JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2020
·
IF 3.209
Baolin Wang,Yimeng Lu,Rong Wang,Shumeng Liu,Xiaolong Hu,Hao Wang
Amentoflavone, a kind of biflavonoid existing in several medicinal plants such as Selaginella moellendorfi and Gingko biloba , possesses anti-inflammatory, antioxidant, anti-virus, anti-tumor activities. In the present study, a new reliable and sensitive UHPLC-ESI-MS/MS method was developed to determine the permeability of amentoflavone under different conditions, and its metabolites in Caco-2 cells were identified by means of UHPLC-Q-TOF-MS/MS method. The results showed that amentoflavone could be considered as a compound with moderate intestinal absorption in Caco-2 cell model and its absorption characteristics might be involved in paracellular passive penetration and clathrin-mediated endocytosis with no participation of efflux transporters. Eight metabolites of amentoflavone were identified in Caco-2 cell model, indicating that the main metabolic pathways were oxidation, reduction, methylation and glucuronide conjugation. This study can provide valuable evidence for an in-depth understanding of absorption mechanism and transformation of amentoflavone in the intestine.
研究领域:
药理学
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分析化学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2014
·
IF 2.61
Jingze Duan,Yan Xie,Huilin Luo,Guowen Li,Tao Wu,Tong Zhang
Flavonoid isorhamnetin occurs in various plants and herbs, and demonstrates various biological effects in humans. This work will clarify the isorhamnetin absorption mechanism using the Caco-2 monolayer cell model. The isorhamnetin transport characteristics at different concentrations, pHs, temperatures, tight junctions and potential transporters were systemically investigated. Isorhamnetin was poorly absorbed by both passive diffusion and active transport mechanisms. Both trans- and paracellular pathways were involved during isorhamnetin transport. Active transport under an ATP-dependent transport mechanism was mediated by the organic anion transporting peptide (OATP); isorhamnetin’s permeability from the apical to the basolateral side significantly decreased after estrone-3-sulfate was added ( p < 0.01). Efflux transporters, P-glycoproteins (P-gp), breast cancer resistance proteins (BCRP) and multidrug resistance proteins (MRPs) participated in the isorhamnetin transport process. Among them, the MRPs (especially MRP2) were the main efflux transporters for isorhamnetin; transport from the apical to the basolateral side increased 10.8-fold after adding an MRP inhibitor (MK571). This study details isorhamnetin’s cellular transport and elaborates isorhamnetin’s absorption mechanisms to provide a foundation for further studies.
研究领域:
药理学
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生物化学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2021
·
IF 5.279
Ritian Jin,Jiaqi Shang,Xiangyu Teng,Ligang Zhang,Minhe Liao,Jiaxin Kang,Ran Meng,Dangfeng Wang,Haowei Ren,Ning Liu
Here, we characterize the activities of two depeptidyl peptidase-IV (DPP-IV) inhibitory peptides, VLATSGPG and LDKVFER, using the Caco-2 monolayer model for the intestine. VLATSGPG and LDKVFR inhibited the DPP-IV in the cells via a mixed-type inhibition mode, with in situ IC50 values of 207.3 and 148.5 μM, respectively. Furthermore, VLATSGPG and LDKVFR were transported intact across the cells, with Papp values of 2.41 ± 0.16 and 4.23 ± 0.29 × 10–7 cm/s, respectively. Fragmented peptides were identified in the basolateral side of the membrane. Two of these, GPG and VLA, exhibited high inhibitory activities of 83.6 ± 3.3 and 58.5 ± 2.5%, respectively, at 100 μM concentration. Although 3 mM VLATSGPG and LDKVFR were transported across the epithelium in a concentration-dependent manner, their transport did not damage the tight junction proteins, ZO-1 and occludin. This study demonstrates that the two peptides potentially regulate DPP-IV activity in the intestine.
研究领域:
生物化学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NanoImpact
·
2025
·
IF 5.5
Yuan-Yuan Liu,Jie Liu,Yuan Guo,Qiangqiang Zhang,Aoneng Cao,Haifang Wang
Nanoplastics enter the human body mainly by ingestion through the gastrointestinal tract and thus the uptake and release of nanoplastics in intestinal cells have been studied. However, the fate of nanoplastics in intestinal cells remains poorly understood, particularly how they are exocytosed. Herein, we investigated the uptake, distribution, and exocytosis of nanoplastics in Caco-2 cells using 70 nm red fluorescent polystyrene (R70PS) as a nanoplastic model. The results show that R70PS readily enters Caco-2 cells and the content per cell peaks at around 24 h, but the total intracellular content in all cells increases continuously over 72 h. In addition, the uptake mechanisms change over incubation time, i.e. R70PS entered Caco-2 cells via both the energy-independent pathway and the energy-dependent caveolae-mediated endocytosis and macropinocytosis at 4 h incubation, but almost all R70PS entered cells in an energy-dependent manner via caveolae-mediated endocytosis, macropinocytosis, and clathrin-mediated endocytosis at 12 h incubation. Most of the intracellular R70PS accumulated in lysosomes, but R70PS also entered the mitochondria and its level increased over time. Approximately 45 % of the intracellular R70PS could be cleared from the cells within 12 h, mainly via the lysosomal pathway. Exocytosis was also associated with autophagy and was facilitated by the increase in the number of mitochondria and lysosomes, but inhibited by serum in the medium. Our findings deepen the understanding of the interaction between nanoplastics and intestinal cells, which is helpful for the risk assessment of nanoplastics.
研究领域:
生物学
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医学
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL RESEARCH IN CHINESE UNIVERSITIES
·
2014
·Vol. 30
·期 5
·731-737
·
IF 1.119
Ma Jingwei,Kan Hong,Ma Yinghui,Men Lihui,Pi Zifeng,Liu Zhiqiang,Liu Zhongying
Ultra performance liquid chromatographic-electrospray ionization-mass spectrometry(UPLC-ESI-MS) was used to investigate the potential interaction between selected ingredients of Aconitum and fritillary. The efflux ratios of 14-benzoylmesaconine(BM), 14-benzoylaconine(BC), 14-benzoylhypaconine(BH), mesaconitine(MA), aconitine( AC) and hypaconitine(HA) was 11.16, 12.53, 11.69, 12.8, 11.03 and 6.15, respectively, and the secretion of them was inhibited by Verapamil, which means they are the substrates of permeability-glycoprotein(P-gp). The transport of Aconitum alkaloids extract through a Caco-2 cell monolayer was determined in the absence and presence of fritillary extract. And the fritillary extract increased the absorption of Aconitum alkaloids. Peimine(PE) and peiminine( PEN) in fritillary increased the absorption of pure Aconitum alkaloids. The transport of digoxin was respectively enhanced by PE and PEN, which means they are the inhibitors of P-gp. PEN showed more effective inhibition than PE at the same concentration. The in vitro data suggest that the compounds such as fritillary present in alkaloids were able to inhibit the P-gp activity and lead modifying the transport of alkaloids.
研究领域:
药理学
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中药学
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生物化学
✓ 已验证
产品关联
DOI
高影响因子
POULTRY SCIENCE
·
2025
·
IF 4.2
Yuxin Shao,Yipu Li,Shuxian Xie,Bo Zhang,Jing Li,Yalei Wang,Yusheng Gao,Jianyuan Ma,Tenghe Ma,Zheng Wang
This study aimed to evaluate the effects of 4-hydroxyphenylacetic acid ( 4-HPAA ), a phenolic acid compound from Yucca schidigera extract, in Caco-2 cells and artificial rearing of pigeons. In vitro experiments showed that 4-HPAA at different levels exhibited higher cell viability than shikimic acid and 3,4-dihydroxybenzoic acid, and with the highest viability observed at 600 μM. Additionally, 600 μM 4-HPAA alleviated LPS-induced upregulation of IL-1β and CASPASE1 expressions ( P < 0.05) . In vivo results demonstrated that supplemental 4-HPAA at 500, 1000, and 2000 mg/kg levels did not affect the body weight of 25-day-old pigeons ( P > 0.05), but all levels increased immunoglobulin G ( IgG ) and IgM levels ( P < 0.05). Compared with control, 2000 mg/kg 4-HPAA significantly reduced serum L-lactic acid, D-lactic acid and lactate dehydrogenase ( LDH ) activity ( P < 0.05); increased spleen and bursa of Fabricius indices and intestinal total antioxidant capacity activity of 25-day-old pigeons ( P < 0.05); and elevated ileal barrier-related genes ( OCCLUDIN, CLAUDIN1 and MUC2) in 7-day-old pigeons, as well as jejunal MUC2 and ileal OCCLUDIN in 25-day-old meat pigeons ( P < 0.05). It also inhibited glycolytic gene hexokinase 2 expression, while upregulating the signaling pathway genes CAMK2G and MKNK1 ( P < 0.05). Supplemental 500 and 1000 mg/kg 4-HPAA significantly increased serum total cholesterol levels ( P < 0.05). Notably, 500 mg/kg 4-HPAA had an adverse effect on intestinal integrity, as indicated by the highest serum diamine oxidase content, and increased glycolytic gene LDH-B expression; However, it enhanced microbial richness and diversity in the intestines of 7-day-old pigeon ( P < 0.05). Besides, 1000 mg/kg 4-HPAA impaired intestinal morphology, as evidenced by a lower ileal villus height-to-crypt depth ratio ( P < 0.05), but resulted in the highest abundance of Lactococcus in 25-day-old pigeons. In conclusion, 600 μM 4-HPAA exhibits anti-inflammatory activity in Caco-2 cells, and 2000 mg/kg 4-HPAA promotes immune function and intestinal barrier integrity while inhibiting glycolytic gene expression and the production of related serum metabolites in meat pigeons.
研究领域:
兽医学
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营养学
·
分子生物学
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动物科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2025
·
IF 9.8
Ruihong Dong,Yuting Wang,David Julian McClements,Qiang Yu,Jianhua Xie,Huijie Zhang,Lizhi Huang,Bin Li,Jinlong Tian,Yi Chen
This study investigated intestinal absorption and cellular antioxidant efficacy of anthocyanin (ACN)-loaded ovalbumin (OVA)-carrageenans (ι-, λC)/dextran sulfate (DS) nanocomplexes. Utilizing Caco-2 cells, we assessed endocytic pathways, intracellular trafficking, and delivery efficacy of ternary nanocomplexes. ACN-loaded nanocomplexes could be internalized by cells in a time-, dose-, energy-dependent manner, with macropinocytosis, lipid raft/caveolae, and actin co-mediated endocytosis routes playing pivotal roles. Nanocomplexes inhibited P-glycoprotein efflux of Rhodamine-123, enhancing the apparent permeability of ACN into cells, especially for OVA-ιC-ACN. Transport pathways of ACN-loaded nanocomplexes through Caco-2 monolayers involved different organelles including microtubules, Golgi complexes, endoplasmic reticulum, and lysosomes. Compared to free ACN, nanocomplexes exhibited more efficiency in recovering cellular viability and endogenous antioxidant enzyme activities under oxidative stress. Our findings provide a more comprehensive understanding of internalization, transport mechanisms of protein-polysaccharide-anthocyanin nanocomplexes across epithelial cell monolayers, and provide valuable insights for designing efficient ACN-loaded nanocomplex systems with high transportation efficiency and intestinal absorption.
研究领域:
生物化学
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药剂学
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细胞生物学
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营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
·
2025
·
IF 3.5
Lijun Su,Zhipeng Yu,Wenzhu Zhao
BACKGROUND This study aimed to elucidate the transport mechanism of lycopene-loaded nanomicelles to improve intestinal absorption of lycopene. The interactive mechanism between lycopene and nanomicelles was investigated through isothermal titration calorimetry (ITC). The cytotoxicity, cellular uptake, endocytosis, and intracellular transport pathways of lycopene-loaded nanomicelles were investigated using the Caco-2 cell model. RESULTS The ITC results demonstrated that nanomicelles/lycopene binding was an entropy-driven spontaneous exothermic reaction, and hydrophobic interactions were the main driving force. Lycopene-loaded nanomicelles were not cytotoxic, and uptake of lycopene by Caco-2 cells increased 2.20-fold after nanoencapsulation. The results of intracellular transport of lycopene-loaded nanomicelles indicated that the endoplasmic reticulum, Golgi apparatus, and lysosomes play key roles in this process. The intracellular transport results showed that the endoplasmic reticulum, Golgi apparatus, and lysosomes were important organelles for intracellular transport of lycopene-loaded nanomicelles. CONCLUSION Nanomicelles effectively enhance the cellular uptake of lycopene and are promising carriers for its delivery. This study contributes to the understanding of the transport mechanism of nanomicelles through intestinal epithelial cells. © 2025 Society of Chemical Industry.
研究领域:
营养学
·
生物化学
·
药剂学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULES
·
2022
·Vol. 27
·期 4
·1230
·
IF 4.927
Li Jiang,Yanling Xiong,Yu Tu,Wentong Zhang,Qiyun Zhang,Peng Nie,Xiaojun Yan,Hongning Liu,Ronghua Liu,Guoliang Xu
Puerarin (PUR) and gastrodin (GAS) are often used in combined way for treating diseases caused by microcirculation disorders. The current study aimed to investigate the absorption and transportation mechanism of PUR and GAS and their interaction via Caco-2 monolayer cell model. In this work, the concentration in Caco-2 cell of PUR and GAS was determined by HPLC method. The bidirectional transport of PUR and GAS and the inhibition of drug efflux including verapamil and cyclosporine on the transport of these two components were studied. The mutual influence between PUR and GAS, especially the effect of the latter on the former of the bidirectional transport were also investigated. The transport of 50 μg·mL−1PUR in Caco-2 cells has no obvious directionality. While the transport of 100 and 200 μg·mL−1PUR presents a strong directionality, and this directionality can be inhibited by verapamil and cyclosporine. When PUR and GAS were used in combination, GAS could increase the absorption of PUR while PUR had no obvious influence on GAS. Therefore, the compatibility of PUR and GAS is reasonable, and GAS can promote the transmembrane transport of PUR, the effect of which is similar to that of verapamil.Keywords:transport mechanism;puerarin;gastrodin;absorption;Caco-2 cell monolayer
研究领域:
药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MACROMOLECULAR BIOSCIENCE
·
2014
·Vol. 14
·期 6
·842-852
·
IF 3.65
Yan Zhang,Xuli Du,Yu Zhang,Guofei Li,Cuifang Cai,Jinghua Xu,Xing Tang
This work deals with the synthesis of insulin loaded nanoparticles (NPs) composed of thiolated Eudragit L100 (Eul-cys) and reduced glutathione (GSH) as potential nanocarriers for oral delivery of insulin. Perfectly spherical NPs with an average particle size of nearly 200–300 nm are prepared. The insulin release from Eul-cys/GSH and Eul-cys NPs in PBS (pH 7.4) shows that GSH can slightly decrease the release rate of insulin. Eul-cys in combination with GSH or sodium caprate (SC) is evaluated for its permeation enhancing effect of FITC-insulin using the Caco-2 monolayer and Caco-2/HT29-MTX co-cultured cells models. SC results in greater permeation enhancement compared to GSH. However, GSH proves to be less toxic. Paracellular transport of insulin represents the main mechanism by which the NPs facilitate insulin permeation through the intestinal epithelium, whereas a number of NPs are also taken up by the cells and release insulin within the cells.
研究领域:
药剂学
·
生物医学工程
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Haiyong Pan,Bai Miao,Wenting Zheng,Lina Yang,He Liu
Polysaccharides derived from soybean seed coats exhibit diverse functional properties and significant application potential; however, their intestinal absorption and transport mechanisms remain poorly understood. This study investigates the molecular docking interactions of two soybean seed coat polysaccharides (NMSP and CSSP), extracted using different methods, with the MUC2 protein, and explores their absorption and transport properties using Caco-2 cell models. Molecular dynamics simulations revealed the binding modes and key interaction sites between NMSP, CSSP, and the MUC2 protein. A Caco-2 monolayer model was established to evaluate polysaccharide uptake and transport under varying concentrations, temperatures, and pH conditions. The results demonstrated that the absorption of both polysaccharides was time- and concentration-dependent, while transport analyses revealed that both NMSP and CSSP could traverse the Caco-2 cells, primarily via endocytic pathways. In terms of apparent permeability (Papp) and transport rate, CSSP exhibited moderate absorption, whereas NMSP was classified as poorly absorbed. Moreover, acidic conditions significantly enhanced the transport rates of both polysaccharides. This study provides critical insights into the absorption and transport characteristics of soybean seed coat polysaccharides, offering a theoretical foundation for further exploration of their bioavailability and physiological functions.
研究领域:
食品科学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Marine Drugs
·
2021
·Vol. 19
·期 2
·92
·
IF 5.118
Yue Sui,Yue Gu,Yujing Lu,Chenxu Yu,Jie Zheng,Hang Qi
Fucoxanthin (FX), a natural carotenoid found in seaweed with multiple functional activities, is unstable with a poor water solubility that limits its utilization. This study aimed to improve FX’s stability and bioavailability via the nano-encapsulation of FX in polyvinylpyrrolidone (PVP)-coated[email protected]nanoparticles (NPs). The[email protected]NPs were evaluated in terms of their morphology, stability, encapsulation efficiency (EE), loading capacity (LC), and in vitro release to optimize the encapsulation parameters, and a 1:8 FX:PVP ratio was found to perform the best with the highest EE (85.50 ± 0.19%) and LC (10.68 ± 0.15%) and improved FX stability. In addition, the[email protected]NPs were shown to effectively deliver FX into Caco-2 cancer cells, and the accumulation of FX in these cancer cells showed pro-oxidative activities to ameliorate H2O2-induced damage and cell death. The[email protected]NPs could potentially become a new therapeutical approach for targeted cancer treatment.Keywords:fucoxanthin;nanoparticles;Caco-2 cells;pro-oxidation;targeted cell death
研究领域:
药学
·
癌症研究
·
纳米技术
✓ 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）