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The fruits of Rosa laxa Retz. (FRL) have a long history of medicinal use, known for their rich composition of flavonoids, polyphenols, amino acids, sugars, and other bioactive compounds. FRL exhibits pharmacological effects such as antioxidant, antiviral, antibacterial, and antitumor activities, making it a valuable resource with significant development potential in both the food and pharmaceutical industries. This study employed a response surface methodology combined with ultra-high-performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-TQ-MS) to optimize FRL extraction. Reflux extraction was determined to be the most effective method with the following optimized parameters: 65% ethanol extraction solvent, material-to-liquid ratio of 1:35 (g/mL), and extraction time of 140 min, resulting in the FRL extract (FRLE). Under these optimized conditions, the extracted amount was extract was 51.00 ± 1.07%, the average content of total polyphenols was 126.55 ± 2.61 mg/g, and the average content of euscaphic acid was 2.90 ± 0.08 mg/g, demonstrating the efficiency of the extraction method. Using the Caco-2 cell model, the study investigated the absorption characteristics of euscaphic acid and tiliroside within FRLE. Results indicated that with increasing time, the absorbed amount (Qr) of euscaphic acid and tiliroside gradually increased, with an efflux ratio (RB→A/A→B) of less than 1.5, suggesting bidirectional drug transport with no significant directionality. Upon the addition of P-glycoprotein (P-gp) inhibitors Verapamil (Ver) and Ciclosporin A (CsA), as well as the chelating agent ethylenebis (oxyethylenenitrilo) tetraacetic acid (EGTA), Qr and Papp values notably increased, indicating that these two components are P-gp substrates with cellular basolateral efflux transport. Additionally, optimal absorption efficiency was observed under weakly acidic conditions (pH 6.0). In conclusion, euscaphic acid and tiliroside in FRLE demonstrated good membrane permeability, primarily relying on passive diffusion for absorption. This study offers experimental insights into the intestinal absorption of FRL in vivo. [ABSTRACT FROM AUTHOR]

The fruits of Rosa laxa Retz. (FRL) have a long history of medicinal use, known for their rich composition of flavonoids, polyphenols, amino acids, sugars, and other bioactive compounds. FRL exhibits pharmacological effects such as antioxidant, antiviral, antibacterial, and antitumor activities, making it a valuable resource with significant development potential in both the food and pharmaceutical industries. This study employed a response surface methodology combined with ultra-high-performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-TQ-MS) to optimize FRL extraction. Reflux extraction was determined to be the most effective method with the following optimized parameters: 65% ethanol extraction solvent, material-to-liquid ratio of 1:35 (g/mL), and extraction time of 140 min, resulting in the FRL extract (FRLE). Under these optimized conditions, the extracted amount was extract was 51.00 ± 1.07%, the average content of total polyphenols was 126.55 ± 2.61 mg/g, and the average content of euscaphic acid was 2.90 ± 0.08 mg/g, demonstrating the efficiency of the extraction method. Using the Caco-2 cell model, the study investigated the absorption characteristics of euscaphic acid and tiliroside within FRLE. Results indicated that with increasing time, the absorbed amount (Qr) of euscaphic acid and tiliroside gradually increased, with an efflux ratio (RB→A/A→B) of less than 1.5, suggesting bidirectional drug transport with no significant directionality. Upon the addition of P-glycoprotein (P-gp) inhibitors Verapamil (Ver) and Ciclosporin A (CsA), as well as the chelating agent ethylenebis (oxyethylenenitrilo) tetraacetic acid (EGTA), Qr and Papp values notably increased, indicating that these two components are P-gp substrates with cellular basolateral efflux transport. Additionally, optimal absorption efficiency was observed under weakly acidic conditions (pH 6.0). In conclusion, euscaphic acid and tiliroside in FRLE demonstrated good membrane permeability, primarily relying on passive diffusion for absorption. This study offers experimental insights into the intestinal absorption of FRL in vivo.

In order to investigate the mechanism of aspartic acid, glutamic acid and their glycine dipeptides on calcium ion uptake, the isothermal titration calorimetry technique, electrochemistry, and Caco-2 cell model combined with quantum mechanical calculation (density functional theory) were used to investigate the interactions between aspartic acid and glutamic acid, as well as their glycine dipeptides. The results showed that aspartic acid and glutamic acid form complexes with calcium ions through exothermic reactions driven by enthalpy and entropy, while their dipeptides interacted with calcium ions by entropy-driven endothermic reactions. In addition, dipeptides exhibited stronger calcium binding capacity than the single amino acids. Quantum chemical calculations showed that the carboxyl groups in the amino acid/dipeptide were the main binding site of calcium ions, while under alkaline conditions, the amino group could also participate in calcium binding, leading to a calcium binding site shift. Caco-2 cell uptake experiments showed that aspartic acid, glutamic acid and their dipeptides could promote calcium absorption. Among them, Gly-Glu dipeptide had the best promotion effect, and the calcium absorption rate was 1.33±0.115. Furthermore, there was no clear correlation between the ability to promote calcium absorption and the ability to bind calcium ions. However, it was more closely related to its electron affinity. The results elucidated the interactions between aspartic acid, glutamic acid and their glycine dipeptides and calcium ions, providing scientific basis for further development of calcium supplements

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Iron deficiency anemia (IDA) is a common nutritional problem, but traditional iron supplements cause many adverse reactions. Thus, the development of a novel iron supplement might be significant for the treatment of IDA. This study aimed to study the transport mechanism of Flammulina velutipes polysaccharide-iron complex (FVP1-Fe(III)) in Caco-2 cells and the therapeutic effect on IDA rats, as well as the influence on gut microbiota in vivo. These results showed that in vitro, the uptake of FVP1-Fe(III) was mediated by sodium-dependent glucose transporter-1 (SGLT1) and facilitated glucose transporter-2 (GLUT2) and GLUT2 played a dominant function. The multidrug resistance-associated protein-2 (MRP-2) was involved in the efflux of FVP1-Fe(III) across the Caco-2 cells. In vivo, FVP1-Fe(III) had a better restorative effect on blood parameters and iron status indicators in rats with IDA as compared with FeSO4 and exerted this effect by downregulating the expression of hepcidin. FVP1-Fe(III) could also regulate gut microbiota dysbiosis in iron deficiency rats by returning the relative abundance of gut microbiota to the normal level. Besides, as a dietary factor, vitamin C (vit C) could enhance the therapeutic effect of FVP1-Fe(III). These present findings showed that FVP1-Fe(III) could be exploited as a novel iron supplement to treat IDA.

Tandospirone citrate (TDS) is commonly used for the treatment of patients with generalized anxiety disorder in clinical practice, and several studies are developing new indications for TDS. However, the in vivo processes and absorption properties of TDS have not been systematically investigated. In this work, we conducted a comprehensive investigation using in vivo, in vitro, and ex vivo approaches, involving animal and cellular models, to examine the pharmacokinetic properties and absorption mechanisms of TDS. The results of in vivo studies revealed that the half-life (t1/2) of TDS was 1.380 ± 0.46 h and 1.224 ± 0.39 h following intragastric (i.g.) and intravenous (i.v.) administration of 20 mg/kg TDS, respectively. This indicates that TDS is rapidly eliminated in rats. The area under the curve (AUC) of TDS after i.g. and i.v. administration was 114.7 ± 40 ng/mL*h and 48,400 ± 19,110 ng/mL*h, respectively, and the absolute bioavailability of TDSwas found to be low (0.24%). Furthermore, TDS was extensively metabolized in rats, with the AUCof themajor active metabolite [1-[2-pyrimidyl]-piperazine] being approximately 16.38-fold higher than that of TDS after i.g. administration. The results from the in vitro Caco-2 cell model and ex vivo everted gut sac experiment demonstrated that TDS exhibited good permeability, and its transport was influenced by concentration, temperature, and pH. Passive diffusion was identified as the main absorption mechanism. In conclusion, TDS is classified as a Biopharmaceutics Classification System (BCS) class I drug, characterized by high solubility and permeability. The low absolute bioavailability of TDS may be attributed to its rapid metabolism. The pharmacokinetic data and absorption characteristics obtained in this study provide fundamental information for the further development and utilization of TDS. [ABSTRACT FROM AUTHOR]

Antarctic krill (Euphausia superba) is the world's largest resource of animal proteins and is thought to be a high-quality resource for future marine healthy foods and functional products. Therefore, Antarctic krill was degreased and separately hydrolyzed using flavourzyme, pepsin, papain, and alcalase. Protein hydrolysate (AKH) of Antarctic krill prepared by trypsin showed the highest Ca-chelating rate under the optimized chelating conditions: a pH of 8.0, reaction time of 50 min, temperature of 50 °C, and material/calcium ratio of 1:15. Subsequently, fourteen Ca-chelating peptides were isolated from APK by ultrafiltration and a series of chromatographic methods and identified as AK, EAR, AEA, VERG, VAS, GPK, SP, GPKG, APRGH, GVPG, LEPGP, LEKGA, FPPGR, and GEPG with molecular weights of 217.27, 374.40, 289.29, 459.50, 275.30, 300.36, 202.21, 357.41, 536.59, 328.37, 511.58, 516.60, 572.66, and 358.35 Da, respectively. Among fourteen Ca-chelating peptides, VERG presented the highest Ca-chelating ability. Ultraviolet spectrum (UV), Fourier Transform Infrared (FTIR), and scanning electron microscope (SEM) analysis indicated that the VERG-Ca chelate had a dense granular structure because the N-H, C=O and -COOH groups of VERG combined with Ca2+. Moreover, the VERG-Ca chelate is stable in gastrointestinal digestion and can significantly improve Ca transport in Caco-2 cell monolayer experiments, but phytate could significantly reduce the absorption of Ca derived from the VERG-Ca chelate. Therefore, Ca-chelating peptides from protein hydrolysate of Antarctic krill possess the potential to serve as a Ca supplement in developing healthy foods. [ABSTRACT FROM AUTHOR]

Dietary polyphenols with great antidiabetic effects are the most abundant components in edible products. Dietary polyphenols have attracted attention as dipeptidyl peptidase-IV (DPP-IV) inhibitors and indirectly improve insulin secretion. The DPP-IV inhibitory activities of dietary polyphenols depend on their structural diversity. Screening methods that can be used to rapidly and accurately identify potential polyphenol DPP-IV inhibitors are urgently needed. This review focuses on the relationship between the structures of dietary polyphenols and their DPP-IV inhibitory effects. Different characterization methods used for polyphenols as DPP-IV inhibitors have been summarized and compared. We conclude that the position and number of hydroxyl groups, methoxy groups, glycosylated groups, and the extent of conjugation influence the efficiency of inhibition of DPP-IV. various combinations of methods, such as in-vitro enzymatic inhibition, ex-vivo/in-vivo enzymatic inhibition, cell-based in situ, and in-silico virtual screening, are used to evaluate the DPP-IV inhibitory effects of dietary polyphenols. Further investigations of polyphenol DPP-iv inhibitors will improve the bioaccessibility and bioavailability of these bioactive compounds. exploration of (i) dietary polyphenols derived from multiple targets, that can prevent diabetes, and (ii) actual binding interactions via multispectral analysis, to understand the binding interactions in the complexes, is required. [ABSTRACT FROM AUTHOR]

Iron deficiency anemia (IDA) is a global health concern affecting one‐third of the world's population, particularly those dominated by plant‐based food. Fortifying staple foods with iron has been an effective strategy for preventing IDA. Pneumatophorus japonicus is an essential economic fish in China. Pneumatophorus japonicus dark meat is usually underutilized as a byproduct, though it contains bounteous nutrients, including heme iron (10.50 mg/100 g). This study aimed to investigate the iron bioavailability of P. japonicus dark meat and to evaluate its potential as an iron fortifier for whole‐wheat flour, a typical staple food, using an in vitro digestion/Caco‐2 cell culture system. Our results suggested the excellent iron bioavailability of P. japonicus dark meat in comparison with beef (a heme dietary iron reference), whole‐wheat flour (a non‐heme dietary iron reference), and FeSO4 (a conventional iron supplement). The addition of P. japonicus dark meat notably enhanced iron solubility, bioavailability, and protein digestibility of whole‐wheat flour. The flour‐dark meat mixture yielded 1.96 times the iron bioavailability compared to beef per gram. The iron bioavailability was further improved by adding vitamin C, a commonly used dietary factor, at the Vc/iron mass ratio of 2:100‐5:100. Our findings reveal the promise of P. japonicus dark meat as a significant source of bioavailable iron, providing a basis for developing fish byproducts as alternatives for iron supplementation. Practical Application: This study investigated the iron bioavailability of Pneumatophorus japonicus meat using in vitro digestion/Caco‐2 cell culture system. These results could be used to improve the utilization of Pneumatophorus japonicus byproduct (dark meat) and develop the potential of the byproduct as an iron fortifier for whole‐wheat flour. [ABSTRACT FROM AUTHOR]

Antarctic krill (Euphausia superba) is the world’s largest resource of animal proteins and is thought to be a high-quality resource for future marine healthy foods and functional products. Therefore, Antarctic krill was degreased and separately hydrolyzed using flavourzyme, pepsin, papain, and alcalase. Protein hydrolysate (AKH) of Antarctic krill prepared by trypsin showed the highest Ca-chelating rate under the optimized chelating conditions: a pH of 8.0, reaction time of 50 min, temperature of 50 °C, and material/calcium ratio of 1:15. Subsequently, fourteen Ca-chelating peptides were isolated from APK by ultrafiltration and a series of chromatographic methods and identified as AK, EAR, AEA, VERG, VAS, GPK, SP, GPKG, APRGH, GVPG, LEPGP, LEKGA, FPPGR, and GEPG with molecular weights of 217.27, 374.40, 289.29, 459.50, 275.30, 300.36, 202.21, 357.41, 536.59, 328.37, 511.58, 516.60, 572.66, and 358.35 Da, respectively. Among fourteen Ca-chelating peptides, VERG presented the highest Ca-chelating ability. Ultraviolet spectrum (UV), Fourier Transform Infrared (FTIR), and scanning electron microscope (SEM) analysis indicated that the VERG-Ca chelate had a dense granular structure because the N-H, C=O and -COOH groups of VERG combined with Ca2+. Moreover, the VERG-Ca chelate is stable in gastrointestinal digestion and can significantly improve Ca transport in Caco-2 cell monolayer experiments, but phytate could significantly reduce the absorption of Ca derived from the VERG-Ca chelate. Therefore, Ca-chelating peptides from protein hydrolysate of Antarctic krill possess the potential to serve as a Ca supplement in developing healthy foods.

Pectin from the citrus peel waste has novel applications in food and biomedical industries. The present work focused on addressing iron deficiency, which is a global health concern, by developing a functional ingredient using pectin extracted from Assam lemon (Citrus limon Burm. F) and supplementing iron via the pectin‑iron complex (PIC). Extracted pectin was incubated with iron chloride hexahydrate (0.90–1.80 mM) for 180 h to optimize the complexation conditions, with the optimal concentration being 1.36 mM. The iron bioavailability and its absorption in the PIC was assessed using in-vitro simulation digestion and Caco-2 cell monolayers. The bioaccessible form of iron in the developed PIC during the intestinal phase was 5.34 ± 0.16%, which was negligible in pectin. The absorption of bioaccessible iron in the PIC was found to be 2.93 ± 0.03%. The results demonstrated that PIC could reduce iron deficiency and increase fibre intake, leading to several health benefits. [Display omitted] • Pectin-iron complex was in-vitro digested and introduced to Caco-2 monolayers. • PIC and pectin exhibited DE > 50% extending their application in the food system. • PIC exhibited stability under a simulated in vitro digestion system. [ABSTRACT FROM AUTHOR]

Arbutin is a naturally occurring glucoside extracted from plants, known for its antioxidant and tyrosinase inhibiting properties. It is widely used in cosmetic and pharmaceutical industries. With in-depth study of arbutin, its application in disease treatment is expanding, presenting promising development prospects. However, reports on the metabolic stability, plasma protein binding rate, and pharmacokinetic properties of arbutin are scarce. The aim of this study is to enrich the data of metabolic stability and pharmacokinetics of arbutin through the early pre-clinical evaluation, thereby providing some experimental basis for advancing arbutin into clinical research. We developed an efficient and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for determining arbutin in plasma. We investigated the metabolic and pharmacokinetic properties of arbutin through in vitro metabolism assay, cytochrome enzymes P450 (CYP450) inhibition studies, plasma protein binding rate analysis, Caco-2 cell permeability tests, and rat pharmacokinetics to understand its in vivo performance. In vitro studies show that arbutin is stable, albeit with some species differences. It exhibits low plasma protein binding (35.35 ± 11.03% ∼ 40.25 ± 2.47%), low lipophilicity, low permeability, short half-life (0.42 ± 0.30 h) and high oral bioavailability (65 ± 11.6%). Arbutin is primarily found in the liver and kidneys and is eliminated in the urine. It does not significantly inhibit CYP450 up to 10 μM, suggesting a low potential for drug interactions. Futhermore, preliminary toxicological experiments indicate arbutin's safety, supporting its potential as a therapeutic agent. This study provides a comprehensive analysis the drug metabolism and pharmacokinetics (DMPK) of arbutin, enriching our understanding of its metabolism stability and pharmacokinetics properties, It establishes a foundation for further structural optimization, pharmacological studies, and the clinical development of arbutin. [Display omitted] • A rapid and efficient LC-MS/MS assay for the determination of Arbutin has been developed. • Enrichment of drug metabolism and pharmacokinetics data for Arbutin. • The pharmacokinetic properties of arbutin and the factors that influence them were investigated. • Preparation of arbutin for entry into clinical development. [ABSTRACT FROM AUTHOR]

[Display omitted] • Germination significantly altered the phenolic metabolites of quinoa. • The bioaccessibilities of phenolic metabolites were improved by germination. • The transport rates of phenolic metabolites of quinoa were improved by germination. • Germinated quinoa modulated the gut microbiota composition and increased SCFAs. • Germinated quinoa had considerable α-amylase and α-glucosidase inhibitory activity. 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 Spirochaeo ta 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. [ABSTRACT FROM AUTHOR]

Degradable biopolymers with functional groups play a crucial role in the biomedical field. In this case, the influences of temperature and pH values on the degradation performance of poly (γ‐glutamic acid) (γ‐PGA) were fully explored by gel permeation chromatography. Further, γ‐PGA‐Ca was prepared by using calcium chloride to react with the low molecular weight γ‐PGA and characterized by Fourier transform infrared, differential scanning calorimetry test, gel permeation chromatography, atomic absorption spectrophotometric, Ca2+ release in vivo, and cytotoxicity experiments. Furthermore, Caco‐2 cell model was constructed to study the mechanism of γ‐PGA‐Ca intestinal absorption. Results indicated that low pH value and high temperature are the suitable conditions for the degradation of γ‐PGA. It also suggested that γ‐PGA‐Ca can be used as calcium supplements due to its high rate of absorption. [ABSTRACT FROM AUTHOR]

Iron deficiency remains a public health problem around the world due to low iron intake and/or bioavailability. FeSO4, ferrous succinate, and ferrous glycinate chelate are rich in iron but have poor bioavailability. To solve the problem of iron deficiency, following previous research studies, a thiolated human-like collagen-ironcomplex supplement with a high iron content was prepared in an anaerobic workstation. In addition, cell viability tests were evaluated after conducting an MTT assay, and a quantitative analysis of the thiolated human-like collagen-iron digesta samples was performed using the SDS-PAGE method coupled with gel filtration chromatography. The iron bioavailability was assessed using Caco-2 cell monolayers and iron-deficiency anemia mice models. The results showed that (1) one mole of thiolated human-like collagen-iron possessed approximately 35.34 moles of iron; (2) thiolated human-like collagen-iron did not exhibit cytotoxity and (3) thiolated human-like collagen- iron digesta samples had higher bioavailability than other iron supplements, including FeSO4, ferrous succinate, ferrous glycine chelate and thiolated human-like collagen-Fe iron. Finally, the iron bioavailability was significantly enhanced by vitamin C. These results indicated that thiolated human-like collagen-iron is a promising iron supplement for use in the future. [ABSTRACT FROM AUTHOR]

Background Induction or inhibition of drug transporting proteins by concomitantly administered drugs can cause serious drug-drug interactions (DDIs). However, in vitro assays currently available are mostly for studying the inhibitory potential of drugs on intestinal transporter proteins, rather than induction. Therefore, this study investigated the suitability of the frequently used intestinal Caco-2 cell line to predict transporter-mediated DDIs as caused by induction via activation of nuclear receptors. Methods TaqMan® low density arrays and LC-MS/MS based targeted proteomics were used to evaluate transporter expression in Caco-2 cells in comparison with jejunal tissue, in culture-time dependence studies and after incubation with different known inducers of drug metabolism and transport. Additionally, studies on ABCB1 function were performed using Transwell® assays with [3H]-digoxin and [3H]-talinolol as substrates after incubation with the prototypical inducers rifampicin, St John's wort, carbamazepine and efavirenz. Results The gene and protein expression pattern of drug transporters in Caco-2 cells and jejunal tissue differed considerably. For some transporters culture-time dependent differences in mRNA expression and/or protein abundance could be determined. Finally, none of the studied prototypical inducers showed an effect either on mRNA expression and protein abundance or on the function of ABCB1. Conclusion Differences in transporter expression in Caco-2 cells compared with jejunal tissue, as well as expression dependence on culture time must be considered in in vitro studies to avoid under- or overestimation of certain transporters. The Caco-2 cell model is not suitable for the evaluation of DDIs caused by transporter induction. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Recently, lactoferrin (Lf), a glycoprotein belonging to transferrin family, has received more attention for the discovery of its wide spectrum of functionalities. Among its important functionalities is its ability to bind Fe and its high stability against in vitro digestion. Galactooligosaccharides (GOS) also has functionality related to Fe bioaccessibility and it also positively affect Lf stability. This study aimed to evaluate the functionality of recombinant human Lf (rhLf) and GOS as factors that improve iron bioaccessibility in human milk. In this study, rhLf and GOS were added to First Infant Formula (FIF) in three concentrations (0.10, 0.15 and 0.20 and 3.3, 5 and 10 g 100 mL − 1 of the reconstituted formula, respectively), whether alone or in combination. In vitro digestion model was applied to different infant formulas to evaluate Fe solubility and the obtained digests were added to Caco-2 cell line to determine Fe bioaccessibility through the measurement of synthesized ferritin. The obtained results revealed that supplementation of formulas with rhLf and GOS enhanced Fe solubility to 66–97% which turns in an improvement of Fe bioaccessibility. Caco-2 cell ferritin content ranged from 6 to 46 ng per mg cell protein with 5–7.5 fold increases in cells incubated with digested samples containing both rhLF and GOS. Although mineral solubility is the most important factor, which affects on Fe bioaccessibility, other factors may also interfere with it, such as the expression of divalent metal transporter 1 (DMT1). The findings also revealed that rhLf is a highly stable protein, especially in the presence of GOS and more researches are needed to clarify this hidden effect of GOS. Thus, rhLf and GOS together are prominent components of human milk could improve Fe bioaccessibility and it is noteworthy that these finding must be taken into account during infant formula evolution to prevent some disease related to Fe deficiency. [ABSTRACT FROM AUTHOR]

Background: Salvianolic acid B (SalB) represents the most abundant and bio-active phenolic constituent among the water-soluble compounds of Salvia miltiorrhiza. But the therapeutic potential of SalB has been significantly restricted by its poor absorption. Methods: In this study, chitosans (CS) and CS nanoparticles (NPs) with different molecular weights (MWs), which have influence on the absorption of SalB, was also investigated. Results: As a preliminary study, water-soluble CS with various MWs (3, 30, 50, and 100 kDa) was chosen. We investigated the MW-dependent Caco-2 cell layer transport phenomena in vitro of CS and NPs at concentrations (4 μg/ml, w/v). SalB, in presence CS or NPs has no significant toxic effect on Caco-2 cell. As the MW increases, the absorption enhancing effect of CS increases. However, as the MW decreases, the absorption enhancing effect of NPs increases. The AUC0-∞ of the SalB-100 kDa CS was 4.25 times greater than that of free SalB. And the AUC0-∞ of the SalB-3 kDa NPs was 16.03 times greater than that of free SalB. Conclusion: CS and NPs with different MWs as the absorption enhancers can promote the absorption of SalB. And the effect on NPs is better than CS. [ABSTRACT FROM AUTHOR]

Iron (Fe) deficiency remains a public health problem. Deficiency is often due to low iron intake and/or iron bioavailability. Seaweeds are known to be rich in iron, but its bioavailability is poorly understood. Our objective was to evaluate common, edible seaweeds from Asia, Hawaii, and Maine as sources of iron by comparing iron content and bioavailability to spinach. Ten of 13 seaweeds analyzed contained more iron than spinach. Iron content ranged from 73 to 3490 μg/g dry matter (DM). Twenty percent of the Daily Value for iron could be obtained from just 4.3 g of dry sea lettuce, 5.1 g of dry rockweed, 9 g of dry wakame, or 13 g of dry nori. However, in vitro bioavailability studies indicated that, due to low absorption efficiencies, not all seaweeds would provide greater amounts of bioavailable Fe than spinach. Notable exceptions were nori and sea lettuce which provided 3 and 5-fold more bioavailable Fe, respectively. In addition, bioavailability was significantly enhanced by vitamin C in these two seaweeds. We conclude that certain seaweeds could be good sources of bioavailable iron. However, many seaweeds contained high levels of arsenic or other minerals which could limit regular consumption as a safe source of iron. [ABSTRACT FROM AUTHOR]

Alcalase-treated casein hydrolysates were separated into three hydrophobic chromatography fractions (HC-F1, HC-F2 and HC-F3) using YMC ODS C18 column. Simulated gastrointestinal (GI) digestion (stage I digestion) and Caco-2 cell absorption (stage II digestion) were sequentially applied for producing corresponding digests and adsorbates of collected peptide fractions. ANS probe and reverse-phase (RP)-HPLC were applied to detect peptide hydrophobicity, whereas trolox equivalent antioxidant capacity and oxygen radical antioxidant capacity were used to determine their antioxidant activity. Peptide nitrogen was used to evaluate bioavailability (BA) and remaining peptide content. In addition, RP-HPLC and electrospray ionization mass spectrometry were performed to obtain peptide sequences. Results showed that high hydrophobic peptide fractions (HC-F3) had excellent BA and remaining antioxidant activity, but poor digestive stability in stage I digestion. Two peptides, NTVP and IV, were identified from the adsorbate of HC-F3 to be GI-resistant peptides. Therefore, utilizing high hydrophobic peptides from casein as potential functional foods or nutraceuticals was feasible. [ABSTRACT FROM AUTHOR]

Iron intakes calculated from one-day weighed records were compared with those from same day analyzed duplicate diet composites collected from 120 Malawian women living in two rural districts with contrasting soil mineralogy and where threshing may contaminate cereals with soil iron. Soils and diet composites from the two districts were then subjected to a simulated gastrointestinal digestion and iron availability in the digests measured using a Caco-2 cell model. Median analyzed iron intakes (mg/d) were higher ( p < 0.001) than calculated intakes in both Zombwe (16.6 vs. 10.1 mg/d) and Mikalango (29.6 vs. 19.1 mg/d), attributed to some soil contaminant iron based on high Al and Ti concentrations in diet composites. A small portion of iron in acidic soil from Zombwe, but not Mikalango calcareous soil, was bioavailable, as it induced ferritin expression in the cells, and may have contributed to higher plasma ferritin and total body iron for the Zombwe women reported earlier, despite lower iron intakes. In conclusion, iron intakes calculated from food composition data were underestimated, highlighting the importance of analyzing duplicate diet composites where extraneous contaminant iron from soil is likely. Acidic contaminant soil may make a small but useful contribution to iron nutrition. [ABSTRACT FROM AUTHOR]

Peptides with in vitro antioxidant activity have no direct reaction on in vivo organisms, because of gastrointestinal (GI) barriers in human tract. In this study, low-molecular-weight peptides of casein were acquired by hydrolysis with alcalase and isolation with Sephadex G-25 gel filtration. Each peptide fraction was performed on simulated GI digestion (stage I) and Caco-2 cell absorption (stage II) for evaluating GI stability, with molecular weight distribution, peptide nitrogen, trolox equivalent antioxidant capacity, and oxygen radical antioxidant capacity. The peptide fraction below 1,000 Da (F3) had shown weaker structural stability during stage I digestion, while it exerted excellent antioxidative stability in whole stages and finally produced the highest content of GI resistant peptides. Three resistant peptides, Ile-Glu, Ser-Asp-Lys, and Ala-Tyr-Pro-Ser, were characterized, and Ala-Tyr-Pro-Ser might strongly contribute to in vivo antioxidant activities. It is suggested that alcalase may promote the production of GI resistant peptides. [ABSTRACT FROM AUTHOR]

It is well known that vitamin C is an important enhancer of nonheme iron bioavailability due to its high reducing capacity. Camu-camu, a fruit that grows in the jungle of Peru, contains high amount of vitamin C (2,780 mg per 100 g). In this study, we investigated the effect of camu-camu on nonheme iron bioavailability from two different meals (rice with lentils and wheat flour porridge) using an in vitro Caco-2 cell model. These two meals were treated with three different camu-camu juice concentrations (C0 = 0 g, C1 = typical consumption, and C2 = 3X typical consumption). The results showed that camu-camu reduced rather than enhanced nonheme iron bioavailability. The inhibiting trend was significant (p<0.0001) in the wheat flour porridge (from 124 to 91 and 35 μg ferritin/μg protein, for C0, C1 and C2, respectively). With the rice with lentils, there was no significant effect of camu-camu due to the high polyphenols and phytate contents of the meal. Relative bioavailability values obtained showed significant decrease with increasing camu-camu juice concentration for both meals. As expected, the ascorbic acid added to the meals at a concentration equivalent to that present in C2, had no effect on bioavailability with rice meal but increased significantly with wheat flour meal. The findings of this study suggest that camu-camu, in the traditional way of preparation, may significantly reduce nonheme iron bioavailability because of its high polyphenol content which overrides the beneficial effect of its high ascorbic acid content [ABSTRACT FROM AUTHOR]

Genotypic variation of iron bioavailability and the relationship between iron bioavailability and nutrient composition in polished rice among 11 rice genotypes were assessed using an in vitro digestion/Caco-2 cell model. The results indicated that significant differences in iron bioavailability were detected among tested rice genotypes, with a 3-fold range, suggesting a possibility of selecting high bioavailable iron by plant breeding. Although iron bioavailability was not significantly correlated with Fe concentration in polished rice among tested rice genotypes, the results also indicated that most of the iron dense genotypes showed relatively high ferritin formation in Caco-2 cell and transported iron. Additionally, iron bioavailability in polished rice was enhanced by addition of ascorbic acid, with a much wider range of Fe bioavailability variation in polished rice with addition of ascorbic acid than that without addition of ascorbic acid. The positive relationship between iron bioavailability in polished rice and cysteine concentration ( R = 0.669) or sulfur (S) concentration ( R = 0.744) among tested rice genotypes, suggests that cysteine and sulfur concentration in polished rice could be used as an indicator for high iron bioavailability. [ABSTRACT FROM AUTHOR]

Abstract: Glucosamine, as a dietary supplement for management of osteoarthritis, has a low and erratic oral bioavailability due to its transport-mediated absorption and presystemic loss in liver and GI tract. The present study described an effective approach to improve glucosamine intestinal absorption and hence its bioavailability using chitosan. Effects of chitosan on intestinal permeability and pharmacokinetics of glucosamine were evaluated in Caco-2 cell monolayer and rats, respectively. In addition, randomized crossover pharmacokinetic studies in beagle dogs were performed to evaluate the oral bioavailabilities of the developed glucosamine oral formulations containing chitosan (QD-Glu solution and QD-Glu tablet) in comparison to its commercial products. Caco-2 permeability studies demonstrated that chitosan could enhance the absorptive transport of glucosamine by 1.9–4.0-fold via the reversible opening of the cell tight junction. After oral administration of glucosamine solutions containing chitosan in rats, it was found that 0.5% (w/v) chitosan exhibited the highest enhancement in C max (2.8-fold) and AUC0−∞ (2.5-fold) of glucosamine. Further pharmacokinetic studies in beagle dogs demonstrated that QD-Glu solution and QD-Glu tablet showed much higher relative bioavailabilities of 313% and 186%, when comparing with Wellesse™ solution and Voltaflex™ tablet, respectively. In conclusion, chitosan could serve as a promising oral absorption enhancer for glucosamine. [Copyright &y& Elsevier]

Highlights: [•] BCRP was involved in the efflux of rhein. [•] MRP2 did not participate in the efflux of rhein. [•] P-gp did not affect the rhein transport. [ABSTRACT FROM AUTHOR]

Laportea bulbifera extract is effective in resisting inflammation and shows a good therapeutic effect on rheumatoid arthritis in rats. However, the absorption characteristics of active components in L. bulbifera extract in Caco-2 cells are still unclear, which limits the in-depth development of L. bulbifera resources. The purpose of this study was to investigate the absorption and transport mechanism of the active components of L. bulbifera extract in the Caco-2 cell model and explore the effects of different factors(concentration, time, pH value, temperature, and efflux transporter inhibitor) on its uptake and transport. The results showed that L. bulbifera extract at the concentration of 2.0-8.0 mg·mL~(-1) showed no toxicity to Caco-2 cells. The uptake and transport of L. bulbifera extract in the Caco-2 cell model were concentration-dependent and time-dependent. The main absorption mechanism was passive diffusion, and acidic condition(pH 5.0-6.0) and 37 ℃ were more favorable for drug absorption. P&#95;(app)&gt;1.0×10~(-6 )cm·s~(-1) of each component indicated that L. bulbifera was a moderately absorbed drug. P-gp, MRP2, and BCRP were not involved in its uptake and transport.

Abstract: The pot experiment grown with cabbage was conducted. The initial soil and six incubated soils with different total Cd (0.25, 0.78, 1.3, 3.18, 5.34 and 7.11mg Cd/kg soil) were used in the pot experiment. The present study was to examine cadmium (Cd) accumulation in edible parts of cabbage and its correlation with Cd concentrations in cabbage garden soil, and evaluate the bioavailability and toxicity of Cd accumulating in cabbage by a human intestinal cell culture model (Caco-2). The results showed that Cd accumulation of cabbage was linearly correlated with Cd concentration in grown soils. Cd uptake of Caco-2 cells increased gradually with increasing level of Cd accumulation in cabbage. MTT assay investigation suggested that viability of the Caco-2 cells reduced with Cd accumulation in cabbage. In comparison with the control group, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the experiment groups decreased as treated with Cd contaminated cabbages, and there was significant difference in partial groups (p < 0.05). At levels of 47.69mg Cd kg-1 accumulated in cabbage, the value of T-AOC of cells decreased significantly (p < 0.05), while the content of MDA in cells was significantly higher than that in other groups. The results suggested that Cd concentrations in the edible parts of test cabbage crops were linearly responded to the Cd levels in the growth soil, and toxicological effect of Cd to Caco-2 cells aggravated gradually with Cd accumulation increased in cabbage. [Copyright &y& Elsevier]

Abstract: A straightforward and sensitive reversed-phase high-performance liquid chromatography (HPLC) assay was developed and validated for the analysis of osthol and its phase I metabolites (internal standard: umbelliferone). The method was validated for the determination of osthol with respect to selectivity, precision, linearity, limit of detection, recovery, and stability. The linear response range was 0.47–60μM, and the average recoveries ranged from 98 to 101%. The inter-day and intra-day relative standard deviations were both less than 5%. Using this method, we showed that more than 80% of osthol was metabolized in 20min in a phase I metabolic reaction system. Transport experiments in the Caco-2 cell culture model indicated that osthol was easily absorbed with high absorptive permeability (>10×10−6 cm/s). The permeability did not display concentration-dependence or vectorial-dependence and is mildly temperature sensitive (activation energy less than 10kcal/mol), indicating passive mechanism of transport. When analyzed by LC–MS/MS, five metabolites were detected in a phase I reaction system and in the receiver side of a modified Caco-2 cell model, which was supplemented with the phase I reaction system. The major metabolites appeared to be desmethyl-osthol and multiple isomers of dehydro-osthol. In conclusion, a likely cause of poor osthol bioavailability is rapid phase I metabolism via the cytochrome P450 pathways. [Copyright &y& Elsevier]

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 ??-carotene, ??-carotene, lycopene, astaxanthin, ??-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 ??-carotene, ??-carotene and lycopene and the xanthophyll ??-cryptoxanthin were also examined and had lower uptake and secretion values when compared to lutein, zeaxanthin and astaxanthin. The xanthophyll ??-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. [ABSTRACT FROM PUBLISHER]

The aim of the present study was to investigate the influence of culture time on hPEPT1-mediated transport in Caco-2 cell monolayers. Peptide transport activity in Caco-2 cells grown in standard media and in a “rapid” 4-day model was first compared. The rapid 4-day Caco-2 cell model, cultured using a cocktail of growth factors and agonists, displayed lower peptide uptake capacity than Caco-2 cells grown for 4 days in conventional media, and was judged to be unsuitable for peptide transport studies. Peptide transport activity as well as monolayer integrity and tissue morphology were evaluated in the standard >21 days model as a function of the culture time. Peptide transport activity was studied using [14C]-glycylsarcosine ([14C]-Gly-Sar). Monolayer integrity was evaluated by transepithelial electrical resistance (TEER) measurements and [3H]-mannitol permeabilities. Tissue morphology and hPEPT1 expression were studied using confocal laser scanning microscopy (CLSM) and conventional staining/immunostaining. Caco-2 cells grown in conventional media became confluent after 3–4 days. Mannitol permeability decreased from day 5 to 21 and TEER increased steadily until ∼day 21. Apical hPEPT1 uptake activity appeared to be maximal in cells cultured for >21 days, whereas basolateral uptake reached a maximum already after 12 days in culture. In some of the passages studied, a secondary increase in hPEPT1 transport activity was observed in cells grown for >25 days. A large carrier-mediated transepithelial peptide flux component was evident from day 14. [Copyright &y& Elsevier]

In traditional Chinese Medicine, Rehmannia glutinosa (Gaertn.) DC., as the principle herb of ShengDiHuang Decotion (SDHD), has the effect of cooling blood and hemostasis, and tonifying the yin and kidney. Rheum L., as adjuvant herbs, assist Rehmannia glutinosa (Gaertn.) DC. to promote blood circulation to remove blood stasis. To study the mechanism of Rhein (RH) involved in the promotion of Rehmannioside D (RD) absorption by pharmacokinetic studies, single-pass intestinal perfusion, Caco-2 cell models, molecular docking technique and western blotting. Initially, the intestinal absorption of RD in the presence or absence of RH was conducted through pharmacokinetic studies. Thereafter, the intestinal absorption of RD and RH was studied using the single-pass intestinal perfusion and Caco-2 cell models. Finally, using molecular docking technique and western blotting. We found that the promotion of RD absorption by RH was mediated by breast cancer resistance and multidrug resistance-associated protein 2, thereby affecting the permeability of the intestinal epithelium. Additionally, RH and RD can competitively bind to breast cancer resistance and multidrug resistance-associated protein 2, and that RH inhibits the expression of breast cancer resistance and multidrug resistance-associated protein 2 in the ileum to promote the intestinal absorption of RD. This study reveals the mechanisms associated with the RH-mediated promotion of RD absorption and provides a basis for further exploring the synergistic effect of Rehmannia glutinosa (Gaertn.) DC and rhubarb. [Display omitted] [ABSTRACT FROM AUTHOR]

In vitro and in situ experimental models that are descriptive of drug absorption in vivo are valuable tools in the discovery of new chemical entities that are bioavailable after oral administration. The specific objective of the study was to compare the intestinal permeabilities obtained in the three absorption models for consistency, and to assess the utility of the models in predicting the fraction of dose absorbed in human studies. The intestinal absorption models that were compared are widely used: the rat in situ single-pass intestinal perfusion system, the rat everted intestinal ring method, and monolayers of human colon adenocarcinoma cell line (CACO-2). The models were compared using small molecular reference compounds, as well as a series of peptidomimetic (PM) analogs. Each model had strong potential for estimating the fraction absorbed. For small organic molecules, excellent correlation was observed when permeabilities from CACO-2 cells and perfusions, or everted rings and perfusions, were compared. Weaker correlation was observed between everted rings and CACO-2 cells. Permeabilities for the set of reference compounds and PMs were positively correlated between any two of the three systems. Variance between correlations for reference compounds and PMs are likely due to structural features and physicochemical properties that are unique to the latter class of compounds. The results support caution in extrapolating correlations based on findings with small organic molecules to the behavior of complex peptidomimetics. Corroboration of permeabilities with two methods of determination is a useful cross-validation of experimental systems, as well as producing a reliable permeability assessment. CACO-2 cell monolayers and rat single-pass intestinal perfusion combine the highest correlation between systems, most defined relationship with fraction absorbed in humans, and experimental logistics in-line with discovery candidates. [ABSTRACT FROM AUTHOR]

• 16 trace elements were studied in black, green, white and mate ready-to-drink ice teas. • Al, Cu, Sr, Mn and Zn bioaccessibility corresponded to 40–60% of their total content in ice tea samples. • 12% PTWI for Al can be reached for children by a daily intake of one glass of black tea. • Mate and black ice teas are sources of manganese and selenium (values above 15% DRI). Tea is one of the most consumed non-alcoholic beverages in world and it has been frequently associated to health benefits. Besides its nutrient composition, non-essential trace elements associated with toxic effects may also be present. Ever since food components undergo biotransformation process along gastrointestinal tract after ingestion, it is important to evaluate both total and bioavailable content of trace elements. Therefore, this study aimed to provide comprehensive data concerning the influence of the in vitro digestion on sixteen trace elements present in ready-to-drink ice tea (black, green, mate and white tea). Essential minerals (Co, Cr, Cu, Fe, Mn, Se and Zn) and inorganic contaminants (Al, As, Cd, Li, Ni, Pb, Sb, Sn and Sr) contents were determined by ICP OES after microwave acid digestion. Bioaccessibility evaluation was carried out by simulating the gastric (pepsin) and intestinal juice (pancreatin and bile salts) and bioavailability used Caco-2 cells culture as an intestinal epithelial model. Moreover, tannins were evaluated by UV–VIS spectroscopy. Multivariate analysis allowed classifying ice tea samples in three groups, based on their trace elements profile. Al, Cu, Sr, Mn and Zn bioaccessible fractions corresponded to, approximately, 40–60% of their total content. For Mn, bioaccessibility and bioavailability presented the same pattern (green ice tea > black ice tea > mate ice tea) whilst Sr bioavailability in green tea were 50% higher than in black tea samples. [ABSTRACT FROM AUTHOR]

Background: Flavonoid compounds are one kind of active ingredients isolated from a traditional Chinese herb Zizyphi spinosae semen (ZSS). Studies have shown that ZSS flavonoids have significant antioxidant effects., Methods: In this study, the Caco-2 cell monolayer model was constructed to investigate the intestinal absorption characteristics and mechanism of Isovitexin (IV), Swertisin (ST), Isovitexin-2''-O-β-D-glucopyranoside (IVG), Spinosin (S), 6'''-p-coumaroylspinosin (6-CS) and 6'''-feruloylspinosin (6-FS)., Results: The results of the bidirectional transport assay showed that the six flavonoids have good intestinal absorption in a near-neutral and 37°C environment, and the absorbability in descending order was 6-FS>6- CS>IVG>S>IV>ST. The results of carrier inhibition experiments and transport kinetics indicated that the absorption mechanism of six flavonoids was energy-dependent monocarboxylate transporter (MCT)-mediated active transport. In particular, the para-cellular pathway also participated in the transport of IV, ST, IVG and S. Furthermore, the efflux process of six flavonoids was mediated by P-glycoprotein (P-gp) and multidrug resistance protein (MRP), which may result in a decrease of bioavailability., Conclusion: Our findings provide significant information for revealing the relationship between the intestinal absorption mechanism of flavonoids and its structure as well as laying a basis for the research of flavonoid preparations., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The everted gut sacs and Caco-2 cell models were used to investigate the intestinal absorptive characteristics and subcellular localization of chitobiose and chitopentaose in this study. In everted gut sacs, the absorptive pattern showed no concentration-dependent manner when the concentration was lower than 10 mM. In the presence of phlorizin (100 μM) and phloretin (100 μM), the chitobiose absorption rates decreased by (4.97 ± 0.89)% and (19.2 ± 2.77)%, and they were (10.4 ± 2.43)% and (27.5 ± 1.68)% for chitopentaose. In Caco-2 cells, the concentration showed influences similar to those with the everted gut sacs results. After adding phlorizin and phloretin in the apical side, the P appAP-BL of chitobiose and chitopentaose significantly decreased. Considering the translocation, they were enriched in endoplasmic reticulum and mitochondrion. This study indicated that concentration and active transporter were capable of mediating the absorption of chitobiose and chitopentaose, and the subcellular localization of them could help to study the mechanisms of their effects.

There is a high demand for functional meat products due to increasing concern about food and health. In this work, Zn and Se bioavailability was increased in chicken meat emulsions that are enriched with Hydroxytyrosol (HXT), a phenolic compound obtained from olive leaf. Six different chicken emulsions were elaborated. Three were made with broiler chicken meat supplemented with inorganic Zn and Se: control, one with HXT (50 ppm) added and one with HXT (50 ppm) and Extra Virgin Olive Oil (EVOO) (9.5%) added; and, three were made with chicken meat from chickens fed a diet that was supplemented with organic Zn and Se: control, one with HXT (50 ppm) added and one with HXT (50 ppm) and EVOO (9.5%) added. The samples were digested in vitro and the percent decomposition of phenolic compounds was measured by HPLC. Mineral availability (Fe, Zn and Se) was measured by cell culture of the Caco-2 cell line and the results were compared with mineral standards (Fe, Zn, and Se). The data obtained showed that neither HXT resistance to digestion nor Fe availability was affected by the presence of organic Zn and Se or phenolic compounds. Zn uptake increased in the presence of HXT, but not when its organic form was used, while Se uptake increased but it was not affected by the presence of HXT. It was concluded that the enrichment of meat—endogenously with organic minerals and exogenously with phenolic compounds—could be considered an interesting strategy for future research and applications in the current meat industry. [ABSTRACT FROM AUTHOR]

The objective of the present study is to determine the effect of phytic acid (PA), sodium oxalate (SO) and sodium silicate (SS) on non-heme iron bioavailability in both the presence and absence of ascorbic acid (AA) using an in vitro digestion/Caco-2 cell model, and the levels of AA needed to promote Fe absorption from Fe complexed with PA, SO or SS were also determined. The results indicated that adding PA at 1:1, 3:1, 5:1 and 10:1 molar as compared to Fe decreased ferrous iron uptake by 55.80 %(P < 0.05), 72.33 % (P < 0.05), 73.32 % (P < 0.05), and 73.26 % (P < 0.05), respectively. Adding SS at 1:1, 3:1, 5:1 and 10:1 molar as compared to Fe also decreased ferrous iron uptake by 51.40 % (P < 0.05), 66.12 %(P < 0.05), 60.19 % (P < 0.05) and 45.11 % (P < 0.05), respectively. Adding SO at 5:1 and 10:1 molar as compared to Fe decreased ferrous iron uptake by 40.81 % (P < 0.05) and 33.14 % (P < 0.05), respectively. When adding AA to iron plus organic acid medias reached molar ratios of 5:5:1 AA:PA:Fe, 3:5:1 AA:SO:Fe and 5:5:1 AA:SS:Fe, iron absorption from FeSO4 were significantly increased (P < 0.05). However, no significant effect was observed in iron absorption from FeCl3 when adding AA to the media. The results showed that PA, SS or SO decreases iron uptake from ferrous Fe, and AA can counteract their inhibiting effect on ferrous iron absorption and thus increase ferrous iron uptake. The results may be important for elucidating factors affecting iron bioavailability in the small intestine and for the development of foods with improved iron bioavailability.

The transport mechanism of fructosazine, a glucosamine self-condensation product, was investigated using a Caco-2 cell model. Fructosazine transport was assessed by measuring the bidirectional permeability coefficient across Caco-2 cells. The mechanism of transport was evaluated using phlorizin, an inhibitor of sodium-dependent glucose cotransporters (SGLT) 1 and 2, phloretin and quercetin, inhibitors of glucose transporters (GLUT) 1 and 2, transcytosis inhibitor wortmannin, and gap junction disruptor cytochalasin D. The role of hexose transporters was further studied using downregulated or overexpressed cell lines. The apparent permeability (P a,b ) of fructosazine was 1.30 ± 0.02 × 10 -6 cm/s. No significant (p > 0.05) effect was observed in fructosazine transport by adding wortmannin and cytochalasin D. The presence of phlorizin, phloretin, and quercetin decreased fructosazine transport. The downregulated GLUT cells line was unable to transport fructosazine. In human intestinal epithelial Caco-2 cells, GLUT1 or GLUT2 and SGLT are mainly responsible for fructosazine transport.