Caco-2 Cell Transport Research Articles

Effect of pasteurization and storage on the bioavailability of milk proteins during in vitro intestinal digestion and Caco-2 cell transport

This study fills a specific knowledge gap by comprehensively investigating the intestinal digestive dynamics and transport kinetics of pasteurized milk proteins during cold storage, utilizing dynamic in vitro digestion models, human colorectal adenocarcinoma cell line (Caco-2) transport simulations, peptideomics and amino acid analysis. The content of free amino acids during intestinal digestion and their transport capacity (excluding lysine) were highest in pasteurized milk stored for 7 days (PAST-D7), intermediate in pasteurized milk stored for 0 days (PAST-D0) and lowest in raw milk (RM). Conversely, the quantity and intensity of bioactive peptides during digestion decreased with pasteurization and storage. Additionally, pasteurization and storage reduced the intensity of bioactive peptides transported through Caco-2 cells and the types and intensity of potential allergenic peptides. These findings indicate that while pasteurization and storage may diminish some physiological benefits of milk, they may also enhance protein bioavailability and reduce allergenicity.

Zn2+ chelating peptide GFLGSP: Characterization of structure/Zn2+ chelating mode and the potential mechanisms for promoting Zn2+ transport in Caco-2 cells

This study focused on exploring the Zn2+ chelating peptide GFLGSP: the characterization of structure/Zn2+ chelating mode and the potential mechanisms for promoting Zn2+ transport in Caco-2 cells. The findings revealed the bidentate chelating between Zn2+ and carboxyl oxygen atom in Pro6 residue. Thereafter, the secondary structure of GFLGSP remained unchanged, but there was an increase in zeta potential and particle size. Notably, the GFLGSP-Zn2+ complex enhanced the Zn2+ transport rate and modulated ZIP4 and ZNT1 expression in a Caco-2 cells monolayer model. As revealed by molecular docking analysis, GFLGSP interacted with ZIP4 through intermolecular hydrogen bonds as well as Van der Waals forces. The Zn2+ transport mechanisms of the GFLGSP-Zn2+ complex encompassed ZIP4 (vital channel), endocytosis (primary pathway) and paracellular transport (supplementary pathway). Based on these results, the tilapia skin collagen-derived GFLGSP hold promise as the potential dietary Zn2+ supplement.

Interactions between corn starch and lingonberry polyphenols and their effects on starch digestion and glucose transport

This study investigated the interaction mechanism between corn starch (CS) and lingonberry polyphenols (LBP) during starch gelatinization, focusing on their effects on starch structure and physicochemical properties. Moreover, it explored the effect of this interaction on starch digestion and glucose transport. The results indicated that LBP interacted non-covalently with CS during starch gelatinization, disrupted the short-range ordered structure of starch, decreased gelatinization enthalpy of starch, and formed a dense network structure. Furthermore, the incorporation of LBP remarkably reduced the digestibility of CS. In particular, the addition of 10 % LBP decreased the terminal digestibility (C∞) from 77.87 % to 60.43 % and increased the amount of resistant starch (RS) by 21.63 %. LBP was found to inhibit α-amylase and α-glucosidase in a mixed manner. Additionally, LBP inhibited glucose transport in Caco-2 cells following starch digestion. When 10 % LBP was added, there was a 34.17 % decrease in glucose transport compared with starch digestion without LBP. This study helps establish the foundation for the development of LBP-containing starch or starch-based healthy foods and provides new insights into the mechanism by which LBP lowers blood glucose.

Metabolomic insights into the profile, bioaccessibility, and transepithelial transport of polyphenols from germinated quinoa during in vitro gastrointestinal digestion/Caco-2 cell transport, and their prebiotic effects during colonic fermentation

The health-promoting activities of polyphenols and their metabolites originating from germinated quinoa (GQ) are closely related to their digestive behavior, absorption, and colonic fermentation; however, limited knowledge regarding these properties hinder further development. The aim of this study was to provide metabolomic insights into the profile, bioaccessibility, and transepithelial transport of polyphenols from germinated quinoa during in vitro gastrointestinal digestion and Caco-2 cell transport, whilst also investigating the changes in the major polyphenol metabolites and the effects of prebiotics during colonic fermentation. It was found that germination treatment increased the polyphenol content of quinoa by 21.91%. Compared with RQ group, 23 phenolic differential metabolites were upregulated and 47 phenolic differential metabolites were downregulated in GQ group. Compared with RQ group after simulated digestion, 7 kinds of phenolic differential metabolites were upregulated and 17 kinds of phenolic differential metabolites were downregulated in GQ group. Compared with RQ group after cell transport, 7 kinds of phenolic differential metabolites were upregulated and 9 kinds of phenolic differential metabolites were downregulated in GQ group. In addition, GQ improved the bioaccessibilities and transport rates of various polyphenol metabolites. During colonic fermentation, GQ group can also increase the content of SCFAs, reduce pH value, and adjust gut microbial populations by increasing the abundance of Actinobacteria, Bacteroidetes, Verrucomicrobiota, and Spirochaeota at the phylum level, as well as Bifidobacterium, Megamonas, Bifidobacterium, Brevundimonas, and Bacteroides at the genus level. Furthermore, the GQ have significantly inhibited the activity of α-amylase and α-glucosidase. Based on these results, it was possible to elucidate the underlying mechanisms of polyphenol metabolism in GQ and highlight its beneficial effects on the gut microbiota.

Digestion of surfactants does not affect their ability to inhibit P-gp-mediated transport in vitro

While various non-ionic surfactants at low concentrations have been shown to increase the transport of P-gp substrates in vitro, in vivo studies in rats have shown that a higher surfactant concentration is needed to increase the oral absorption of e.g. the P-gp substrates digoxin and etoposide. The aim of the present study was to investigate if intestinal digestion of surfactants could be the reason for this deviation between in vitro and in vivo data. Therefore, Kolliphor EL, Brij-L23, Labrasol and polysorbate 20 were investigated for their ability to inhibit P-gp and increase digoxin absorption in vitro. Transport studies were performed in Caco-2 cells, while P-gp inhibition and cell viability assays were performed in MDCKII-MDR1 cells. Polysorbate 20, Kolliphor EL and Brij-L23 increased absorptive transport and decreased secretory digoxin transport in Caco-2 cells, whereas only polysorbate 20 and Brij-L23 showed P-gp inhibiting properties in the MDCKII-MDR1 cells. Polysorbate 20 and Brij-L23 were chosen for in vitro digestion prior to transport- or P-gp inhibiting assays. Brij-L23 was not digestible, whereas polysorbate 20 reached a degree of digestion around 40%. Neither of the two surfactants showed any significant difference in their ability to affect absorptive or secretory transport of digoxin after pre-digestion. Furthermore, the P-gp inhibiting effects of polysorbate 20 were not decreased significantly. In conclusion, the mechanism behind the non-ionic surfactant mediated in vitro P-gp inhibition seemed independent of the intestinal digestion and the results presented here did not suggest it to be the cause of the observed discrepancy between in vitro and in vivo.

Chinese bayberry (Myrica rubra Sieb. et Zucc.) leaves proanthocyanidins inhibit intestinal glucose transport in human Caco-2 cells.

Background: The hypoglycemic effects of Chinese bayberry leaves proanthocyanidins (BLPs) have been demonstrated. It is unclear, nevertheless, whether BLPs reduced postprandial blood glucose levels by regulating glucose uptake and glucose transport. Method: This study investigated the effect of BLPs (25, 50, and 100μg/mL) on glucose uptake and glucose transport in human intestinal epithelial cells (Caco-2 cells). The uptake of 2-Deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl) amino]-D-glucose (2-NBDG) and disaccharidases activity in Caco-2 cells were measured. The glucose transport ability across the cell membrane was determined using the established Caco-2 monolayer model. The transcript and protein levels of key glucose transporters were analyzed using real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting, respectively. Results: The results showed that BLPs significantly decreased glucose uptake and disaccharidases activity (p < 0.05). Otherwise, BLPs treatment obviously inhibited glucose transport across the Caco-2 monolayer in both simulated-fast (5mM glucose) and simulated-fed (25mM glucose) conditions. It was attributed to the suppression of glucose transporter2 (GLUT2) and sodium-dependent glucose cotransporter 1 (SGLT1) by BLPs. BLPs were found to significantly downregulated the transcript level and protein expression of glucose transporters (p < 0.05). Meanwhile, the mRNA expression of phospholipase C (PLC) and protein kinase C (PKC) involved in the signaling pathway associated with glucose transport were decreased by BLPs. Conclusion: These results suggested that BLPs inhibited intestinal glucose transport via inhibiting the expression of glucose transporters. It indicated that BLPs could be potentially used as a functional food in the diet to modulate postprandial hyperglycemia.

A Prunus avium L. Infusion Inhibits Sugar Uptake and Counteracts Oxidative Stress-Induced Stimulation of Glucose Uptake by Intestinal Epithelial (Caco-2) Cells.

Sweet cherry (Prunus avium L.) is among the most valued fruits due to its organoleptic properties and nutritional worth. Cherry stems are rich in bioactive compounds, known for their anti-inflammatory and antioxidant properties. Innumerable studies have indicated that some bioactive compounds can modulate sugar absorption in the small intestine. In this study, the phenolic profile of a cherry stem infusion was investigated, as well as its capacity to modulate intestinal glucose and fructose transport in Caco-2 cells. Long-term (24 h) exposure to cherry stem infusion (25%, v/v) significantly reduced glucose (3H-DG) and fructose (14C-FRU) apical uptake, reduced the apical-to-basolateral Papp to 3H-DG, and decreased mRNA expression levels of the sugar transporters SGLT1, GLUT2 and GLUT5. Oxidative stress (induced by tert-butyl hydroperoxide) caused an increase in 3H-DG uptake, which was abolished by the cherry stem infusion. These findings suggest that cherry stem infusion can reduce the intestinal absorption of both glucose and fructose by decreasing the gene expression of their membrane transporters. Moreover, this infusion also appears to be able to counteract the stimulatory effect of oxidative stress upon glucose intestinal uptake. Therefore, it can be a potentially useful compound for controlling hyperglycemia, especially in the presence of increased intestinal oxidative stress levels.

Moringa oleifera Leaves Protein Enhances Intestinal Permeability by Activating TLR4 Upstream Signaling and Disrupting Tight Junctions.

Changes in intestinal mucosal barrier permeability lead to antigen sensitization and mast cell-mediated allergic reactions, which are considered to play important roles in the occurrence and development of food allergies. It has been suggested that protein causes increased intestinal permeability via mast cell degranulation, and we investigated the effect of camellia Moringa oleifera leaves protein on intestinal permeability and explored its role in the development of food allergies. The current study investigated the effect of M. oleifera leaves protein on intestinal permeability through assessments of transepithelial electrical resistance (TEER) and transmembrane transport of FITC-dextran by Caco-2 cells. The expression levels of Toll-like receptor 4 (TLR4), IL-8, Occludin, Claudin-1, and perimembrane protein family (ZO-1) were detected by real-time PCR and Western blotting. The effect of M. oleifera leaves protein on intestinal permeability was verified in mice in vivo. The serum fluorescence intensity was measured using the FITC-dextran tracer method, and the expression of tight junction proteins was detected using Western blotting. The results showed that M. oleifera leaves protein widened the gaps between Caco-2 cells, reduced transmembrane resistance, and increased permeability. This protein also reduced the mRNA and protein levels of Occludin, Claudin-1, and ZO-1. Animal experiments showed that intestinal permeability was increased, and that the expression of the tight junction proteins Occludin and Claudin-1 were downregulated in mice. This study shows that M. oleifera leaves protein has components that increase intestinal permeability, decrease tight junction protein expression, promote transmembrane transport in Caco-2 cells, and increase intestinal permeability in experimental animals. The finding that M. oleifera leaves active protein increases intestinal permeability suggests that this protein may be valuable for the prevention, diagnosis, and treatment of M. oleifera leaves allergy.

D-allulose reduces postprandial glucose absorption in small intestine by competitive binding to glucose transport sites

d-allulose, a C3-epimer of d-fructose, is a naturally occurring non-metabolic sugar found in small amounts. Since d-allulose can inhibit the intestinal absorption of glucose,it is necessary to investigate the role of the sodium-coupled glucose cotransporter 1 (SGLT1) in intestinal transport of d-allulose. In this study, the transcellular pathway of d-allulose in small intestinal epithelial cells was investigated by constructing a monolayer model of Caco-2 cells and in situ single-pass intestinal perfusion experiment. We observed a notable decrease in the permeation rate of d-allulose with the addition of phlorizin, a SGLT1 inhibitor, and that phloretin, a GLUT2 inhibitor, leads to a moderate decrease in the permeation rate. This suggests that both SGLT1 and GLUT2 can mediate the transport of d-allulose in small intestine. These observations were supported by computer molecular simulation. Additionally, the mRNA abundance of sugar transporters in Caco-2 cells treated with d-allulose were decreased, determined by quantitative real-time PCR. This study suggests that d-allulose can competitively bind to the sugar transport sites and reduce the mRNA abundance of sugar transporter proteins within the small intestine to effect postprandial glucose absorption.

Hydrolysates of hemp (Cannabis sativa L.) seed meal: Characterization and their inhibitory effect on α-glucosidase activity and glucose transport in Caco-2 cells

Due to the lack of high value-added products and the rough utilization of hemp protein, which has the effect of regulating blood glucose, as well as the adverse effects of glucose-lowering drugs currently on the market, it is urgent to develop new safe and effective α-glucosidase inhibitors as substitutes for existing hypoglycemic drugs. Therefore, this study explored the physical and chemical properties, antioxidant activity, and inhibitory mechanism of α-glucosidase activity of non-dehulled hemp seed meal hydrolysate prepared by controlled enzymatic hydrolysis technology, as well as its inhibitory of α-glucosidase and glucose transmembrane transport in Caco-2 cells. Kinetic experiments indicated that the inhibition of α-glucosidase by hemp seed meal hydrolysate was reversible mixed inhibition. Cell experiments revealed that the hydrolysate inhibited both intracellular disaccharidase and the transport of glucose at different concentrations. In conclusion, the hemp seed meal hydrolysate can inhibit the activity of α-glucosidase and has potential value and application prospects in hypoglycemic effect.

Optimisation preparation, physicochemical properties, and glucose transport regulation by polysaccharides from Liubao brick tea

AbstractIn this study, a water-soluble novel polysaccharide called TPS was successfully prepared and isolated from Liubao tea. The optimal extraction conditions resulted in a yield of 10.70% for the crude TPS. The purified TPS exhibited unique physicochemical properties and structural characteristics. It was identified as an acidic polysaccharide with trace binding proteins, with a →4)-α-D-Galp-(1→) residue. The purified TPS had a dense and uneven appearance, potential crystallisation characteristics, and structural stability. Importantly, it demonstrated the ability to inhibit glucose transport in Caco-2 cells by down-regulating the expression of sodium/glucose cotransporter 1 (SGLT1) and glucose transporter 2 (GLUT2), leading to a hypoglycemic effect. These findings highlight the potential of TPS from Liubao tea as a functional food or additive with hypoglycaemic properties.

The Transport and Uptake of Resveratrol Mediated via Glucose Transporter 1 and Its Antioxidant Effect in Caco-2 Cells.

Resveratrol has anti-inflammatory, anti-cancer, and anti-aging pharmacological activities. There is currently a gap in academic research regarding the uptake, transport, and reduction of H2O2-induced oxidative damage of resveratrol in the Caco-2 cell model. This study investigated the role of resveratrol in the uptake, transport, and alleviation of H2O2-induced oxidative damage in Caco-2 cells. In the Caco-2 cell transport model, it was observed that the uptake and transport of resveratrol (10, 20, 40, and 80 μM) were time dependent and concentration dependent. Different temperatures (37 °C vs. 4 °C) could significantly affect the uptake and transportation of resveratrol. The apical to basolateral transport of resveratrol was markedly reduced by STF-31, a GLUT1 inhibitor, and siRNA intervention. Furthermore, resveratrol pretreatment (80 μM) improves the viability of Caco-2 cells induced by H2O2. In a cellular metabolite analysis combined with ultra-high performance liquid chromatography-tandem mass spectrometry, 21 metabolites were identified as differentials. These differential metabolites belong to the urea cycle, arginine and proline metabolism, glycine and serine metabolism, ammonia recycling, aspartate metabolism, glutathione metabolism, and other metabolic pathways. The transport, uptake, and metabolism of resveratrol suggest that oral resveratrol could prevent intestinal diseases caused by oxidative stress.

D-Optimal Design and Development of a Koumine-Loaded Microemulsion for Rheumatoid Arthritis Treatment: In vivo and in vitro Evaluation.

Koumine (KME) is the most abundant active ingredient separated from Gelsemium elegans Benth and exhibits a significant therapeutic effect on rheumatoid arthritis (RA). It is a lipophilic compound with poor aqueous solubility, and there is an urgent need to develop novel dosage forms of KME and promote its clinical application for the treatment of RA. The aim of this study was to design and develop KME-loaded microemulsions (KME-MEs) for the effective management of RA. The composition of the microemulsion was selected by carrying out a solubility study and generating pseudoternary phase diagrams, and further optimized by D-Optimal design. The optimized KME-MEs was evaluated for particle size, viscosity, drug release, storage stability, cytotoxicity, cellular uptake, Caco-2 cell transport and everted gut sac investigations. In vivo fluorescence imaging and the therapeutic effects of KME and KME-MEs on collagen-induced arthritis (CIA) rats were also evaluated. The optimized microemulsion contained 8% oil, 32% Smix (surfactant/cosurfactant) and 60% water and was used for in vivo and in vitro studies. The optimal KME-MEs exhibited a small globule size of 18.5 ± 0.14 nm and good stability over 3 months, and the release kinetics followed a first-order model. These KME-MEs had no toxic effect on Caco-2 cells but were efficiently internalized into the cytoplasm. Compared to KME, the KME-MEs displayed significantly increased permeability and absorption in Caco-2 cell monolayer assay and ex vivo everted gut sac experiment. As expected, the KME-MEs attenuated the progression of RA in CIA rats and were more effective than free KME with a reduced frequency of administration. The KME-MEs improved the solubility and therapeutic efficacy of KME by employing formulation technology. These results provide a promising vehicle for the oral delivery of KME to treat RA and have attractive potential for clinical translation.

Identification and evaluation of antioxidant activity of bioactive casein-derived peptides during in vitro digestion and transepithelial transport in Caco-2 cells

Dairy products are important sources of bioactive (antibacterial, antithrombotic, antihypertensive, immunomodulatory, and antioxidative) peptides, that need to be released from the target proteins. In the present study, bovine milk casein protein was hydrolyzed by pancreatin and trypsin (4 and 24 h) to evaluate the hydrolyses efficiency (ninhydrin reaction); to elucidate the sequence of casein-derived peptides (SDS-PAGE, LC-ESI-TOF-MS); and to assess the peptides antioxidant activity (DPPH and ORAC), bioactivity in silico, bioaccessibility after in vitro digestion, and bioavailablility by transepithelial transport in Caco-2 cells. The hydrolysis degree increased with the incubation time, with evident degradation of casein-derived proteins into low molecular weight peptides (<5 kDa) after 4 and 24 h incubation. Pancreatin showed higher hydrolysis degree (91%) than trypsin (21%). An increase in antioxidant activity was observed with increasing incubation time, with higher antioxidant effect observed for trypsin derived peptides (47% reduction of free radicals; 32112 μM Trolox equivalents) than pancreatin derived peptides (15% reduction; 2862 μM Trolox equivalents). A total of 69 caseins derived peptides were identified after trypsin (33 peptides) and pancreatin (36 peptides) hydrolysis for 24 h; with 26 peptides released from β-casein, 21 from α-s1-casein, 15 from α-s2-casein, and 7 from k-casein hydrolysis. Some of these peptides were described as antioxidant, anti-inflammatory, and antihypertensive. After in vitro digestion 123 peptides were found in gastric (56 peptides), duodenal (43 peptides) and colonic (24 peptides) fraction; while five peptides were bioavailable by crossing the intestinal barrier, with increased peptides’ abundance after trypsin hydrolysis treatment.

Effect and Mechanism of Theaflavins on Fluoride Transport and Absorption in Caco-2 Cells.

This paper investigated the effect and mechanism of theaflavins (TFs) on fluoride (F-) uptake and transport in the Caco-2 cell model through structural chemistry and transcriptome analysis. The results showed that the four major TFs (TF, TF3G, TF3'G and TFDG) at a 150 μg/mL concentration could all significantly decrease F- transport in Caco-2 cells after 2 h of treatment and, at 2 μg/mL F- concentration, the F- transport was more inclined to efflux. During transport, the F- retention in Caco-2 cells was significantly increased by TF3G while it was clearly decreased by TF. The interaction between TFs and F- was analyzed by Raman spectroscopy and isothermal titration calorimetry, and F- was shown to affect the π bond vibration on the benzene ring of TFs, thus influencing their stability. Additionally, F- showed weak binding to TF3G, TF3'G and TFDG, which may inhibit F- transport and absorption in the Caco-2 cell line. Transcriptome and RT-PCR analysis identified three key differentially expressed genes related to cell permeability, and TFs can be assumed to mediate F- transport by regulating the expression of permeability-related genes to change cell monolayer permeability and enhance cell barrier function; however, this needs to be further elucidated in future studies.

Folic acid-modified reverse micelle-lipid nanocapsules overcome intestinal barriers and improve the oral delivery of peptides

The oral absorption of exenatide, a type 2 diabetes medication, can be increased by employing lipid nanocapsules (LNC). To increase mucus permeability and exenatide intestinal absorption, reverse micelle lipid nanocapsules (RM-LNC) were prepared and their surface was modified with DSPE-PEG-FA. The RM-LNC with surface modification of DSPE-PEG-FA (FA-RM-LNC) were able to target enterocytes and reduce mucus aggregation in the intestine. Furthermore, in vitro absorption at different intestinal sites and flip-flop intestinal loop experiments revealed that LNCs with surface modification significantly increased their absorption efficiency in the small intestine. FA-RM-LNC delivers more drugs into Caco-2 cells via caveolin-, macrophagocytosis-, and lipid raft-mediated endocytosis. Additionally, the enhanced transport capacity of FA-RM-LNC was observed in a study of monolayer transport in Caco-2 cells. The oral administration of exenatide FA-RM-LNC resulted in a prolonged duration of hypoglycemia in diabetic mice and a relative bioavailability (BR) of up to 7.5% in rats. In conclusion, FA-RM-LNC can target enterocytes and has promising potential as a nanocarrier for the oral delivery of peptides.

Inhibition of Transglutaminase 2 as a Therapeutic Strategy in Celiac Disease-In Vitro Studies in Intestinal Cells and Duodenal Biopsies.

Enzymatic modification of gliadin peptides by human transglutaminase 2 (TG2) is a key mechanism in the pathogenesis of celiac disease (CD) and represents a potential therapeutic target. Recently, we have identified the small oxidative molecule PX-12 as an effective inhibitor of TG2 in vitro. In this study, we further investigated the effect of PX-12 and the established active-site directed inhibitor ERW1041 on TG2 activity and epithelial transport of gliadin peptides. We analyzed TG2 activity using immobilized TG2, Caco-2 cell lysates, confluent Caco-2 cell monolayers and duodenal biopsies from CD patients. TG2-mediated cross-linking of pepsin-/trypsin-digested gliadin (PTG) and 5BP (5-biotinamidopentylamine) was quantified by colorimetry, fluorometry and confocal microscopy. Cell viability was tested with a resazurin-based fluorometric assay. Epithelial transport of promofluor-conjugated gliadin peptides P31-43 and P56-88 was analyzed by fluorometry and confocal microscopy. PX-12 reduced TG2-mediated cross-linking of PTG and was significantly more effective than ERW1041 (10 µM, 15 ± 3 vs. 48 ± 8%, p < 0.001). In addition, PX-12 inhibited TG2 in cell lysates obtained from Caco-2 cells more than ERW1041 (10 µM; 12 ± 7% vs. 45 ± 19%, p < 0.05). Both substances inhibited TG2 comparably in the intestinal lamina propria of duodenal biopsies (100 µM, 25 ± 13% vs. 22 ± 11%). However, PX-12 did not inhibit TG2 in confluent Caco-2 cells, whereas ERW1041 showed a dose-dependent effect. Similarly, epithelial transport of P56-88 was inhibited by ERW1041, but not by PX-12. Cell viability was not negatively affected by either substance at concentrations up to 100 µM. PX-12 did not reduce TG2 activity or gliadin peptide transport in confluent Caco-2 cells. This could be caused by rapid inactivation or degradation of the substance in the Caco-2 cell culture. Still, our in vitro data underline the potential of the oxidative inhibition of TG2. The fact that the TG2-specific inhibitor ERW1041 reduced the epithelial uptake of P56-88 in Caco-2 cells further strengthens the therapeutic potential of TG2 inhibitors in CD.

Diethylene glycol monoethyl ether-mediated nanostructured lipid carriers enhance trans-ferulic acid delivery by Caco-2 cells superior to solid lipid nanoparticles.

This work aimed to compare the performance of trans-ferulic acid-encapsulated nanostructured lipid carriers (NLCs) and solid lipid nanoparticles (SLNs) for transport by Caco-2 cells. The NLC particles (diameter: 102.6 nm) composed of Compritol® 888 ATO, ethyl oleate, Cremophor® EL, and Transcutol® P were larger than the SLNs (diameter: 86.0 nm) formed without liquid lipid (ethyl oleate), and the former had a higher encapsulation efficiency for trans-ferulic acid (p < 0.05). In vitro cultured Caco-2 cell transport was used to simulate intestinal absorption, and the cellular uptake of NLCs was higher than that of SLNs (p < 0.05). Compared to SLNs, NLCs greatly enhanced trans-ferulic acid permeation through the MillicellTM membrane (p < 0.05). This work confirms that NLCs have better properties than SLNs in terms of increasing drug transport by Caco-2 cells. This helps to comprehend the approach by which NLC-mediated oral bioavailability of trans-ferulic acid is better than that mediated by SLNs, as shown in our previous report.

Cinnamon free phenolic extract regulates glucose absorption in intestinal cells by inhibiting glucose transporters

Cinnamon is a traditional herbal medicine that is a valuable source of bioactive phenolic compounds. In this study, we determined the effects of cinnamon free phenolic extract (CFPE) on glucose transport in Caco-2 cells and its possible mechanisms of action. First, the contents of phenolic compounds and flavonoids in bark were compared among four cinnamon cultivars. The ‘Taiwan’ cultivar had the highest contents of these compounds, and the CFPE was prepared from it. A Caco-2 monolayer was established, and the effect of CFPE on glucose transport across the monolayer was determined. The results showed that CFPE (at 150–300 μg/mL) suppressed glucose transport across the monolayer in a dose-dependent manner. Procyanidin C1, procyanidin B2, procyanidin B1, procyanidin B3, procyanidin A2, and (−)-epicatechin derivatives in CFPE may have contributed to its suppressive effect. Treatment with CFPE decreased the transcript levels of SGK1 encoding serum and glucocorticoid-inducible kinase and PLC/PKC encoding phospholipase C/protein kinase C, which are involved in the signaling pathway associated with glucose transport; and the transcript levels of SGLT1 encoding sodium/glucose cotransporter 1 and GLUT2 encoding glucose transporter 2, the key glucose transporters in this pathway. These findings suggest that CFPE inhibits glucose transport via its effects on the signaling pathway and glucose transporters involved in glucose absorption in intestinal cells. Thus, CFPE has potential applications in preventing postprandial hyperglycemia.

Dynamic gastrointestinal digestion/intestinal permeability of encapsulated and nonencapsulated Brazilian red propolis: Active compounds stability and bioactivity

The objectives were to investigate the effect of dynamic gastrointestinal digestion/Caco-2 cell transport on active compounds stability and antioxidant/anti-inflammatory activities of the ethanolic extract of Brazilian red propolis (EEBRP), whether encapsulated or not; and the in vivo acute toxicity of the EEBRP after digestion. Eight isoflavonoids, one flavanone, and one chalcone were identified by HPLC-ESI-QTOF-MS, and quantified by HPLC-PDA. Bioaccessibility was higher for the encapsulated EEBRP (21.4%-57.6%) than for the nonencapsulated (19.3%-30.2%). Conversely, the Caco-2 cell transport was higher for the nonencapsulated EEBRP. Similarly, the nonencapsulated EEBRP showed higher ability to scavenge reactive oxygen species, which was especially attributed to calycosin, and to decrease NF-κB activation, and the levels of TNF-α and CXCL2/MIP-2 after Caco-2 cell transport. Hence, there is an indication that EEBRP is a promising alternative dietary source of bioavailable isoflavonoids. Further studies on encapsulation should be encouraged to improve bioactivity, and expand its food applications.