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 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 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.

On the mechanism of luminal CO2 generation during jejunal bicarbonate absorption

1984 ◽  
Vol 246 (6) ◽  
pp. G687-G694
Author(s):  
G. M. Feldman ◽  
M. A. Arnold ◽  
A. N. Charney
Keyword(s):  
Jejunal Mucosa ◽  
Sprague Dawley ◽  
Apparent Permeability ◽  
Co2 Gas ◽  
Arterial Pco2 ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
Apparent Permeability Coefficient

The mechanism of the increase in luminal CO2 tension (PCO2) that accompanies jejunal HCO-3 absorption is unknown. One possibility is that mucosal metabolism and the reaction of absorbed HCO-3 with blood buffers in mucosal capillaries govern luminal PCO2. To evaluate this possibility, jejunal segments of anesthetized adult male Sprague-Dawley rats were perfused in vivo with modified Ringer solutions with varying PCO2 levels (0-141 mmHg). Arterial PCO2 was varied by mechanical ventilation (20-70 mmHg). The net flux of CO2 gas into bulk luminal fluid varied directly with the transmucosal PCO2 gradient both in the absence (r = 0.98, P less than 0.001) and presence of net HCO-3 absorption (r = 0.97, P less than 0.001). The apparent permeability coefficient for CO2 gas across the jejunal mucosa was relatively low (2 X 10(-4) cm3 X s-1 X cm length -1) and was not affected by net HCO-3 absorption. Under conditions of equal arterial blood and perfusate PCO2 levels (40 mmHg), the PCO2 in mucosa and effluent was 51 and 44 mmHg, respectively, in the absence and 62 and 48 mmHg, respectively, in the presence of net HCO-3 absorption. These results suggest that CO2 diffuses from the mucosal region into bulk liminal fluid during net HCO-3 absorption in the rat jejunum. In addition, we found in vitro that the elevation of mucosal PCO2 above arterial PCO2 during net HCO-3 absorption can be quantitatively accounted for by metabolism and the admixture of absorbed HCO-3 with blood buffers.

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.

scholarly journals Possible Role of P-Glycoprotein in Cyclosporine -Acitretin Drug Interaction

2019 ◽  
Vol 1 (4) ◽  
Author(s):  
Subhashri Shrihari Rajendran ◽  
Vimalavathini Ramesh
Keyword(s):  
Drug Interaction ◽  
Ex Vivo ◽  
Research Work ◽  
Close Monitoring ◽  
Dependent Manner ◽  
Apparent Permeability ◽  
P Glycoprotein ◽  
Apparent Permeability Coefficient

P-glycoprotein, an efflux transporter prevents intracellular accumulation of xenobiotics. Cyclosporine A and acitretin are used to treat psoriasis. The present research work aims to investigate the possible role of P-glycoprotein in Cyclosporine- Acitretin drug interaction due to evidence of both drugs having affinity for P-glycoprotein.The study has three different objective namely to assess apparent permeability coefficient of cyclosporine in presence of acitretin by non-everted sac technique, to study the intestinal permeation and absorption kinetics of cyclosporine in presence of acitretin by single pass intestinal perfusion (SPIP) technique and to study the influence of acitretin on oral bioavailability of cyclosporine in Wistar rats.The result of ex vivo, in situ and in vivo study showed that cyclosporine level increased in a time dependent manner. As the dose of acitretin increases the cyclosporine concentration in all three methods tend to increase and was statistically significant. The improvement in absorption of cyclosporine may be due to the inhibition of P-glycoprotein transporter in the intestine by acitretin. Thus acitretin may enhance the oral pharmacokinetics of cyclosporine. Hence this combination may require close monitoring for better therapeutic outcome. Our study confirmed the inhibitory role of acitretin on P-glycoprotein leading to increase concentration of cyclosporine.

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 Absorption and Intestinal Metabolic Profile of Oleocanthal in Rats

Pharmaceutics ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 134 ◽  
Author(s):  
López-Yerena ◽  
Vallverdú-Queralt ◽  
Mols ◽  
Augustijns ◽  
Lamuela-Raventós ◽  
...  
Keyword(s):  
Permeability Coefficient ◽  
Oral Absorption ◽  
Virgin Olive Oil ◽  
Extra Virgin Olive Oil ◽  
Rat Plasma ◽  
Apparent Permeability ◽  
Time Curve ◽  
In Situ Perfusion ◽  
Apparent Permeability Coefficient

Oleocanthal (OLC), a phenolic compound of extra virgin olive oil (EVOO), has emerged as a potential therapeutic agent against a variety of diseases due to its anti-inflammatory activity. The aim of the present study is to explore its in vivo intestinal absorption and metabolism. An in situ perfusion technique in rats was used, involving simultaneous sampling from the luminal perfusate and mesenteric blood. Samples were analysed by UHPLC–MS–MS for the presence of oleocanthal (OLC) and its metabolites. OLC was mostly metabolized by phase I metabolism, undergoing hydration, hydrogenation and hydroxylation. Phase II reactions (glucuronidation of hydrogenated OLC and hydrated metabolites) were observed in plasma samples. OLC was poorly absorbed in the intestine, as indicated by the low effective permeability coefficient (2.23 ± 3.16 × 10−5 cm/s) and apparent permeability coefficient (4.12 ± 2.33 × 10−6 cm/s) obtained relative to the values of the highly permeable reference compound levofloxacin (LEV). The extent of OLC absorption reflected by the area under the mesenteric blood-time curve normalized by the inlet concentration (AUC) was also lower than that of LEV (0.25 ± 0.04 vs. 0.64 ± 0.03, respectively). These results, together with the observed intestinal metabolism, suggest that OLC has a moderate-to-low oral absorption; but higher levels of OLC are expected to reach human plasma vs. rat plasma.

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.

scholarly journals Ubisol-Q10, a Nanomicellar and Water-Dispersible Formulation of Coenzyme-Q10 as a Potential Treatment for Alzheimer’s and Parkinson’s Disease

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 764
Author(s):  
Darcy Wear ◽  
Caleb Vegh ◽  
Jagdeep K. Sandhu ◽  
Marianna Sikorska ◽  
Jerome Cohen ◽  
...  
Keyword(s):  
Coenzyme Q10 ◽  
Water Soluble ◽  
In Vivo Models ◽  
Federal Drug Administration ◽  
Water Dispersible ◽  
Therapeutic Value ◽  
Effective Doses ◽  
First Time

The world continues a desperate search for therapies that could bring hope and relief to millions suffering from progressive neurodegenerative diseases such as Alzheimer’s (AD) and Parkinson’s (PD). With oxidative stress thought to be a core stressor, interests have long been focused on applying redox therapies including coenzyme-Q10. Therapeutic use has failed to show efficacy in human clinical trials due to poor bioavailability of this lipophilic compound. A nanomicellar, water-dispersible formulation of coenzyme-Q10, Ubisol-Q10, has been developed by combining coenzyme-Q10 with an amphiphilic, self-emulsifying molecule of polyoxyethanyl α-tocopheryl sebacate (derivatized vitamin E). This discovery made possible, for the first time, a proper assessment of the true therapeutic value of coenzyme-Q10. Micromolar concentrations of Ubisol-Q10 show unprecedented neuroprotection against neurotoxin exposure in in vitro and in vivo models of neurodegeneration and was extremely effective when delivered either prior to, at the time of, and most significantly, post-neurotoxin exposure. These findings indicate a possible way forward for clinical development due to effective doses well within Federal Drug Administration guidelines. Ubisol-Q10 is a potent mobilizer of astroglia, antioxidant, senescence preventer, autophagy activator, anti-inflammatory, and mitochondrial stabilizer. Here we summarize the work with oil-soluble coenzyme-Q10, its limitations, and focus mainly on efficacy of water-soluble coenzyme-Q10 in neurodegeneration.

Endogenous hydrogen sulfide sulfhydrates IKKβ at cysteine 179 to control pulmonary artery endothelial cell inflammation

2019 ◽  
Vol 133 (20) ◽  
pp. 2045-2059 ◽  
Author(s):  
Da Zhang ◽  
Xiuli Wang ◽  
Siyao Chen ◽  
Selena Chen ◽  
Wen Yu ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Endothelial Cell ◽  
Pulmonary Artery ◽  
Cell Model ◽  
Site Directed Mutagenesis ◽  
Critical Event ◽  
Hypertensive Rats ◽  
Pulmonary Artery Endothelial Cell

Abstract Background: Pulmonary artery endothelial cell (PAEC) inflammation is a critical event in the development of pulmonary arterial hypertension (PAH). However, the pathogenesis of PAEC inflammation remains unclear. Methods: Purified recombinant human inhibitor of κB kinase subunit β (IKKβ) protein, human PAECs and monocrotaline-induced pulmonary hypertensive rats were employed in the study. Site-directed mutagenesis, gene knockdown or overexpression were conducted to manipulate the expression or activity of a target protein. Results: We showed that hydrogen sulfide (H2S) inhibited IKKβ activation in the cell model of human PAEC inflammation induced by monocrotaline pyrrole-stimulation or knockdown of cystathionine γ-lyase (CSE), an H2S generating enzyme. Mechanistically, H2S was proved to inhibit IKKβ activity directly via sulfhydrating IKKβ at cysteinyl residue 179 (C179) in purified recombinant IKKβ protein in vitro, whereas thiol reductant dithiothreitol (DTT) reversed H2S-induced IKKβ inactivation. Furthermore, to demonstrate the significance of IKKβ sulfhydration by H2S in the development of PAEC inflammation, we mutated C179 to serine (C179S) in IKKβ. In purified IKKβ protein, C179S mutation of IKKβ abolished H2S-induced IKKβ sulfhydration and the subsequent IKKβ inactivation. In human PAECs, C179S mutation of IKKβ blocked H2S-inhibited IKKβ activation and PAEC inflammatory response. In pulmonary hypertensive rats, C179S mutation of IKKβ abolished the inhibitory effect of H2S on IKKβ activation and pulmonary vascular inflammation and remodeling. Conclusion: Collectively, our in vivo and in vitro findings demonstrated, for the first time, that endogenous H2S directly inactivated IKKβ via sulfhydrating IKKβ at Cys179 to inhibit nuclear factor-κB (NF-κB) pathway activation and thereby control PAEC inflammation in PAH.

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