Food & Function
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2018
·Vol. 9
·期 4
·2251-2260
·
IF 3.289
Guo Liu,Shengwei Sun,Baoyan Guo,Benchun Miao,Zhen Luo,Zumeng Xia,Danyang Ying,Fei Liu,Bin Guo,Jian Tang,Yong Cao,Jianyin Miao
Casein phosphopeptides (CPPs) have been demonstrated to be calcium chelators. Unfortunately, few studies have been reported on the effects of CPPs on the mechanism of the uptake and absorption of Ca2+ and bone metabolism. In this study, a monomeric peptide fraction isolated by RP-HPLC (F6-1) that possessed high calcium transport capacity in Caco-2 cell monolayers was separated and characterized. The effects of F6-1 on the absorption mechanisms of Ca2+ in a Caco-2 monolayer model and bone metabolism in rats were investigated. F6-1 was isolated by preparative and analytical RP-HPLC. Results for calcium transport suggested that the rates of Ca2+ transportation by F6-1 were approximately 2.57, 2.87 and 2.38 times higher than those in the control group at 30, 60 and 120 min, respectively. Results of ultraviolet (UV) spectroscopy indicated that the intensity of UV absorption changed because of the binding of Ca2+ to F6-1. Analysis of transepithelial electrical resistance (TEER) and the expression of TRPV6 in Caco-2 cells showed that F6-1 was likely to influence the transcellular pathway of intestinal absorption of Ca2+ rather than the paracellular pathway. Furthermore, the F6-1 group (1% Ca, 0.03% F6-1) exhibited increases in serum Ca2+ levels, femur length and femur Ca and decreases in serum alkaline phosphatase (ALP) levels and urinary pyridinoline content in a Sprague-Dawley rat model, which implied that F6-1 was beneficial for bone calcification. Overall, our results suggested that F6-1 enhanced the transport of Ca2+ in Caco-2 cells by affecting the transcellular pathway by upregulating the expression of TRPV6. F6-1 also improved bone formation and prevented bone resorption to benefit bone health in rats, which provided a basis for using F6-1 in calcium supplements or functional foods.
研究领域:
营养学
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生物化学
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食品科学
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生理学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF FOOD SCIENCE AND TECHNOLOGY
·
2019
·Vol. 54
·期 6
·2123-2131
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IF 2.281
Hui Jia,Lingmin Tian,Bingcheng Zhang,Xin Fan,Dayun Zhao
Summary Previous studies have demonstrated that the undigested or insoluble high molecular fraction of soy protein exerts a lowering effect on serum cholesterol by inhibiting the absorption of cholesterol in the intestinal tract. The aim of this study was to investigate the interaction between the soluble fraction of soy protein peptic hydrolysate and dietary mixed micelles (DMMs) for cholesterol micellar solubility and uptake. The collected soluble tofu peptic hydrolysate (STPH) components, generated from hard and lactone tofu were evaluated by two in vitro models and a Caco-2 cell model after tofu soy protein was digested, thus simulating the gastrointestinal tract. The results showed that the administration of STPH effectively decreased the cholesterol solubility and uptake by 37.6% and 18.99%, respectively, as detected by the in vitro models and the Caco-2 cell model. Current findings demonstrated the potential hypocholesterolaemic benefit of the STPH.
研究领域:
营养学
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生物化学
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DOI
高影响因子
Cell Death & Disease
·
2017
·Vol. 8
·期 7
·e2935
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IF 5.965
Zhou Wei,Yao Jihong,Wang Guangzhi,Chen Zhao,Li Zhenlu,Feng Dongcheng,Li Yang,Qasim Wasim,Tan Wenzhi,Ning Shili,Tian Xiaofeng
Intestinal ischemia–reperfusion (I/R) is a common clinical problem that occurs during various clinical pathological processes. Excessive apoptosis has an indispensable role in intestinal I/R injury. Tumor necrosis factor receptor-associated factor 2 (TRAF2) and PKC ζ have an essential role in apoptosis. Here, we aimed to investigate the effects of PKC ζ and TRAF2 and to explore the correlation between PKC ζ and TRAF2 in intestinal I/R injury. Mice were subjected to intestinal I/R injury in vivo . In vitro experiments were conducted by treating Caco-2 cells with hypoxia/reoxygenation (H/R) stimulation to simulate intestinal I/R. Intestinal tissue samples and Caco-2 cells were examined using various approaches. Intestinal I/R induced the membrane translocation and phosphorylation of PKC ζ . Pretreatment with the PKC ζ activator phosphatidylcholine remarkably attenuated gut injury by suppressing apoptosis. H/R induced PKC ζ to combine with TRAF2, which was phosphorylated by PKC ζ at Ser 55 , but not at Ser 11 , under intestinal I/R or H/R conditions. In addition, TRAF2 Ser 55 phosphorylation increased cell survival by inhibiting cell apoptosis in the H/R model. Mechanistically, TRAF2 Ser 55 phosphorylation promoted NF- κ B activation but suppressed c-Jun activation in Caco-2 cells under H/R conditions. The results of this study demonstrate that the PKC ζ /TRAF2 pathway represents a novel protective mechanism against intestinal I/R injury. Therefore, the PKC ζ /TRAF2 pathway is a novel target for potential treatments of intestinal I/R injury-related diseases.
研究领域:
分子生物学
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细胞生物学
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病理学
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DOI
PubMed
高影响因子
Food & Function
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2020
·Vol. 11
·期 8
·7266-7279
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IF 4.171
Xiaojie Wang,Li Li,Genyi Zhang
Deoxynivalenol (DON) is one of the most widely distributed mycotoxins in the food chain, and the protective effect of kaempferol (KAM) pretreatment against the barrier dysfunction induced by DON in a Caco-2 cell model was investigated using a proteomic approach. The results showed that after KAM pretreatment, both the numbers of down- and up-regulated differentially expressed proteins were significantly lower than those in the DON group. Gene ontology analysis revealed that differentially expressed proteins were enriched in cell adhesion molecule binding, cell junction, and cell junction assembly. Further study demonstrated that KAM pretreatment affected the expression and assembly of tight junction and adherens junction proteins through the PKA pathway and MAPK/ERK pathway to improve the barrier integrity of the Caco-2 cell monolayer, and nutraceutical approach based on bioactive phytochemicals to improve the body's immunity might be an effective strategy to combat the adverse effects of mycotoxins on intestinal barrier function.
研究领域:
毒理学
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药理学
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蛋白质组学
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细胞生物学
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营养学
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DOI
PubMed
高影响因子
Food & Function
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2021
·Vol. 12
·期 12
·5551-5562
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IF 5.396
Mengjie Ma,Han Wang,Yongkai Yuan,Yuanhong Wang,Shuang Yang,Zhihua Lv
The purpose of this study was to investigate the absorption and transport of glycosaminoglycan from Apostichopus japonicus (AHG) and its depolymerized derivatives (DAHG-1, DAHG-2, DAHG-3). The AHG and depolymerized AHGs (DAHGs) were characterized by high-performance gel permeation chromatography (HPGPC), Raman spectroscopy and atomic force microscopy (AFM). The results showed that there was no significant difference of an AHG primary structure and functional groups during the depolymerization. Meanwhile, AFM observation showed that AHG and DAHGs possessed linear structures. In this study, a rapid and sensitive liquid chromatographic post-column derivatization method was used to investigate the absorption of AHG and DAHGs with the Caco-2 cell model, the M cell model and the intestinal recirculating perfusion. It was found that AHG and DAHGs can be absorbed in the intestine, and their transport involved endocytosis.
研究领域:
生物化学
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药学
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营养学
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产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
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2021
·
IF 7.514
Zhuqing Dai,Jiangfeng Song,Ye Chen,Lei Feng,Yayuan Xu,Dajing Li,Caie Wu,Zhongyuan Zhang,Jun Liu
This study aims to develop novel lutein nanoparticles encapsulized by stevioside (LUT-STE, 165 ± 2 nm average particles size) and systematically evaluate its bioavailability. Multiple spectroscopy and NMR analyses showed lutein and stevioside could interact through hydrogen bonds, C H π interaction and van der Waals forces. Molecular docking simulation showed lutein was well distributed in the hydrophobic cavity of stevioside. Analyzed by Caco-2 cellular models, the transported amount of LUT-STE was 2.39 times that of lutein in 120 min with a P app (B → A)/ P app (A → B) value of 0.63 ± 0.04. Nystatin and dynasore significantly reduced the cellular uptake of LUT-STE by 41.3% and 57.7%, respectively. Compared with free lutein, LUT-STE increased the C max in mice plasma by 5.01-fold and promoted the accumulation in multiple organs. LUT-STE promoted the protein expressions of CD36, NPC1L1 and PPARγ in both cell and animal models. In conclusion, stevioside entrapment significantly promote the bioavailability of lutein through multiple transmembrane pathways.
研究领域:
药学
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营养学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2021
·
IF 4.451
Chang Tan,Yanwen Kong,Yuqi Tong,Haotian Deng,Mingyue Wang,Yang Zhao,Meizhi Wan,Sixu Lin,Xiaoxu Liu,Xianjun Meng,Yan Ma
To investigate whether complexes of cyanidin-3-glucoside (C3G) and blueberry pectin (BP) can exert protective effects on lipopolysaccharide (LPS)-induced Caco-2 inflammatory cells, as well as the influence of high hydrostatic pressure (HHP) processing on the activities of the complexes, for determining their anti-apoptosis in vitro . LPS-induced Caco-2 cells were treated with C3G-BP complexes with or without HHP treatment. Results showed that C3G-BP complexes (100–100 µg/mL) inhibited the depolarization of mitochondria and reduced the production of ROS, as demonstrated by the reduced mRNA expression of IL-1β, TNF-α, and IL-8; increased expression of IL-10; and reduced iNOS, COX-2, Bcl-2, and cleaved caspase-3 levels. These findings reveal that C3G-BP exerts anti-apoptosis effects by inhibiting several mediators and cytokines involved in the inflammatory process. Furthermore, HHP-treated C3G-BP complexes better reduced cell apoptosis than untreated complexes, owing to the high pressure-mediated alterations in the monosaccharide composition of the complexes. This study provides insights for the functional changes of anthocynin-pectin complexes during food processing applications.
研究领域:
食品科学
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药理学
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细胞生物学
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炎症研究
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DOI
高影响因子
FOOD CHEMISTRY
·
2026
·
IF 10.4
Luyan Liu,Kaiyue Sun,Xin Xie,Yanghui Chen,Jiahui Wang,Yaxin He,Junjie Yu,Meng Huang,Yan Lin,Juan Chen,Jian Liu,Xian Zhang
Thermal processing promotes advanced glycation end products (AGEs) generation in food. Dietary flavonoids possess anti-oxidative and anti-glycation activities. This study aimed to investigate the effect and underlying mechanism of different pattern diets and flavonoids on AGEs production and AGEs-induced intestinal damage. AGEs production was assessed in chow diet (CD), high-fat diet (HFD), high-fat/high-cholesterol western diet (WD) and flavonoid-supplemented diet during thermal processing and simulated digestion. AGEs-induced intestinal damage and the protective effect of myricetin were evaluated in Caco-2 cells. During thermal processing and simulated digestion, HFD and WD generated more AGEs, N ε -carboxymethyl-lysine and N ε -carboxyethyl-lysine than CD. Flavonoids inhibited AGEs production, with myricetin exhibiting the highest activity. Dietary AGEs impaired intestinal epithelial nutrient transport and barrier function, and promoted intracellular ROS generation through inhibiting Nrf2/Catalase pathway, while myricetin reversed this effect. Altogether, dietary myricetin prevents thermal processing-induced AGEs formation in different pattern diets and mitigates the associated intestinal epithelial damage.
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高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Meng Jiacheng,Qiu Chenxu,Lu Chenyue,He Xin,Zhao Xinghua
To overcome the poor solubility, permeability, and bioavailability of the plant isoflavone daidzein (DAI), a novel salt of DAI with anhydrous piperazine (PIP) was obtained based on cocrystallization strategy. The new salt DAI-PIP was characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier-transform infrared (FT-IR) spectroscopy, and optical microscopy. The results showed that the maximum apparent solubility (Smax) of DAI-PIP increased by 7.27-fold and 1000-fold compared to DAI in pH 6.8 buffer and water, respectively. The peak apparent permeability coefficient (Papp) of DAI-PIP in the Caco-2 cell model was 30.57 ± 1.08 × 10−6 cm/s, which was 34.08% higher than that of DAI. Additionally, compared to DAI, the maximum plasma concentration (Cmax) value of DAI-PIP in beagle dogs was approximately 4.3 times higher, and the area under the concentration-time curve (AUC0-24) was approximately 2.4 times higher. This study provides a new strategy to enhance the dissolution performance and bioavailability of flavonoid drugs, laying a foundation for expanding their clinical applications.
研究领域:
药学
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药物递送
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药理学
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材料科学
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DOI
PubMed
高影响因子
INFLAMMOPHARMACOLOGY
·
2025
·
IF 5.3
Xu Wenxiu,Wang Hongbo,Sun Zhenyu,Zhang Hui,Zhang Zhijun,Sun Xiangrong,Gu Jiayu,Gong Yanling
Limonene, a monoterpene naturally abundant in various Citrus fruits, is widely used as a fragrance component and dietary supplement. Ulcerative colitis (UC), a representative inflammatory bowel disease, is characterized by an arising incidence and considerable impact on human health. Although several reports have demonstrated the beneficial effects of limonene on UC, detailed mechanisms remain incompletely understood. In this study, we employed a dextran sulfate sodium (DSS)-induced UC murine model and a lipopolysaccharide (LPS)-stimulated Caco-2 cell model to explore the mechanisms of limonene on UC. The results revealed that limonene significantly decreased disease activity index (DAI) score and alleviated pathological damage in UC mice, exhibiting therapeutic potential for UC. Limonene significantly inhibited interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and malondialdehyde (MDA) while increased superoxide dismutase (SOD) in both DSS-induced UC mice and LPS-induced Caco-2 cells. Furthermore, limonene significantly increased expressions of Zonula occludens-1 (ZO-1), occludin, and claudin-1, thereby enhancing intestinal barrier integrity. Limonene mitigated UC-associated dysbiosis by shifting the gut microbial composition toward that of healthy controls. Specifically, it modulated the microbiota at the phylum, family, genus and species levels, increasing the abundance of anti-inflammatory bacteria while decreasing inflammatory related taxa. Collectively, our in vivo and in vitro results demonstrate that limonene alleviates UC involving in anti-inflammation, anti-oxidation, restoration of intestinal barrier integrity and regulation of the gut microbiota. Future studies are warranted to explore whether gut microbial metabolites contribute to the protective effects of limonene in UC. Graphical abstract
研究领域:
消化病学
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免疫学
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分子生物学
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药理学
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微生物组学
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氧化应激
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肠道屏障功能
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天然产物药理
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2025
·
IF 6.5
Zi-Lin Li,Guo-Xing Deng,Chuan-Zhou Fang,Yue-Qi Zhao,Jing Yuan,Liang Chen,Hai-Jun Zhong,Feng Guo
Purpose To improve the oral absorption of relugolix (RLGL), which has low oral bioavailability due to its low solubility and being a substrate of P-glycoprotein (P-gp). A solid self-microemulsifying drug delivery system of relugolix (RLGL-S-SMEDDS) was prepared and evaluated in vitro and in vivo.Methods The composition of the solid self-microemulsifying drug delivery system (S-SMEDDS) was selected by solubility study and pseudo-ternary phase diagram, and further optimized by Design-Expert optimization design. The optimized RLGL-S-SMEDDS were evaluated in terms of particle size, zeta potential, morphology analysis, thermodynamic stability, drug release, flow properties, transporter pathways in Caco-2 cells, the influence of excipients on the intestinal transporters, transport within Caco-2 cell monolayers and transport in lymphocyte. In vivo pharmacokinetic study and toxicological study were also conducted.Results The optimum formulation for self-microemulsifying drug delivery system (SMEDDS) consists of Ethyl Oleate (26% of the weight), Solutol HS15 (49% of the weight), Transcutol HP (25% of the weight) and loaded relugolix (4.8 mg/g). The S-SMEDDS was then formed by adsorbing 2.4 g of SMEDDS onto 1 g of hydrophilic-200 silica. In phosphate buffered saline (PBS) (pH 6.8) release medium containing 1% tween 80, the vitro release studies showed 86% cumulative drug release for RLGL-S-SMEDDS and 3.6% cumulative drug release for RLGL suspensions. In vitro cellular uptake experiments revealed that the uptake of RLGL-S-SMEDDS by Caco-2 cells was three times higher than that of free RLGL, and that S-SMEDDS can enhance the drug absorption through lymphatic absorption and inhibition of intestinal transporter. In vivo pharmacokinetic evaluation demonstrated that the oral bioavailability of RLGL-S-SMEDDS was 1.9 times higher than that of RLGL-suspensions. There was no apparent cardiac, hepatic, splenic, pulmonary or renal toxicity on the surface discovered by pathological analysis after oral administration.Conclusion It is evident that S-SMEDDS may be a safe and effective method to improve oral absorption of drugs with low oral bioavailability.
研究领域:
药剂学
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药物代谢动力学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2017
·
IF 3.649
Bingxiang Zhao,Sufang Gu,Yong Du,Minjie Shen,Xiangrui Liu,Youqing Shen
Hydroxysafflor yellow A (HSYA) is the main bioactive flavonoid extracted from the flower of Carthamus tinctorius L ., which is widely used in traditional Chinese medicine for the treatment of myocardial ischemia and cerebral ischemia . HSYA has high water solubility but poor intestinal membrane permeability, resulting in low oral bioavailability. Currently, only HSYA sodium chloride injection has been approved for clinical use and oral formulations are urgently needed. In this study, HSYA solid lipid nanoparticles (SLNs) with the structure of w/o/w were prepared by a warm microemulsion process using approved drug excipients for oral delivery to increase the oral absorption of HSYA. The optimized HSYA SLNs are spherical with an average size of 214 nm and the encapsulation efficiency is 55%. HSYA SLNs exhibited little cytotoxicity in Caco-2 and Hela cells, but increased the oral absorption of HSYA about 3.97-fold in rats, compared to HSYA water solution. In addition, cycloheximide pretreatment significantly decreased the oral absorption of HSYA delivered by SLNs. Importantly, the pharmacodynamics evaluation demonstrated that SLNs further decreased the infarct areas in rats. In conclude, SLNs could be a promising delivery system to enhance the oral absorption and pharmacological activities of HSYA.
研究领域:
药剂学
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药物递送
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中医药学
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药理学
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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）