > 60% of total albumin transport across the venular wall. Transmural albumin flux is very sensitive to filtration rate, rising 6.7% for each cmH2O elevation of net filtration pressure. At 11 cmH2O net filtration pressure, convection accounts for nearly 70% of net albumin extravasation from the venular lumen. We suggest that the isolated coronary venule is a suitable preparation for the study of solute exchange in the heart.

scholarly journals Protective Role of Natural and Semi-Synthetic Tocopherols on TNFα-Induced ROS Production and ICAM-1 and Cl-2 Expression in HT29 Intestinal Epithelial Cells

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 160
Author(s):  
Vladana Domazetovic ◽  
Irene Falsetti ◽  
Caterina Viglianisi ◽  
Kristian Vasa ◽  
Cinzia Aurilia ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Properties ◽  
Intestinal Barrier ◽  
Protective Role ◽  
Intercellular Adhesion Molecule ◽  
Intestinal Epithelial ◽  
Intercellular Adhesion Molecule 1 ◽  
Beneficial Effects ◽  
Bowel Diseases

Vitamin E, a fat-soluble compound, possesses both antioxidant and non-antioxidant properties. In this study we evaluated, in intestinal HT29 cells, the role of natural tocopherols, α-Toc and δ-Toc, and two semi-synthetic derivatives, namely bis-δ-Toc sulfide (δ-Toc)2S and bis-δ-Toc disulfide (δ-Toc)2S2, on TNFα-induced oxidative stress, and intercellular adhesion molecule-1 (ICAM-1) and claudin-2 (Cl-2) expression. The role of tocopherols was compared to that of N-acetylcysteine (NAC), an antioxidant precursor of glutathione synthesis. The results show that all tocopherol containing derivatives used, prevented TNFα-induced oxidative stress and the increase of ICAM-1 and Cl-2 expression, and that (δ-Toc)2S and (δ-Toc)2S2 are more effective than δ-Toc and α-Toc. The beneficial effects demonstrated were due to tocopherol antioxidant properties, but suppression of TNFα-induced Cl-2 expression seems not only to be related with antioxidant ability. Indeed, while ICAM-1 expression is strongly related to the intracellular redox state, Cl-2 expression is TNFα-up-regulated by both redox and non-redox dependent mechanisms. Since ICAM-1 and Cl-2 increase intestinal bowel diseases, and cause excessive recruitment of immune cells and alteration of the intestinal barrier, natural and, above all, semi-synthetic tocopherols may have a potential role as a therapeutic support against intestinal chronic inflammation, in which TNFα represents an important proinflammatory mediator.

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