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
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生物化学
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DOI
PubMed
高影响因子
CHEMICAL RESEARCH IN CHINESE UNIVERSITIES
·
2014
·Vol. 30
·期 5
·731-737
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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
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DOI
高影响因子
Food Frontiers
·
2024
·
IF 7.4
Ziyi Han,Leyu Wang,Panjie Sun,Mengxin Huang,Fei Yu,Junsheng Liu,Yuanyuan Wu,Puming He,Youying Tu,Bo Li
Hyperglycemia and diabetes are common metabolic disorders. It is considered a safe and effective strategy to screen active ingredients from food and herbs for controlling blood sugar levels. Quinic acid (QA) is a natural polyphenolic acid with various health-promoting properties. In this study, QA was found to exhibit a potent inhibitory effect on α-glucosidase activity, with a half maximal inhibitory concentration (IC 50 ) of 5.46 mM. This inhibitory property surpassed that of three common organic acids including gallic acid, malic acid, and citric acid. A combination of 25% acarbose (0.5 mM) and 75% QA (5 mM) (v/v) exhibited synergistic inhibition of α-glucosidase activity. Enzyme kinetics, fluorescence spectra, and molecular docking analyses indicated that QA acted as an uncompetitive inhibitor of α-glucosidase, with hydrogen bonds playing a key role in the intermolecular interactions. Moreover, QA was found to effectively inhibit three major nonenzymatic glycation products including advanced glycosylation end products (AGEs), fructosamine, and α-dicarbonyl in a dose-dependent manner, outperforming the positive control aminoguanidine (AG) within the tested concentration range. Utilizing a Caco-2 cell model, QA demonstrated the ability to inhibit the transmembrane absorption of glucose. This study highlighted QA as a promising food functional factor that had been overlooked in the past, offering potential benefits in improving hyperglycemia, diabetes, and associated complications through the inhibition of α-glucosidase, nonenzymatic glycosylation, and glucose uptake.
研究领域:
食品科学
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分子生物学
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代谢疾病研究
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DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2018
·
IF 3.412
Lujia Li,Qingxue Fu,Mengxin Xia,Lei Xin,Hongyi Shen,Guowen Li,Guang Ji,Qianchao Meng,Yan Xie
Phytic acid (IP6) is a natural phosphorylated inositol, which is abundantly present in most cereal grains and seeds. This study investigated the effects of IP6 regulation on P-glycoprotein (P-gp) and its potential mechanisms using in situ and in vitro models. The effective permeability of the typical P-gp substrate rhodamine 123 (R123) in colon was significantly increased from (1.69 ± 0.22) × 10–5 cm/s in the control group to (3.39 ± 0.417) × 10–5 cm/s (p < 0.01) in the 3.5 mM IP6 group. Additionally, IP6 can concentration-dependently decrease the R123 efflux ratio in both Caco-2 and MDCK II-MDR1 cell monolayers and increase intracellular R123 accumulation in Caco-2 cells. Furthermore, IP6 noncompetitively inhibited P-gp by impacting R123 efflux kinetics. The noncompetitive inhibition of P-gp by IP6 was likely due to decreases in P-gp ATPase activity and P-gp molecular conformational changes induced by IP6. In summary, IP6 is a promising P-gp inhibitor candidate.
研究领域:
药理学
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细胞生物学
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药物递送
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产品关联
DOI
PubMed
高影响因子
BioNanoScience
·
2025
·Vol. 15
·期 2
·1-12
·
IF 3.2
Liang Tisong,Jing Pu
The poor stability of chlorophyll has inhibited its application in food industry. Our previous study showed that the stability of chlorophyll can be enhanced by incorporating with sodium caseinate (NaCas). This present work further explored the characteristics of NaCas–chlorophyll dispersion in simulated gastrointestinal digestion and its inhibitory effects on human epithelial colorectal adenocarcinoma cells (Caco-2 cells). Results indicated that the gastrointestinal digestion resulted in alterations to the physical appearance of the NaCas–chlorophyll dispersion. Fourier-transform infrared spectroscopy illustrated that the second structure of NaCas underwent alterations during gastrointestinal digestion. Morphological observation revealed that the digested NaCas–chlorophyll dispersion exhibited granular morphology with smaller particle size. The Caco-2 cells exposed to digested NaCas–chlorophyll dispersion exhibited decreased viability and destroyed mitochondrial structure, which may be related to the enhanced absorptivity of the NaCas–chlorophyll dispersion following gastrointestinal digestion. These findings provided theoretical basis for understanding the characteristics changes and biological activity of NaCas–chlorophyll dispersion during gastrointestinal digestion.
研究领域:
食品科学
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生物化学
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营养学
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产品关联
DOI
高影响因子
Foods
·
2025
·Vol. 14
·期 9
·1594
·
IF 5.1
Jihao Zeng,Xue Bai,Yongli Zhang,Qianyu Le,Jinhong Wu,Huiyun Chen
To develop a highly bioavailable calcium supplement, this study utilized Peruvian squid ( Dosidicus gigas ) skin as a raw material. Through alkaline protease hydrolysis and enzymatic membrane reactor separation, three molecular weight fractions of squid skin peptides were obtained, followed by calcium ion chelation to synthesize calcium-chelating peptides (CCPs-SS). Systematic characterization revealed that the less than 1 kDa fraction of CCPs-SS exhibited superior antioxidant capacity (82.18%) and calcium chelation efficiency (77.14%) in cellular models compared to higher molecular weight counterparts. Optimal synthesis conditions were identified as 60 °C, pH 9, and 12 mg/mL calcium chloride concentration. Post-chelation analyses demonstrated significant physicochemical alterations for CCPs-SS: ζ-potential shifted from −18.4 mV to −10.47 mV, while particle size increased from 476.75 nm to 664.4 nm. Notably, membrane separation enhanced phenylalanine and leucine molar concentrations by 25.5% and 57.6%, respectively, suggesting structural modifications that potentiate bioactivity. These findings demonstrate an innovative strategy for converting squid processing byproducts into functional nutraceuticals, which not only addresses calcium deficiency challenges but also promotes resource sustainability by utilizing waste materials.
研究领域:
食品科学
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营养学
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生物化学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS
·
2018
·Vol. 44
·期 2
·295-303
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IF 1.362
Xu Renjie,Peng Ying,Wang Mengyue,Li Xiaobo
Background Isoalantolactone and alantolactone are the main sesquiterpene lactones in Radix Inulae (dried root of Inula helenium L. or I. racemosa Hook. F.), which is a frequently utilized herbal medicine. They also occur in several plants and have various pharmacologic effects. However, they have been found to have poor oral bioavailability in rats. Objectives To understand the intestinal absorptive characteristics of isoalantolactone and alantolactone as well specific influx and efflux transporters in their absorption. Methods Bidirectional permeabilities of isoalantolactone and alantolactone were investigated across Caco-2 cell monolayers. Transport assays were performed using different concentrations of two lactones and specific inhibitors of ATP-binding cassette transporters and influx transporters. Results The absorption permeability of isoalantolactone and alantolactone was high at the tested concentrations (5, 20 and 80 μmol/l), and the major permeation mechanism of both lactones was found to be passive diffusion with active efflux mediated by multidrug resistance-associated proteins (MRPs) and breast cancer resistance protein (BCRP). Conclusion Our results demonstrated that the absorption permeability of isoalantolactone and alantolactone was good in the Caco-2 cell model. The isoalantolactone and alantolactone absorption elucidated in this study provides useful information for further pharmacokinetics studies. Since low intestinal absorption can now be ruled out as a cause, further studies are needed to explain the low oral bioavailability of the two sesquiterpene lactones.
研究领域:
药理学
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中药学
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生物医学
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产品关联
DOI
PubMed
高影响因子
IET Nanobiotechnology
·
2018
·Vol. 12
·期 7
·946-950
·
IF 2.059
Zhuanzhuan Zhang,Xianjun Dai
The conditions were optimised for preparing Alginate oligosaccharide (AOS) nanoliposomes, and Caco-2 cell experiments were carried out to examine their antitumour effects. The optimal formulation of AOS nanoliposomes was as follows: a phosphatidylcholine-to-cholesterol ratio of 5.12, AOS concentration of 8.44 mg/mL, Tween 80 concentration of 1.11%, and organic phase to aqueous phase ratio of 5.25. Under the above conditions, the experimental encapsulation efficiency was 65.84%, and the AOS nanoliposomes exhibited a small particle size of 323 nm. After Caco-2 cells were treated with AOS liposomes and AOS for 24 h, AOS nanoliposomes inhibited the growth of Caco-2 cells to a greater extent than AOS at concentrations of 0.0625, 0.125, 0.25, 0.5 and 1 mg/mL ( P < 0.01). LDH leakage exhibited a concentration-dependent increase following treatment with 0.5-1 mg/mL AOS nanoliposomes, and the inhibitory effect of AOS nanoliposomes exhibited a more significant difference than AOS ( P < 0.01). Cells treated with 0.5 mg/mL and 1 mg/mL AOS nanoliposomes displayed a substantial and significant increase in activity compared with AOS ( P < 0.01). Based on these results, AOS nanoliposomes exerted a more significant effect on inhibiting Caco-2 cell proliferation than AOS.
研究领域:
药剂学
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肿瘤学
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细胞生物学
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产品关联
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
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细胞生物学
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产品关联
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
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分子生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2021
·
IF 6.953
Fei Li,Yunlu Wei,Jing Zhao,Guoyong Yu,Linlin Huang,Quanhong Li
Pumpkin polysaccharides with various bioactivities are mainly taken orally, thus detailed knowledge of the intestinal transport of which are essential for understanding its bioactivities. The Caco-2 cells monolayer model (mimic intestinal epithelium) was successfully constructed and Cucurbia moschata polysaccharides (PPc-F) were successfully conjugated with fluorescein isothiocyanate (FITC) to evaluate the transcellular transport mechanism and subcellular localization of PPc. The transport process of PPc-F was energy-dependent, and a moderately-absorbed biological macromolecule according to the apparent permeability coefficients (P app ) value. The endocytosis process of PPc-F in Caco-2 cells included the clathrin- and caveolae (or lipid draft)-medicated routes. And the translocation process was related to endoplasmic reticulum (ER), golgi apparatus (GA), tubulin and the acidification of endosomes. As for the intracellular location of PPc-F, it was mainly accumulated in ER. The study provided an understanding of the transmembrane transport of PPc-F, and could help studying the mechanisms of its effects.
研究领域:
药理学
·
分子生物学
·
营养科学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2019
·
IF 2.983
Chengcan Lu,Kejia Fu,Kangna Cao,Jiali Wei,Jing Zhou,Di Zhao,Ning Li,Yang Lu,Xijing Chen,Yongjie Zhang
A rapid and sensitive ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was applied to investigate the permeability characteristics and transport mechanism of trihexyphenidyl hydrochloride (TH) in D-hanks with the Caco-2 cells model. Analytes were separated using an Zorbax Extend-Agilent C 18 (1.8 μm, 4.6 × 30 mm) column following a simple methanol precipitation treatment. The mobile phase consisted of methanol and water containing 0.1% formic acid, and the total gradient program time was 1.5 min. Method validation results showed TH was linear in 2–500 ng/mL (r 2 > 0.99), and the lower limit of quantification (LLOQ) was 2 μg/mL. The intra-run and inter-run precision (coefficient of variation, CV) was within 2.80%, and the accuracy (relative error, RE) was within ±11.10%. Stability of TH was evaluated in different storage conditions, including short-term I-III, long-term I-III, 2 and 4 h in the artificial gastrointestinal tract, respectively. There was no obvious interference between TH and internal standards (IS). With the established Caco-2 monolayer permeability model, Papp(AB) of TH was calculated as 46.29 ± 8.31 × 10 −6 cm/s, and the efflux ratio (ER) value was calculated as 0.22, indicating a high permeability character of TH. The transmembrane transport of TH followed the concentration-dependent, temperature-independent, and energy-free manner. Collectively, these characteristics indicate that TH is a highly permeable drug and the transport mechanism is mainly via passive diffusion.
研究领域:
药理学
·
药物代谢动力学
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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）