FOOD RESEARCH INTERNATIONAL
·
2022
·
IF 7.425
Shaoying Gong,Jiachen Zheng,Junjie Zhang,Yucong Wang,Zhixin Xie,Yubao Wang,Jianchun Han
Intestinal epithelial barrier dysfunction can cause several intestinal diseases. Flavonoids have been shown to be beneficial to the intestinal epithelial barrier function. However, the effects of taxifolin (TAX), a naturally occurring flavonoid, on the intestinal epithelial barrier function are unclear. Thus, the aims of this study were to investigate the protective effect and potential mechanism of TAX against lipopolysaccharide (LPS)-induced intestinal epithelial barrier dysfunction in a Caco-2 cell monolayer model. Our results showed that TAX increased the transepithelial electrical resistance (TEER) and decreased the fluorescein isothiocyanate (FITC)-dextran (4 kDa) flux in the damaged intestinal epithelial barrier. Meanwhile, TAX inhibited an LPS-induced decrease in mRNA and protein expression of tight junction (TJ) proteins (claudin-1, zonula occludens [ZO]-1, and occludin), and ameliorating the continuous distribution pattern disrupted of TJs. These results suggested that TAX ameliorated intestinal epithelial barrier dysfunction. Regarding the underlying mechanism, TAX reduced the LPS-induced secretion of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in Caco-2 cell monolayers. In addition, TAX suppressed the phosphorylation of nuclear factor kappa-B (NF-κB), inhibitor protein of NF-κBα (IκBα), and myosin light chain (MLC), and downregulated the expression of myosin light chain kinase (MLCK) in LPS-treated Caco-2 cells. In summary, TAX can maintain TJ proteins by inhibiting the NF-κB/MLCK pathway and pro-inflammatory factor secretion to ameliorate LPS-induced intestinal epithelial barrier dysfunction. Thus, TAX is a promising candidate agent for use in functional food to ameliorate intestinal barrier dysfunction.
研究领域:
药理学
·
细胞生物学
·
胃肠病学
·
免疫学
✓ 已验证
DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
·
2017
·
IF 1.74
Yinghao Wang,Heshan Wang,Shuisheng Wu,Desen Li,Sainan Chen
Gelsemium elegans (GE) is a kind of well-known toxic plant. It can be detoxified by Mussaenda pubescens (MP), but the detoxification mechanism is still unclear. Thus, a detoxification herbal formula (GM) comprising GE and MP was derived. The Caco-2 cells monolayer model was used to evaluate GM effects on transporting six kinds of indole alkaloids of GE. The bidirectional transport studies demonstrated that absorbance percentage of indole alkaloids in GE increased linearly over time. But in GM, Papp (AP→BL) values of the most toxic members, gelsenicine, humantenidine, and gelsevirine, were lower than that of Papp (BL→AP) (). The prominent analgesic effect members, gelsemine and koumine, were approximately 1.00 in values. Nowhere was this increasing efflux more pronounced than in the case of indole alkaloids with N-O structure. In the presence of verapamil, the values of humantenidine, gelsenicine, gelsevirine, and humantenine were decreased by 43.69, 41.42, 36.00, and 8.90 percent, respectively. The values in presence of ciclosporin were homologous with a decrease of 42.32, 40.59, 34.00, and 15.07 percent. It suggested that the efflux transport was affected by transporters. Taken together, due to the efflux transporters participation, the increasing efflux of indole alkaloids from GM was found in Caco-2 cells.
研究领域:
药理学
·
毒理学
·
中药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2019
·
IF 2.606
Xia Yan,Shuqing Cao,Ying Li,Pei Xiao,Zipeng Huang,Haiyan Li,Yan Ma
Curcumin (Cur) and its nanomedicine were researched in Caco-2 cells to investigate the internalization and subcellular transport across Caco-2 cell monolayer membrane. Cur loaded polymer micelle (PM), nanoemulsion (NE) and liposome (Lipo) were prepared to explore the transport process incorporating endocytosis, intracellular trafficking and transcytosis in Caco-2 cells. Firstly, nanocarriers could contribute to the cellular uptake and improve the stability of Cur within the Caco-2 cells. The co-mediation of clathrin , lipid raft/caveolae and/or macropinocytosis were involved in the internalization of Cur nanopreparations, indicating the diversity and partial energy-dependency of the endocytosis. Secondly, the endocytosed nanocarriers with Cur successively transported from apical early endosome to late endosome with the extension of incubation time . Furthermore, the intracellular location of Cur nanomedicines in lysosome and endoplasmic reticulum (ER) were detected and illustrated the actual transport of Cur nanomedicine to lysosome and ER. Finally, nanocarriers could enhance the transcytosis of Cur, involving the energy-dependent patterns. Especially, Cur-PM exhibited more advantages in regulating and coordinating the entry and the exit of Cur. The study indicated that the coexistence of multiple transport pathways had the potency to promote nanocarriers transcytosis and provided a rational dosage design for oral Cur.
研究领域:
药学
·
纳米技术
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细胞生物学
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
Food Bioscience
·
2023
·
IF 5.2
Cheng-Hai Yan,Xiao-Meng Xun,Richard A. Herman,Yu-Fan Zhan,Lu-Chan Gong,Fu-An Wu,Jun Wang
Silkworm pupae oil (SPO) was regarded as a good alternative to alpha-linolenic acid supplements, which contain a variety of triacylglyceride with high nutritional value . To investigate the connections between triacylglyceride composition and lipid gastrointestinal digestive absorption profiles, isolation and bioavailability of triacylglyceride monomers from silkworm pupae oil was analyzed. In this study, two triacylglyceride monomers rich in α -linolenic acid were separated by preparative liquid chromatography , namely LnLnLn (1,2,3- α -linolenic acid triacylglyceride) and LnLnL (1,2- α -linolenic acid, 3- linoleic acid triacylglyceride). The in vitro digestion in the pH-stat model results showed the digestive rate of LnLnLn was 0.4101 ± 0.0089 s −1 , which was significantly higher than that of SPO (0.2494 ± 0.0108 s −1 ) ( p < 0.05). The in vitro absorption in the Caco-2 cells model results showed the absorptivity of LnLnLn and LnLnL were 6.40 ± 0.19% and 6.06 ± 0.54%, which were significantly higher than SPO (5.43 ± 0.51%) ( p < 0.05). In addition, the mRNA expression levels of lipid metabolism-related proteins provide evidence for the absorption superiority of LnLnLn and LnLnL. The present work provides novel structural lipids for rapid and efficient supplementation of α -linolenic acid.
研究领域:
营养学
·
生物化学
✓ 已验证
产品关联
DOI
高影响因子
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
·
2024
·
IF 4.2
Fangfang Ding,Huimei Wang,Yingzhi Li,Xueping Leng,Jiaming Gao,Danfei Huang
Due to the massive production and use of plastic, the chronic and evolving exposure to microplastics in our daily lives is omnipresent. Nonylphenol (NP), a persistent organic pollutant, may change toxicity when it co-exists with microplastics. In this study, polystyrene microplastics (PS-MPs), either alone or with pre-absorbed NP, generated oxidative stress and inflammatory lesions to Caco-2 cells, as well as affecting proliferation via the MAPK signaling pathway and causing apoptosis. Damage to cell membrane integrity and intestinal barrier (marked by lower transepithelial electric resistance, greater bypass transport, and tight junction structural changes) leads to enhanced internalization risk of PS-MPs. Some important intestinal functions including nutrient absorption and xenobiotic protection were also harmed. It is worth noting that the exposure of PS-MPs with a diameter of 0.1 μm improved intestinal functions quickly but acted as a chemosensitizer for a long time, inhibiting cell perception of other toxic substances and making the cells more vulnerable.
研究领域:
环境科学
·
毒理学
·
细胞生物学
·
胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2018
·
IF 3.412
Fei Zhou,Weisu Huang,Maiquan Li,Yongheng Zhong,Mengmeng Wang,Baiyi Lu
Acteoside and salidroside are major phenylethanoid glycosides (PhGs) in Osmanthus fragrans Lour. flowers with extensive pharmacological activities and poor oral bioavailability. The absorption mechanisms of these two compounds remain unclear. This study aimed to investigate the bioaccessibility of these compounds using an in vitro gastrointestinal digestion model and to examine the absorption and transport mechanisms of PhGs using the Caco-2 cell model. The in vitro digestion model revealed that the bioaccessibility of salidroside (98.7 ± 1.35%) was higher than that of acteoside (50.1 ± 3.04%), and the superior bioaccessibility of salidroside can be attributed to its stability. The absorption percentages of total phenylethanoid glycoside, salidroside, and acteoside were 1.42–1.54%, 2.10–2.68%, and 0.461–0.698% in the Caco-2 model, respectively. Salidroside permeated Caco-2 cell monolayers through passive diffusion. At the concentration of 200 μg/mL, the apparent permeability (Papp) of salidroside in the basolateral (BL)-to-apical (AP) direction was 23.7 ± 1.33 × 10–7 cm/s, which was 1.09-fold of that in the AP-to-BL direction (21.7 ± 1.38 × 10–7 cm/s). Acteoside was poorly absorbed with low Papp (AP to BL) (4.75 ± 0.251 × 10–7 cm/s), and its permeation mechanism was passive diffusion with active efflux mediated by P-glycoprotein (P-gp). This study clarified the bioaccessibility, absorption, and transport mechanisms of PhGs. It also demonstrated that the low bioavailability of acteoside might be attributed to its poor bioaccessibility, low absorption, and P-gp efflux transporter.
研究领域:
药理学
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营养科学
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细胞生物学
·
食品化学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2021
·
IF 5.279
Yang Xu,Yuting Li,Jiahong Xie,Lianghua Xie,Jianling Mo,Wei Chen
The present study is aimed to clarify the absorption and metabolism properties of pelargonidin-based anthocyanins. Results showed that pelargonidin-3-O-rutinoside (Pg3R) was absorbed in its intact form after oral administration and reached a maximum plasma concentration of 175.38 ± 55.95 nM at 60 min. Three main metabolites were identified in plasma, including Pg3R-monoglucuronide (m/z 755.2046), Pg3R-hydroxylated (m/z 595.1644), and Pg3R-demethylated (m/z 565.1569) metabolites. The plasma concentration of the Pg3R-demethylated metabolite (57.04 ± 23.15 nM) was much higher than that of other two metabolites, indicating that demethylation was the main metabolic pathway for Pg3R, while the glucuronide conjugate was detected as the dominant metabolic form of pelargonidin-3-O-glucoside (Pg3G). The bioavailability of Pg3R (1.13%) was fourfold higher than that of Pg3G (0.28%), demonstrating that anthocyanins linked to the rutinoside may exhibit higher bioavailability than that of glucoside. In vitro transport study unveiled that passive diffusion and active efflux were involved in the absorption of Pg3R and Pg3G.
研究领域:
药理学
·
营养学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Ocean University of China
·
2022
·Vol. 21
·期 3
·782-788
·
IF 1.179
Zhang Pengpeng,Zhang Miaomiao,Dong Kaiyu,Zhang Yicong,Yang Shuang,Wang Yuanhong,Jiang Tingfu,Yu Mingming,Lv Zhihua
Chito-oligosaccharide (COS) had shown a variety of biological activities and potential biomedical implications. The present study investigated the pharmacokinetics, bioavailability, and in vitro absorption of COS with degrees of polymerization (DPs) 2–7 and explored the influence of DPs on them. From Caco-2 cell permeation studies, COS were low permeability compounds with no directional effects, suggesting a low in vivo absorption mediated by facilitation diffusion and paracellular absorption. After an intragastrical administration to rats, COS2 showed the highest systemic exposure in six oligosaccharides. The bioavailability of COS2–7 was 7.33%, 6.11%, 4.67%, 4.13%, 4.02%, 0.99%, respectively. Differences in bioavailability for each COS correlated to structural variations, with high DPs contributing to a decrease in bioavailability. In conclusion, COS could be absorbed by the intestinal tract both in vitro and in vivo . The very low oral bioavailability of COS could be due to low permeability. DPs can affect absorption and bioavailability of COS2–7. This study provided evidence for the absorption characteristics of COS2–7 to help us better understanding the pharmacological actions.
研究领域:
药理学
·
生物医学科学
·
药学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2023
·
IF 6.1
Nan Li,Ruiyan Wang,Zeyuan Deng,Jianqun Zhou,Wenwen Li,Qian Du,Liufeng Zheng
Sucrose emerges as a metal-ion chelating agent with excellent stability that may increase metal-ion absorption. This study aimed to characterize the structure of zinc–sucrose complex and investigate its ability to promote zinc absorption in Caco-2 monolayer cells and mice. Based on the results of the inductively coupled plasma emission spectrometer (ICP-ES), scanning electron microscopy–energy-dispersive X-ray spectroscopy (SEM-EDX), and Fourier transform infrared spectroscopy (FT-IR), it can be inferred that zinc and sucrose were chelated at a 1:1 ratio, with the hydroxyl groups playing a significant role. The Caco-2 monolayer cell model revealed that zinc–sucrose complex increased the amount of zinc uptake, retention, and transport in a dose- and time-dependent manner. Through the upregulation of genes and proteins for ZIP4, MT1, and DMT1, treatment with zinc–sucrose complex improved the proportion of absorbed zinc utilized for transport compared to ZnCl2 (26.21 ± 4.96 versus 8.50 ± 1.51%). Pharmacokinetic analysis of mice confirmed the zinc absorption-promoting effect of zinc–sucrose complex, as indicated by the considerably higher serum zinc level (4.16 ± 0.53 versus 2.56 ± 0.45 mg/L) and intestinal ZIP4, MT1, and DMT1 gene expression than ZnCl2. Further treatment of different zinc channel inhibitors and CETSA demonstrated the direct interaction of zinc–sucrose complex with ZIP4 protein and ZIP4-mediated cellular transport of zinc–sucrose complex. These findings provide a novel insight into the zinc absorption-promoting mechanism of zinc–sucrose complex, which could be used as an ingredient in functional foods to treat zinc deficiency.
研究领域:
营养学
·
药理学
·
分子生物学
·
细胞生物学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2020
·Vol. 12
·期 2
·167
·
IF 4.421
Yu Wang,Xu Bai,Bo Hu,Maochen Xing,Qi Cao,Aiguo Ji,Shuliang Song
Detailed knowledge of the intestinal transport of polymannuronic acid (PM) and polyguluronic acid (PG) is critical for understanding their biological activities. To investigate the transport in the gastrointestinal tract, PM and PG were chemically modified with tyramine and conjugated with fluorescein isothiocyanate (FITC) to synthesize FITC-PM (F-PM) and FITC-PG (F-PG) successfully. The transport mechanisms of F-PM and F-PG across the intestinal epithelial cell monolayers (Caco-2 cell monolayers) were then investigated. The results demonstrated that the transport of F-PM and F-PG into epithelial cells was time- and energy-dependent, which was mediated by the macropinocytosis pathway and the clathrin- and caveolae (or lipid raft)-mediated endocytic pathway. The transport process of F-PM and F-PG in Caco-2 cells depended on the acidification of endosomes and involved lysosomes. Tubulin mediated the transport of F-PM, but not of F-PG. Moreover, the absorption enhancer chitosan (CS) promoted the transport of F-PM and F-PG, increasing the apparent permeability coefficient (Papp) by 1.9-fold and 2.6-fold, respectively, by reversibly opening the tight junction (TJ). In summary, this study provided a comprehensive understanding of the transport of PM and PG in the small intestinal epithelial cells, which will provide a theoretical basis for the development of PM and PG with good intestinal absorption.Keywords:polymannuronic acid;polyguluronic acid;transport mechanisms;Caco-2 cell monolayers
研究领域:
药理学
·
生物药剂学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Wang Mengting,Mao Haiguang,Ke Zhijian,Wang Jinbo
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 100 μg/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 (5 mM glucose) and simulated-fed (25 mM 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.
研究领域:
药理学
·
营养学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2022
·
IF 9.231
Yi Wu,Minhua Zong,Zhenhui Zhang,Yongtai Wu,Lin Li,Xia Zhang,Hong Wu,Bing Li
Advanced glycation end-products (AGEs) are a chemically heterogeneous set of modifications widely found in processed foods. Due to uncertain bioavailability, dietary AGEs regulate energy homeostasis through mechanisms that largely remain unclear. In this study, selective transmembrane transport of AGEs with different modification types from glycated β-casein digest were identified and compared. The results showed that only a few types of free and peptide-bound AGEs can easily cross the Caco-2 monolayers and thus exert their effects. A combination of biochemical assays, mitochondrial analyses, and comparative experiments identified that the effect of AGEs on cellular energy homeostasis comes mainly from their free fractions. Mechanistically, free AGEs arrest the mitochondrial differentiation and mtDNA repair by intervening in the function of thymidine phosphorylase, and interfering with mitochondrial energy production by inhibiting the activation of AMPK-SIRT6 signaling pathway. These results demonstrate mechanisms by which processed foods cause mitochondrial dysfunction and lead to dysfunctional energy homeostasis.
研究领域:
营养学
·
细胞生物学
·
代谢学
·
食品科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）