FOOD AND CHEMICAL TOXICOLOGY
·
2020
·
IF 4.679
Fei Zhou,Weisu Huang,Tao Xu,Lipeng Wu,Qi Chen,Jiyu Peng,Xin Liu,Baiyi Lu
Acteoside is one of the most widespread phenylethanoid glycosides with pharmacological activities , including antioxidant, neuroprotective property, etc. However, its bioavailability is poor due to the low absorption and P-gp efflux. This study aimed to select food derived P-gp inhibitors for promoting the acteoside absorption and investigate whether the inhibitors could increase the bioavailability and stability of acteoside. Results showed that EGCG and quercetin significantly decreased the BL-to-AP efflux and promoted the AP-to-BL influx of acteoside across Caco-2 monolayers with optimum concentrations of 320 μM EGCG or 240 μM quercetin adding to 320 μM acteoside. EGCG increased the bioavailability of acteoside to 1.43-fold, but quercetin had no such effect. Further study showed that EGCG and quercetin had no effects on the storage and digestion stability of acteoside. This work revealed that EGCG could improve the acteoside absorption across the Caco-2 monolayers and enhance the bioavailability of acteoside in rats.
研究领域:
药理学
·
营养保健品
·
药物递送
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
·
2021
·Vol. 53
·期 11
·1459-1468
·
IF 3.848
Tao Huaping,Bao Zhiwei,Fu Zhengwei,Jin Yuanxiang
The widespread use of chlorothalonil (CTL) has caused environmental residues and food contamination. Although the intestinal epithelial barrier (IEB) is directly involved in the metabolism and transportation of various exogenous compounds, there are few studies on the toxic effects of these compounds on the structure and function of IEB. The disassembly of tight junction (TJ) is a major cause of intestinal barrier dysfunction under exogenous compounds intake, but the precise mechanisms are not well understood. Here, we used Caco-2 cell monolayers as an in vitro model of human IEB to evaluate the toxicity of CTL exposure on the structure and function of IEB. Results showed that CTL exposure increased the paracellular permeability of the monolayers and downregulated mRNA levels of the TJ genes (ZO-1, OCLN, and CLDN1), polarity marker gene (SI), and anti-apoptosis gene (BCL-2) but upregulated the mRNA levels of apoptosis-related genes, including BAD, BAX, CASP3, and CASP8. Western blot analysis and immunofluorescence assay results showed the decreased levels and disrupted distribution of TJ protein network, including ZO-1 and CLDN1 in CTL-exposed IEB. In addition, the accumulation of intracellular reactive oxygen species, decreased mitochondrial membrane potential, and increased active CASP3 expression were observed in treated IEB. The result of TUNEL assay further confirmed the occurrence of cell apoptosis after CTL exposure. In addition, the phosphorylation of mitogen-activated protein kinases, including ERK, JNK and p38, was increased in CTL-exposed IEB. In summary, our results demonstrated that CTL exposure induced IEB dysfunction in Caco-2 cell monolayers by activating the mitogen-activated protein kinase pathway.
研究领域:
毒理学
·
细胞生物学
·
分子生物学
·
环境科学
✓ 已验证
DOI
PubMed
高影响因子
PLoS One
·
2020
·Vol. 15
·期 5
·e0227844
·
IF 2.74
Renjie Xu,Hongdan Zhu,Lingmin Hu,Beimeng Yu,Xiaohua Zhan,Yichu Yuan,Ping Zhou
Morroniside is a biologically active polyphenol found in Cornus officinalis Sieb . et Zucc (CO) that exhibits a broad spectrum of pharmacological activities, such as protecting nerves, and preventing diabetic liver damage and renal damage. However, little data are available regarding the mechanism of its intestinal absorption. Here, an in vitro human intestinal epithelial cell model of cultured Caco-2 cells was applied to study the absorption and transport of morroniside. The effects of donor concentration, pH and inhibitors were investigated. The bidirectional permeability of morroniside from the apical (AP) to the basolateral (BL) side and in the reverse direction was studied. When administered at three tested concentrations (5, 25 and 100 μM), the apparent permeability coefficient (P app ) values in the AP-to-BL direction ranged from 1.59 × 10 −6 to 2.66 × 10 −6 cm/s. In the reverse direction, BL-to-AP, the value was ranged from 2.67 × 10 −6 to 4.10 × 10 −6 cm/s. The data indicated that morroniside transport was pH-dependent. The permeability of morroniside was affected by treatment with various inhibitors, such as multidrug resistance protein inhibitors MK571 and indomethacin, as well as the breast cancer resistance protein inhibitor apigenin. The mechanisms of the intestinal absorption of morroniside may involve multiple transport pathways, such as the passive diffusion and efflux protein-mediated active transport especially involving multidrug resistance protein 2 and breast cancer resistance protein. After the addition of CO, the P app values in the AP-to-BL direction increased significantly, therefore, it can be assumed that some ingredients in the CO promote morroniside absorption in the small intestine.
研究领域:
药理学
·
肠道吸收机制
·
天然产物研究
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Yanan Zhao,Bin Li,Jiang Liu,Lei Chen,Hui Teng
The potential of natural phytochemicals in addressing ethanol-related public safety concerns has been garnering attention. Galangin, a potent flavonoid renowned for its antioxidative and anti-inflammatory characteristics, is derived from the galanga plant, and propolis is derived from bees. Here, we documented the effects of galangin on ethanol-stimulated intestinal tight junction damage and investigated its potential protective mechanism in both in vivo and in vitro models, which has not been extensively investigated. Our results revealed that galangin efficaciously mitigated ethanol-induced intestine injury and dysfunction of the intestinal barrier. Concurrently, galangin significantly counteracted the ethanol-induced upregulation of NLRP3 inflammasome-associated proteins and activated the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) signaling pathways in both the mouse colon and Caco-2 cells. Interestingly, similar to galangin, inhibitors of MAPKs and the NF-κB p65 reduced ethanol-induced NLRP3 inflammasome activation and intestinal tight junction damage. To sum up, our results showed that galangin blocks the ethanol-induced perturbation of the intestinal barrier and activation of the NLRP3 inflammasome via the NF-κB/MAPK signaling pathways.
研究领域:
药理学
·
胃肠病学
·
免疫学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Science and Human Wellness
·
2024
·
IF 5.6
Wen Nie,Feiran Xu,Kai Zhou,Jieying Deng,Ying Wang,Baocai Xu
The study evaluated the stability of an oligopeptide (Lys-Arg-Gln-Lys-Tyr-Asp, KRQKYD) and its transport mechanism by simulating gastrointestinal digestion and a model of human intestinal Caco-2 monolayer cells in vitro . In this study, the effects of environmental factors (temperature, pH and NaCl concentration) and simulated gastrointestinal digestion on the stability of KRQKYD were evaluated by indicators of the levels of alanine transaminase (ALT), aspartate transaminase (AST) and malondialdehyde (MDA) in an alcohol-induced hepatocyte injury model. The results showed that KRQKYD still maintained satisfactory hepatocyte-protective activity after treatment with different temperatures (20−80 °C), pH (3.0−9.0), NaCl concentration (1 %−7 %) and simulated gastrointestinal digestion, which indicated that KRQKYD showed good stability to environmental factors and simulated gastrointestinal digestion. Furthermore, the intact KRQKYD could be absorbed in a model of Caco-2 monolayer cells with a P app value of (9.70 ± 0.53) × 10 −7 cm/s. Pretreatment with an energy inhibitor (sodium azide), a competitive peptide transporter inhibitor (Gly-Pro) and a transcytosis inhibitor wortmannin did not decrease the level of transepithelial KRQKYD transport, indicating that the transport mechanism of KRQKYD was not associated with energy dependent, vector mediated and endocytosis. The tight junction disruptor cytochalasin D significantly increased the level of transepithelial KRQKYD transport ( P < 0.05), suggesting that intact KRQKYD was absorbed by paracellular transport.
研究领域:
药理学
·
细胞生物学
·
胃肠病学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF NANOPARTICLE RESEARCH
·
2014
·Vol. 16
·期 4
·1-16
·
IF 2.278
Lian He,Zhang Tianhong,Sun Jin,Pu Xiaohui,Tang Yilin,Zhang Youxi,He Zhonggui
The aim of this study was to evaluate the underlying mechanism of enhanced oral absorption of paclitaxel (PTX)-loaded chitosan–vitamin E succinate– N -acetyl- l -cysteine (CS–VES–NAC) nanomicelles from the cellular level. In aqueous solution, CS–VES–NAC copolymer self-assembled into the polymeric nanomicelles, with the size ranging from 190 to 240 nm and the drug loading content as high as 20.5 %. Cytotoxicity results showed that the PTX-loaded nanomicelles exhibited the similar effect to PTX solution (PTX-Sol) on Caco-2 cells, but no toxicity observed for blank CS–VES–NAC nanomicelles. The cellular uptake of PTX was significantly increased by CS–VES–NAC nanomicelles, compared with that of PTX-Sol, due to the possible escapement of P-glycoprotein (P-gp) efflux pumps by endocytosis pathway. Confocal laser scanning microscope (CLSM) images also confirmed CS–VES–NAC nanomicelles could be effectively internalized by Caco-2 cells. More importantly, P
app value of PTX-loaded CS–VES–NAC nanomicelles was 2.3-fold higher than that of PTX-Sol, and the efflux ratio decreased by more than 10.8-fold for the nanomicelles. As a consequence of opening of tight junctions and P-gp inhibition induced by free CS–VES–NAC copolymer, the P
app value of PTX was almost increased up to 19.5-fold. All the results indicate that CS–VES–NAC copolymer hold great promises as nanocarrier for antitumor drug oral delivery by improving paracellular and transcellular permeation.
研究领域:
药剂学
·
生物医学工程
·
药物代谢动力学
✓ 已验证
产品关联
DOI
高影响因子
FOOD CHEMISTRY
·
2024
·
IF 8.5
Jie Sheng,Mahmoud Youssef,Hongshan Liang,Jing Li,Bin Li
Improving sea buckthorn flavonoids (SF) stability and bioacccessibility is of more practical significance for evaluating the total bioacccessibility of such foods. Therefore, we prepared nanoparticles using zein and gum Arabic (GA) by anti-solvent precipitation to encapsulate SF. Nanoparticles were characterized and assessed for their effect on the stability, release, bioaccessibility, absorption, and antioxidant properties of SF in the in vitro digestion and cell line. The uniform, regular nanoparticles achieved 77.19 % encapsulation efficiency. The SF retention rates during long-term storage (60.46 %) and in vitro digestion (53.76 %) demonstrated that nanoparticles exhibited good stability and bioaccessibility compared to free SF. Furthermore, cellular absorption, the free radical scavenging rate for ABTS (85.26 %) and DPPH (80.48 %), as well as inhibitory effects on intracellular ROS further demonstrated that bilayer nanoparticles could successfully protect and exert biological characteristics of SF. This study evaluated the overall bioaccessibility of sea buckthorn flavonoids using a nanoparticle delivery system, which holds even greater significance for guiding the development of this category of natural foods.
研究领域:
食品科学
·
营养学
·
药理学
·
生物技术
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Li Li,Mingjie Xia,Lina Yang,Yutang He,He Liu,Mengxi Xie,Miao Yu
Polysaccharides impact intestinal fermentation and regulate interfacial properties which affect absorption and transportation. Short-chain fatty acids (SCFAs), the main metabolites of soy hull polysaccharide lysate, are readily absorbed by the body and perform various physiological functions. We analysed the interfacial properties and transport of soy hull polysaccharide-derived SCFAs in the Caco-2 cell model to clarify the transmembrane transport mechanism. The results showed that the interfacial properties of the co-culture system were influenced by both transit time and concentration of SCFAs, the uptake and transit rates of SCFAs at 1–3 h increased significantly with time ( P < 0.05). With increasing transit time and concentration, the transit rates of SCFAs on the apical side (AP) → basolateral side (BL) and BL → AP sides increased and then stabilised, the transit rate of the AP → BL side was higher than that of the BL → AP side. Proteomic analysis showed that soy hull polysaccharide-derived SCFAs resulted in the differential expression of 285 upregulated and 501 downregulated after translocation across Caco-2 cells. The differentially expressed proteins were mainly enriched in ribosomes, oxidative phosphorylation, nuclear transport, and SNARE vesicular transport. This study lays the theoretical foundation for understanding the structure-activity relationship of soy hull polysaccharides in the intestine.
研究领域:
营养学
·
胃肠病学
·
分子生物学
·
细胞生物学
·
蛋白质组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2020
·
IF 6.793
Huaping Tao,Zhiwei Bao,Cuiyuan Jin,Wenyu Miao,Zhengwei Fu,Yuanxiang Jin
Fungicides , usually refer to the chemical agents that can effectively control or kill the pathogenic microorganisms . Here, we revealed the effects of three different fungicides, imazalil (IMZ), chlorothalonil (CTL) and carbendazim (CBZ), which are typical broad-spectrum fungicides that are detected at high levels in the natural environment, on heterogeneous human epithelial colorectal cells (Caco-2 cells). All three fungicides had the potential to induce different degrees of toxicity, cause apoptosis, reactive oxygen species (ROS) and even change the cell cycle in the cells. The half maximal inhibitory concentration (IC50) of CTL is the lowest among these three fungicides, suggesting that it may have the highest exposure risk, followed by IMZ, and CBZ. The results of the real-time PCR, Western blotting, and mitochondrial membrane potential (MMP) assays and the activities of key enzymes suggested that CTL induced apoptosis in Caco-2 cells via a mitochondrial-dependent pathway, as indicated by the upregulation of the expression of the apoptotic p53 and bax genes, the increase of the apoptosis marker cytochrome-c, the decrease of mRNA level of bcl-2 gene, and the decrease in the MMP. Exposure to two other fungicides also upregulated the transcriptional level of bax and the expression of cytochrome- c , but the mRNA level of bcl-2 was increased (IMZ) or unchanged (CBZ), suggesting that other pathways may be involved in the induction of cellular apoptosis by these two fungicides. In addition, all three of the fungicides could induce oxidative stress in Caco-2 cells. Our data showed that the three different kinds of fungicides all caused toxic effects in Caco-2 cells through various pathways.
研究领域:
毒理学
·
细胞生物学
·
环境科学
✓ 已验证
产品关联
DOI
高影响因子
ACS Omega
·
2024
·
IF 3.7
Rui Wang,Chaolong Rao,Qiuyan Liu,Xiong Liu
Zanthoxylum alkylamides, as a numbing substance in Zanthoxylum bungeanum has many physiological effects. However, the numbing taste and unstable properties limited its application. This study aimed to optimize the preparation process of Zanthoxylum alkylamides liposomes by response surface methodology (RSM) and to investigate the in vitro absorption characteristics of the liposomes through the Caco-2 cell monolayer model. The process parameters of liposomes were as follows: Zanthoxylum alkylamides was 15 mg, phospholipid–feedstock ratio was 6.14, phospholipid–cholesterol ratio was 8.51, sodium cholate was 33.80 mg, isopropyl myristate was 29.49 mg, and the theoretical encapsulation efficiency of the prepared liposomes could reach 90.23%. Further, the particle size of the liposomes was 155.47 ± 3.16 nm, and the ζ-potential was −34.11 ± 4.34 mV. Meanwhile, the liposomes could be preserved for 14 days under the condition that the content of Zanthoxylum alkylamides was less than 2 mg/mL and the preservation temperature was lower than 25 °C. Moreover, the uptake characteristics of the Zanthoxylum alkylamides liposomes in the Caco-2 cell monolayer model were also investigated. The results showed that the Zanthoxylum alkylamides liposomes could be taken up and absorbed by Caco-2 cells. Also, the Zanthoxylum alkylamides liposomes had a better uptake performance than the unembedded Zanthoxylum alkylamides and conformed to the passive uptake.
研究领域:
药学
·
药物递送系统
·
生物药剂学
·
药代动力学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2020
·Vol. 11
·期 4
·3741-3748
·
IF 4.171
Wei Li,Mingbo Gao,Ting Han
Impairment of the intestinal barrier often occurs in inflammatory bowel diseases, and pro-inflammatory factors play a vital role in the pathogenesis of intestinal diseases. In our study, the potential protective effects of Lycium barbarum polysaccharides (LBP) against intestinal barrier dysfunction evoked by pro-inflammatory factors and its anti-inflammatory effects were investigated. Caco-2 cells were stimulated with or without tumor necrosis factor (TNF)-α in the presence or absence of LBP. Our findings showed that LBP assuaged the increase of paracellular permeability and the decrease of transepithelial electrical resistance (TER) in Caco-2 cells. In addition, LBP also prevented the secretion of pro-inflammatory markers (IL-8, IL-6, ICAM-1 and MCP-1) in TNF-α-challenged Caco-2 cells. Moreover, LBP inhibited the overexpression of tight junction (TJ) proteins (claudin-1, ZO-3, and occludin) and the increase of MLCK, pMLC, p-IκBα and NFκBp65 protein expression evoked by TNF-α was suppressed by LBP pre-incubation. This finding indicated that LBP improve TNF-α-evoked intestinal barrier dysfunction via suppressing the MLCK-MLC signaling pathway mediated by NFκB.
研究领域:
药理学
·
胃肠病学
·
细胞生物学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2024
·
IF 8.5
Jianing Fu,Shaobo Li,Meizhen Xu,Ling Liu,Li Chen,Dequan Zhang
Soup is an important presence in diet, but its absorption and transport mechanism by the human body remains unclear. In this study, Caco-2 intact cell and monolayer cell models were constructed to simulate small intestine absorption on colloidal nanoparticles (CNPs) isolated from lamb soup. The intracellular localization of CNPs was viewed by laser confocal microscopy (LSCM). CNPs uptake and release pathways were explored by differences in CNPs concentrations in 5 endocytosis inhibitor models and 4 exocytosis inhibitor models. Results indicated that CNPs endocytosis by Caco-2 cells was restrained by Nystatin and Cytochalasin D, with exocytosis being inhibited by Nocodazole and Monensin. Therefore, the major absorption pathways for CNPs were caveolin-dependent endocytosis, macropinocytosis and phagocytosis. The major transport pathways were microtubule-vesicle-mediated protein transport to the membrane and transportation between the Golgi apparatus and membrane. This study may provide theoretical support for the transport mechanism of soup products in the small intestine.
研究领域:
营养学
·
食品科学
·
细胞生物学
·
药学
✓ 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）