In vitro and in situ study on characterizationand mechanismofthe intestinal absorptionof 2,3,5,4'-tetrahydroxy-stilbene-2-O-β-D-glucoside

Abstract Background: 2,3,5,4'-tetrahydroxystilbence-2-O-β-D-glucoside(TSG) is a polyhydroxyphenolic compound, which exhibited a broad spectrum of pharmacological activities, such asanti-inflammatory, anti-depression, anti-oxidation and anti-atherosclerosis.However, the compound had poor bioavailability and the underlying absorption mechanisms had not been studied. Therefore, the purpose of this study was to investigate the intestinal absorption mechanism of TSG. Methods: This study used Caco-2 cell monolayer model and single-passintestinal perfusion modelto explore the gastrointestinal absorption mechanisms of TSG. The effects of basic parameters such as drug concentration, time and pH on the intestinal absorption of TSG were analyzed by high performance liquid chromatography.The absorption susceptibility of TSG to three inhibitors, P-gp inhibitors verapamil hydrochloride and quinidine, and MRP2 inhibitor probenecid were also assessed. Results: TSG was poorly absorbed in the intestines and the absorption of TSG in stomach is much higher than that in intestine. Both in vitro and in situ experiments showed that the absorption of TSG was saturated with increasing concentration and it was better absorbed in a weakly acidic environment pH 6.4. Moreover, TSG interacts with P-gp and MRP2, and TSG was not only the substrate of the P-gp and MRP2, but also affected the expression of P-gp and MRP2. Conclusions: It wasconcluded that the gastrointestinalabsorption mechanisms ofTSG involved processes passive transport and the participation ofefflux transporters.

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In vitro and in situ study on characterizationand mechanismofthe intestinal absorptionof 2,3,5,4'-tetrahydroxy-stilbene-2-O-β-D-glucoside

10.21203/rs.2.15497/v2 ◽

2019 ◽

Author(s):

Cheng Wang ◽

Yimeng Zhou ◽

Xiaohong Gong ◽

Li Zheng ◽

Yunxia Li

Keyword(s):

Intestinal Absorption ◽

High Performance ◽

Cell Monolayer ◽

Absorption Mechanism ◽

Pharmacological Activities ◽

In Situ Study ◽

Concentration Time ◽

Basic Parameters

Abstract Background: 2,3,5,4'-tetrahydroxystilbence-2-O-β-D-glucoside(TSG) is a polyhydroxyphenolic compound, which exhibited a broad spectrum of pharmacological activities, such asanti-inflammatory, anti-depression, anti-oxidation and anti-atherosclerosis.However, the compound had poor bioavailability and the underlying absorption mechanisms had not been studied. Therefore, the purpose of this study was to investigate the intestinal absorption mechanism of TSG. Methods:This study used Caco-2 cell monolayer model and single-passintestinal perfusion modelto explore the gastrointestinal absorption mechanisms of TSG. The effects of basic parameters such as drug concentration, time and pH on the intestinal absorption of TSG were analyzed by high performance liquid chromatography.The absorption susceptibility of TSG to three inhibitors, P-gp inhibitors verapamil hydrochloride and quinidine, and MRP2 inhibitor probenecid were also assessed. Results: TSG was poorly absorbed in the intestines and the absorption of TSG in stomach is much higher than that in intestine. Both in vitro andin situ experiments showed that the absorption of TSG was saturated with increasing concentration and it was better absorbed in a weakly acidic environment pH 6.4. Moreover, TSG interacts with P-gp and MRP2, and TSG was not only the substrate of the P-gp and MRP2, but also affected the expression of P-gp and MRP2. Conclusions: It wasconcluded that the gastrointestinalabsorption mechanisms ofTSG involved processes passive transport and the participation ofefflux transporters.

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In vivo and in vitro study on characterization and mechanism of the intestinal absorption of 2,3,5,4'-tetrahydroxy-stilbene-2-O-β-D-glucoside

10.21203/rs.2.15497/v1 ◽

2019 ◽

Author(s):

Cheng Wang ◽

Yimeng Zhou ◽

Xiaohong Gong ◽

Li Zheng ◽

Yunxia Li

Keyword(s):

Intestinal Absorption ◽

High Performance ◽

Cell Monolayer ◽

In Vitro Study ◽

Absorption Mechanism ◽

Pharmacological Activities ◽

Concentration Time ◽

Basic Parameters

Abstract Background: 2,3,5,4'-tetrahydroxystilbence-2-O-β-D-glucoside(TSG) is a polyhydroxyphenolic compound, which exhibits a broad spectrum of pharmacological activities, such asanti-inflammatory, anti-depression, anti-oxidation and anti-atherosclerosis.However, the compound has poor bioavailability and the underlying absorption mechanisms has not been studied. Therefore, the purpose of this study was to investigate the intestinal absorption mechanism of TSG. Methods: This study used the Caco-2 cell monolayer model and the single-passintestinal perfusion modelto explore the intestinal absorption mechanisms of TSG. The effects of basic parameters such as drug concentration, time and pH on the intestinal absorption of TSG were analyzed by high performance liquid chromatography.In addition, the susceptibility of TSG absorption process to treatment with three inhibitors, such as P-gp inhibitors verapamil hydrochloride and quinidine, and the MRP2 inhibitor probenecid were also assessed. Results: TSG is poorly absorbed in the intestines and the absorption of TSG in the stomach is much higher than that in the intestine. Both in vivo and in vitro experiments showed that the absorption of TSG was saturated with increasing concentration. and it was better absorbed in a weakly acidic environment with a pH of 6.4. Moreover, TSG interacts with P-gp and MRP2, and TSG is not only the substrate of the P-gp and MRP2, but also affects the expression of P-gp and MRP2. Conclusions: It can be concluded that the intestinal absorption mechanismsofTSG involve processes passive transport and the participation of efflux transporters.

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In Silico Assessment of ADME Properties: Advances in Caco-2 Cell Monolayer Permeability Modeling

Current Topics in Medicinal Chemistry ◽

10.2174/1568026619666181130140350 ◽

2019 ◽

Vol 18 (26) ◽

pp. 2209-2229 ◽

Cited By ~ 4

Author(s):

Hai Pham-The ◽

Miguel Á. Cabrera-Pérez ◽

Nguyen-Hai Nam ◽

Juan A. Castillo-Garit ◽

Bakhtiyor Rasulev ◽

...

Keyword(s):

Intestinal Absorption ◽

In Silico ◽

Review Paper ◽

Cell Monolayer ◽

Cell Permeability ◽

Drug Substances ◽

Wide Range ◽

Modeling Techniques

One of the main goals of in silico Caco-2 cell permeability models is to identify those drug substances with high intestinal absorption in human (HIA). For more than a decade, several in silico Caco-2 models have been made, applying a wide range of modeling techniques; nevertheless, their capacity for intestinal absorption extrapolation is still doubtful. There are three main problems related to the modest capacity of obtained models, including the existence of inter- and/or intra-laboratory variability of recollected data, the influence of the metabolism mechanism, and the inconsistent in vitro-in vivo correlation (IVIVC) of Caco-2 cell permeability. This review paper intends to sum up the recent advances and limitations of current modeling approaches, and revealed some possible solutions to improve the applicability of in silico Caco-2 permeability models for absorption property profiling, taking into account the above-mentioned issues.

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New In Vitro Coculture Model for Evaluating Intestinal Absorption of Different Lipid Nanocapsules

Pharmaceutics ◽

10.3390/pharmaceutics13050595 ◽

2021 ◽

Vol 13 (5) ◽

pp. 595

Author(s):

Norraseth Kaeokhamloed ◽

Emillie Roger ◽

Jérôme Béjaud ◽

Nolwenn Lautram ◽

Florence Manero ◽

...

Keyword(s):

Surface Modification ◽

Intestinal Absorption ◽

Oral Absorption ◽

Membrane Integrity ◽

Microvascular Endothelial Cell ◽

Absorption Mechanism ◽

Apparent Permeability ◽

Lipid Nanocapsules ◽

Coculture Model

Standard models used for evaluating the absorption of nanoparticles like Caco-2 ignore the presence of vascular endothelium, which is a part of the intestinal multi-layered barrier structure. Therefore, a coculture between the Caco-2 epithelium and HMEC-1 (Human Microvascular Endothelial Cell type 1) on a Transwell® insert has been developed. The model has been validated for (a) membrane morphology by transmission electron microscope (TEM); (b) ZO-1 and β-catenin expression by immunoassay; (c) membrane integrity by trans-epithelial electrical resistance (TEER) measurement; and (d) apparent permeability of drugs from different biopharmaceutical classification system (BCS) classes. Lipid nanocapsules (LNCs) were formulated with different sizes (55 and 85 nm) and surface modifications (DSPE-mPEG (2000) and stearylamine). Nanocapsule integrity and particle concentration were monitored using the Förster resonance energy transfer (FRET) technique. The result showed that surface modification by DSPE-mPEG (2000) increased the absorption of 55-nm LNCs in the coculture model but not in the Caco-2. Summarily, the coculture model was validated as a tool for evaluating the intestinal absorption of drugs and nanoparticles. The new coculture model has a different LNCs absorption mechanism suggesting the importance of intestinal endothelium and reveals that the surface modification of LNCs can modify the in vitro oral absorption.

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Comparison of the intestinal absorption and bioavailability of γ-tocotrienol and α-tocopherol: in vitro, in situ and in vivo studies

Biopharmaceutics & Drug Disposition ◽

10.1002/bdd.1790 ◽

2012 ◽

Vol 33 (5) ◽

pp. 246-256 ◽

Cited By ~ 30

Author(s):

Bilal S. Abuasal ◽

Hisham Qosa ◽

Paul W. Sylvester ◽

Amal Kaddoumi

Keyword(s):

Intestinal Absorption ◽

In Vivo Studies

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ANG II modifies cardiomyocyte function via extracardiac and intracardiac neurons: in situ and in vitro studies

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1997.272.3.r766 ◽

1997 ◽

Vol 272 (3) ◽

pp. R766-R775 ◽

Cited By ~ 6

Author(s):

M. Horackova ◽

J. A. Armour

Keyword(s):

Guinea Pig ◽

Receptor Antagonist ◽

Neuronal Activity ◽

Ang Ii ◽

Arterial Blood ◽

Cardiac Ganglia ◽

In Situ Experiments ◽

Anesthetized Dogs

To determine whether angiotensin II (ANG II) affects cardiac performance via neurons in intrathoracic cardiac ganglia, studies were performed on anesthetized dogs. To exclude possible vascular regulatory effects of ANG II, experiments were also performed using long-term cultures of adult guinea pig ventricular cardiomyocytes with or without intrathoracic neurons. 1) In in situ experiments in 10 anesthetized dogs, cardiac augmentation occurred when ANG II (10 microl or 0.1 ml; 10-100 microM) was administered into limited loci within acutely decentralized stellate or middle cervical ganglia that were neurally connected to, but not those disconnected from, the heart. In another 18 dogs, ANG II increased intrinsic cardiac neuronal activity when administered adjacent to such neurons or into their local arterial blood supply. Ventricular ionotropic effects elicited by ANG II were eliminated by timolol, whereas increases in intrinsic cardiac neuronal activity were not affected. Effects elicited by ANG II were eliminated by administration of a selective AT1 receptor antagonist (losartan) but not by a selective AT2 receptor antagonist (PD-123319). 2) In in vitro experiments, ANG II (100 nM) induced positive chronotropic effects on cultured adult guinea pig cardiomyocytes innervated with adult extrinsic or intrinsic cardiac neurons, but not those cultured without neurons. The frequency of calcium inward current (Ca(i)) transients (recorded by fura 2 fluorescence) increased in innervated cocultures but not in the noninnervated cardiomyocyte cultures; however, the amplitude of Ca(i) transients was not affected by ANG II in cultures or in freshly isolated adult guinea pig cardiomyocytes. ANG II-induced effects in cocultures were blocked by losartan but not PD-123319 or timolol. Thus 1) ANG II-sensitive neurons exist in intrathoracic extracardiac and intrinsic cardiac ganglia; 2) these neurons possess AT1 receptors; and 3) these neurons appear to act directly and indirectly via adrenergic neurons to enhance cardiomyocyte function.

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Electrical impedance measurement system to assess in-situ experiments on epithelia under ELF magnetic fields exposure

Journal of Applied Research and Technology ◽

10.22201/icat.24486736e.2021.19.3.1693 ◽

2021 ◽

Vol 19 (3) ◽

pp. 217-226

Author(s):

G. Domínguez ◽

E. Cardiel ◽

J.L Reyes ◽

E. Sánchez ◽

P.R. Hernández

Keyword(s):

Impedance Spectroscopy ◽

Magnetic Fields ◽

Cell Cultures ◽

Electrical Impedance ◽

Controlled Environment ◽

Spectroscopy Technique ◽

In Situ Experiments ◽

Impedance Spectroscopy Technique

Purpose: The development of an electric impedance meter based on the impedance spectroscopy technique, for in vitro and in situ experimentation, with cellular epithelia submitted to extremely low frequency magnetic fields in a controlled environment. Unlike other reported systems, a strength of the one presented here is that it avoids the influence of external factors on the experiment. Materials and methods: The designed system employs the electrical impedance values obtained by the impedance spectroscopy technique to determine the parameters of the simple equivalent electrical model of a cellular monolayer. The Madin-Darby Canine Kidney (MDCK) cell cultures were used as subjects of study in the experimental protocol. Results: The validation was carried out by comparing the transepithelial electrical impedance data of the cell cultures obtained with the developed system and those of the Cellzscope® commercial system used as the standard. Non-significant differences were obtained. Conclusion: It was confirmed that the developed system provides reliable values of transepithelial electrical impedance to experiment with cell cultures and take advantage of the controlled environment to reduce the effects of experimental management.

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Agrobiological Interactions of Essential Oils of Two Menthol Mints: Mentha piperita and Mentha arvensis

Molecules ◽

10.3390/molecules25010059 ◽

2019 ◽

Vol 25 (1) ◽

pp. 59 ◽

Cited By ~ 2

Author(s):

Danuta Kalemba ◽

Agnieszka Synowiec

Keyword(s):

Biological Activities ◽

Review Article ◽

Mentha Piperita ◽

Agricultural Pest ◽

Mentha Arvensis ◽

Botanical Pesticides ◽

New Methods ◽

In Situ Experiments

This review article discusses the active constituents and potential of two menthol mint oils, Mentha piperita (MPEO) and Mentha arvensis (MAEO), as natural sources for botanical pesticides. The biological activities of these menthol mint oils, which can be useful in agriculture, have been broadly researched, especially toward phytotoxic microorganisms. To a lesser extent, the insecticidal and herbicidal activities of mint EOs have also been studied. It is apparent that the prospect of using menthol mint oils in agriculture is increasing in popularity. A number of investigations showed that the in vitro efficacy of MPEO and MAEO, as well as that of their main constituent, menthol, is pronounced. The results of in vitro research are useful for choosing EOs for further investigations. However, it is clear that in situ experiments are crucial and should be more extensively developed. At the same time, known techniques are to be applied to this area and new methods should be worked out, aiming at the improvement of EOs’ pesticidal efficacy and cost-effectiveness, for future implementation in agricultural pest control.

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