Antioxidants
·
2021
·Vol. 10
·期 6
·930
·
IF 6.313
Nan Zhang,Shunshan Jiao,Pu Jing
Many studies have demonstrated that cabbages possess various biological activities, and our previous studies confirmed that cyanidin-3-diglucoside-5-glucoside (CY3D5G), the major core of red cabbage anthocyanins, exhibited in vitro antioxidant activity. This study further investigated the protective effects of CY3D5G derivative from red cabbage juice (RCJ) on oxidative stress and lifespan in cells andCaenorhabditis elegans, green cabbage juice (GCJ) was used as control. RCJ rather than GCJ significantly improved cell viability and decreased lactate dehydrogenase release in H2O2-induced caco-2 cells. RCJ significantly increased survival during oxidative and heat stress and mean lifespan inC. elegansby 171.63% and 31.64%, and 28.16%, respectively, while GCJ treatment showed no significant effects (p< 0.05). These results might be attributed to significantly (p< 0.05) higher contents of total phenolics, ascorbic acid, glucosinolates, and anthocyanins in RCJ compared to those in GCJ. Additionally, both of them decreased autofluorescence and reproductive capacity, increased body length, but did not alter the intracellular ROS level. Prolonged lifespan by RCJ might require heat-shock transcription factor pathway, sirtuin signaling, and calmodulin kinase II pathway, independent of insulin/insulin-like growth factor-1 signaling pathway. RCJ showed promising antioxidant properties in caco-2 cells andC. elegans, which provided more information on the health benefits of cabbage.Keywords:lifespan;anthocyanins;phytochemicals;HSP-1 pathway;CaMKII pathway;HSP-1 pathway;caco-2 cells
研究领域:
营养学
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生物化学
·
分子生物学
·
老年学
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DOI
PubMed
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 87
·84164-84176
·
IF 3.289
Huipeng Li,Nida El Islem Guissi,Zhigui Su,Qineng Ping,Minjie Sun
Nano-structured lipid carriers (NLCs) have been widely used for oral drug delivery due to their remarkable biocompatibility and biodegradability. In addition to formulation and particle size, particle surface properties are important for overcoming gastrointestinal (GI) barriers to oral drug delivery by lipid-based nanoparticles. In this study, we describe polyethylene glycol (PEG)-based mucus-penetrating NLCs and we report the effect of surface hydrophilic properties on their oral delivery across the GI mucus and intestinal epithelium cells in vivo and in vitro. The solvent evaporation method was used to prepare PEG-modified NLCs (pNLCs) with three different levels of polyethylene glycol (100) monostearate (S100) as the hydrophilic coating material. The stability and cytotoxicity of pNLCs, as well as their uptake by Caco-2 cells and transport across Caco-2 monolayers and mucus-secreting Caco-2/HT29 coculture monolayers, were investigated to confirm the optimal PEG level for oral delivery. In situ single-pass perfusion experiments, in vivo imaging and in vivo oral pharmacokinetic studies were also performed in rodents to evaluate the oral absorption of pNLCs with different hydrophilic surface properties. Our results showed that the hydration layer thickness of the pNLCs increased with the increasing S100 content. NLC containing 20% S100 (pNLC-20%) showed the highest uptake by Caco-2 cells and the most effective permeation through Caco-2/HT29 coculture monolayers compared with unmodified NLC, pNLC-40% and pNLC-80%. In addition, pNLC-20% was the most stable during the process of oral administration and uptake into the blood circulation, as judged by fluorescence resonance energy transfer (FRET). Moreover, in situ single-pass perfusion experiments, ligated intestinal loops tests, in vivo imaging and pharmacokinetics studies also demonstrated that pNLC-20% most rapidly penetrated the intestinal epithelium and had the highest AUC and Cmax of all the NLCs. In conclusion, optimization of surface hydrophilic properties is essential for enhancing the absorption of drugs delivered by oral administration of lipid-based nanocarriers.
研究领域:
药剂学
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纳米技术
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药物递送系统
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DOI
高影响因子
Pharmaceutics
·
2026
·Vol. 18
·期 8
·1010
·
IF 6.9
Zeyu Wen,Xilu Sun,Sumeng Chen,Jinyan Meng,Runlin Yu,Shuyan Guo,Xingyuan Cao
Background: The Biopharmaceutics Classification System (BCS) classifies drug substances according to their aqueous solubility and intestinal permeability; however, its application to veterinary drugs should account for species-specific gastrointestinal physiology. Grapiprant is a selective prostaglandin E2receptor subtype 4 (EP4) antagonist approved as an oral tablet to control pain and inflammation associated with osteoarthritis in dogs, but its properties within the BCS framework remain unclear.Methods: This study evaluated the equilibrium solubility of grapiprant across pH conditions relevant to the canine gastrointestinal tract and calculated the dose number (D0) based on different gastric fluid volumes. A Caco-2 cell monolayer model was used to assess grapiprant intestinal permeability and the effects of time, concentration, pH, and efflux transporter inhibitors on its transepithelial transport.Results: Grapiprant showed relatively small changes in solubility across the tested pH range. D0varied with pH and gastric fluid volume and approached or fell below 1 at larger fluid volumes. In the Caco-2 model, grapiprant showed generally limited apparent absorptive permeability, with permeability varying with pH. Efflux ratios were greater than 1, and verapamil reduced the efflux ratio, suggesting possible P-glycoprotein (P-gp) involvement.Conclusions: These findings suggest that both solubility and apparent intestinal permeability may limit the oral absorption of grapiprant under certain canine-relevant conditions. Accordingly, this study provides a biopharmaceutical characterization of grapiprant within the BCS framework rather than a definitive canine BCS classification, highlighting the importance of considering canine gastrointestinal conditions when interpreting its solubility and permeability. The results may support future optimization of dosing conditions and oral formulations.
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高影响因子
Foods
·
2026
·Vol. 15
·期 4
·704
·
IF 6
Fang Long,Zuomin Hu,Huanzhao Luo,Zhongxing Chu,Shuqin Li,Yaping Zhou,Anping Li,Feijun Luo
Bamboo shoot polysaccharides possess promising bioactivities, but their high molecular weight and complex branched structures limit their functional efficacy. In this study, bamboo (Phyllostachys edulis) shoots were fermented withMonascus purpureusATCC16426 to obtain a novel neutral polysaccharide (FBSP-1). Monosaccharide composition analysis indicated that FBSP-1 comprised glucose (Glc), xylose (Xyl), arabinose (Ara), galactose (Gal), and mannose (Man). Glycosidic linkage and nuclear magnetic resonance (NMR) spectroscopy data revealed that the backbone of FBSP-1 mainly consisted of →2)-α-Manp-(1→, →4)-α-Glcp-(1→, →3)-β-Xylp-(1→, →3)-α-Araf-(1→ and →2)-α-Araf-(1→. Compared with unfermented polysaccharide BSP-1, fermentation markedly altered the monosaccharide profile, increasing Glc, Xyl and Man, decreasing Ara and Gal, and reducing the molecular weight. In H2O2-treated Caco-2 cells, FBSP-1 significantly alleviated oxidative damage by reducing intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels, while enhancing the activities of superoxide dismutase (SOD) and glutathione reductase (GR), demonstrating pronounced antioxidant protective effects. Overall, this study demonstrates thatMonascusfermentation is an effective strategy for the structural remodeling of bamboo shoot polysaccharides, enabling the enhancement of their antioxidant functionality and supporting their potential application as functional ingredients in plant-based antioxidant foods.
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PubMed
高影响因子
FOOD CHEMISTRY
·
2025
·
IF 9.8
Qingchun Zhang,Hao Zhu,Rui Wang,Jianfei He,Christos Ritzoulis,Owen Griffith Jones,Weilin Liu,Wei Tang,Jianhua Liu
Effect of prior hydrolysis and subsequent 36 h glycation on the ability of amyloid-like fibrils derived from β-Lactoglobulin (FG 36 Hβ-Lg) to provide physicochemical stability to fish oil emulsions was systematically determined under varying pH, ionic strength, thermal, and storage conditions. In vitro digestion studies coupled with a Caco-2 cell model investigation evaluated the emulsions' cellular uptake, transmembrane transport, and antioxidant properties. GC–MS analysis of the post-digestion micellar phase revealed that emulsification enhanced the apparent permeability of eicosapentaenoic acid (EPA). FG 36 Hβ-Lg conferred superior EPA transport efficiency and the strongest cellular antioxidant effects on emulsions, compared to proteins modified by hydrolysis or glycation alone, or lacking fibrillar structure. Parallel reaction monitoring showed that FG 36 Hβ-Lg emulsions upregulated key regulatory proteins involved in lipid metabolism and inflammation, such as HMGCR and NFKB1. These findings demonstrate that modified β-Lactoglobulin fibrils improved physical and oxidative stability of emulsions and show promise to enhance bioavailability of omega-3 fatty acids.
研究领域:
食品科学与技术
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营养生物化学
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胶体与界面科学
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分子营养学
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生物物理学
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DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2012
·Vol. 13
·期 3
·836-845
·
IF 1.432
Han Lina,Zhao Yuefang,Yin Lifang,Li Ruiming,Liang Yang,Huang Huan,Pan Shirong,Wu Chuanbin,Feng Min
In the present study, we developed novel insulin-loaded hyaluronic acid (HA) nanoparticles for insulin delivery. The insulin-loaded HA nanoparticles were prepared by reverse-emulsion-freeze-drying method. This method led to a homogenous population of small HA nanoparticles with average size of 182.2 nm and achieved high insulin entrapment efficiencies (approximately 95%). The pH-sensitive HA nanoparticles as an oral delivery carrier showed advantages in protecting insulin against the strongly acidic environment of the stomach, and not destroying the junction integrity of epithelial cells which promise long-term safety for chronic insulin treatment. The results of transport experiments suggested that insulin-loaded HA nanoparticles were transported across Caco-2 cell monolayers mainly via transcellular pathway and their apparent permeability coefficient from apical to basolateral had more than twofold increase compared with insulin solution. The efflux ratio of P
app (B to A) to P
app (A to B) less than 1 demonstrated that HA nanoparticle-mediated transport of insulin across Caco-2 cell monolayers underwent active transport. The results of permeability through the rat small intestine confirmed that HA nanoparticles significantly enhanced insulin transport through the duodenum and ileum. Diabetic rats treated with oral insulin-loaded HA nanoparticles also showed stronger hypoglycemic effects than insulin solution. Therefore, these HA nanoparticles could be a promising candidate for oral insulin delivery.
研究领域:
药剂学
·
生物医学工程
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DOI
PubMed
高影响因子
Polymers
·
2022
·Vol. 14
·期 10
·1975
·
IF 4.967
Wenjun Sun,Yang Tian,Zengming Wang,Hui Zhang,Aiping Zheng
Cyclosporin A nanocrystals (CsA-NCs) interaction with Caco-2 cells were investigated in this study, including cellular uptake and transport across Caco-2 cell monolayers. CsA-NCs of 165 nm, 240 nm and 450 nm were formulated. The dissolution of CsA-NCs was investigated by paddle method. The effect of size, concentration and incubation time on cellular uptake and dissolution kinetics of CsA-NCs in cells were studied. Uptake mechanisms were also evaluated using endocytotic inhibitors and low temperature (4 °C). The cell monolayers were incubated with each diameter CsA-NCs to evaluate the effect of size on the permeation characteristics of CsA across the intestinal mucosa. The results of dissolution study showed that 165 nm CsA-NC had the highest dissolution rate followed by 240 CsA-NC and finally 450 nm CsA-NC. The saturation of cell uptake of CsA-NCs was observed with the increase of incubation concentration and time. 240 nm and 450 nm CsA-NCs had the lowest and highest uptake efficiency at different time and drug concentration, respectively. The uptake of all three-sized CsA-NCs declined significantly in some different degree after the pre-treatment with different endocytosis inhibitors. 165 nm CsA-NC showed a highest transport capacity across monolayers at the same concentration and time. The results suggest that the size of CsA-NCs can not only affect the efficiency of cellular uptake, but also the type of endocytosis. Decreasing particle size of CsA-NCs can improve transport capacity of CsA through cell monolayer.Keywords:cyclosporin A nanocrystals;endocytosis inhibitor;cellular uptake;Caco-2 cell monolayer
研究领域:
药理学
·
生物医学工程
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DOI
PubMed
高影响因子
JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
·
2020
·Vol. 101
·期 8
·3156-3164
·
IF 2.614
Huihui Ke,Tao Bao,Wei Chen
BACKGROUND Rubus chingii Hu is a widely cultivated fruit in China and has declared multiple bioactivities including antioxidative activity. Ethyl carbamate (EC), mostly found in fermented food and alcoholic beverages, is a recognized human carcinogen, and researchers have proposed the correlation between oxidative stress and its toxicity. This study acquired the polysaccharide from R. chingii (RP) and explored its effect on EC-induced cytotoxicity using Caco-2 cells as the cell model. RESULTS Results showed that RP exhibited protection against EC-induced toxicity by repairing redox imbalance as indicative of mitigated mitochondrial membrane potential collapse, attenuated reactive oxygen species overproduction, and impeded glutathione depletion. Moreover, the structural features of RP were characterized and revealed that it was mainly constituted by galacturonic acid and arabinose, with an average molecular weight of 7.039 × 10 5 g mol −1 . CONCLUSION Overall, our results provided a new approach dealing with the toxicity caused by EC from the perspective of oxidative stress and described a new potential healthy value of R. chingii Hu, which could contribute to the development of a promising dietary supplement and functional food. © 2020 Society of Chemical Industry
研究领域:
食品科学
·
毒理学
·
营养学
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DOI
PubMed
高影响因子
Pharmaceutics
·
2023
·Vol. 15
·期 3
·820
·
IF 5.4
Shuangqing Wang,Saige Meng,Xinlei Zhou,Zhonggao Gao,Ming Guan Piao
Drug degradation at low pH and rapid clearance from intestinal absorption sites are the main factors limiting the development of oral macromolecular delivery systems. Based on the pH responsiveness and mucosal adhesion of hyaluronic acid (HA) and poly[2-(dimethylamino)ethyl methacrylate] (PDM), we prepared three HA–PDM nano-delivery systems loaded with insulin (INS) using three different molecular weights (MW) of HA (L, M, H), respectively. The three types of nanoparticles (L/H/M-HA–PDM–INS) had uniform particle sizes and negatively charged surfaces. The optimal drug loadings of the L-HA–PDM–INS, M-HA–PDM–INS, H-HA–PDM–INS were 8.69 ± 0.94%, 9.11 ± 1.03%, and 10.61 ± 1.16% (w/w), respectively. The structural characteristics of HA–PDM–INS were determined using FT-IR, and the effect of the MW of HA on the properties of HA–PDM–INS was investigated. The release of INS from H-HA–PDM–INS was 22.01 ± 3.84% at pH 1.2 and 63.23 ± 4.10% at pH 7.4. The protective ability of HA–PDM–INS with different MW against INS was verified by circular dichroism spectroscopy and protease resistance experiments. H-HA–PDM–INS retained 45.67 ± 5.03% INS at pH 1.2 at 2 h. The biocompatibility of HA–PDM–INS, regardless of the MW of HA, was demonstrated using CCK-8 and live–dead cell staining. Compared with the INS solution, the transport efficiencies of L-HA–PDM–INS, M-HA–PDM–INS, and H-HA–PDM–INS increased 4.16, 3.81, and 3.10 times, respectively. In vivo pharmacodynamic and pharmacokinetic studies were performed in diabetic rats following oral administration. H-HA–PDM–INS exhibited an effective hypoglycemic effect over a long period, with relative bioavailability of 14.62%. In conclusion, these simple, environmentally friendly, pH-responsive, and mucoadhesive nanoparticles have the potential for industrial development. This study provides preliminary data support for oral INS delivery.Keywords:pH responsive;oral insulin delivery;hyaluronic acid;Caco-2 cell;pharmacodynamics
研究领域:
药学
·
生物技术
·
药物递送系统
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2015
·
IF 3.35
Qingxue Fu,Huizhen Wang,Mengxin Xia,Bing Deng,Hongyi Shen,Guang Ji,Guowen Li,Yan Xie
This study investigated the effect of phytic acid (IP6), a potential absorption enhancer of flavonoid components, on tight junction (TJ) integrity in Caco-2 cell monolayers and its possible mechanisms. Transepithelial electrical resistance (TEER) across the monolayers decreased rapidly, and the flux of fluorescein sodium (a paracellular marker) increased after treating with IP6 in a concentration-dependent manner. Confocal microscopy results showed that IP6 produced a concentration-dependent attenuation in the distribution of occludin , ZO-1, and claudin-1. Immunoblot analysis revealed that IP6 could down-regulate the expression level of these TJ proteins , which resulted in the opening of TJ. Additionally, the divalent cations Ca 2 + and Mg 2 + influenced the IP6-induced distribution of occludin, ZO-1, and claudin-1 in different directions, which enhanced barrier function. In conclusion, IP6 can decrease the integrity of Caco-2 cell monolayers by modulating the TJ proteins' localization and down-regulating the expression levels of TJ proteins including claudin-1, occludin, and ZO-1; the reduction effects of divalent cations such as Ca 2 + and Mg 2 + on the regulation of TJ induced by IP6 should be addressed. The present work will offer some useful guidance for the application of IP6 in drug delivery area.
研究领域:
药理学
·
细胞生物学
·
生物物理学
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DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2021
·
IF 6.025
Jinwen Yuan,Siyan Che,Zheng Ruan,Luqing Song,Rongxue Tang,Li Zhang
Polybrominated diphenyl ethers (PBDEs) are persistent organic pollutants (POPs). They are constantly detected in foods . PBDEs can disrupt the intestinal flora , but enterotoxicity is unknown. Luteolin , one kind of flavonoid , has drawn increasing interest as an agent that strengthens the intestinal barrier. This study aimed to evaluate the mitigating effect of luteolin on damage to the intestinal barrier induced by decabromodiphenyl ether (BDE-209) in a Caco-2 cell monolayer model. Results showed that luteolin mitigated BDE-209-induced damage to intestinal epithelial barrier by reducing the levels of reactive oxygen species (ROS), increasing the activity of superoxide dismutase (SOD) and glutathione (GSH), suppressed the secretion of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), and increased the expression of tight junction (TJ) proteins (ZO-1, occludin, and claudin-1). Furthermore, the protective effects were related to the inhibition of extracellular regulated protein kinases (ERK) and nuclear factor kappa-B (NF-κB)/myosin light chain kinase (MLCK) signaling pathways, and the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways. This study is the first to provide strong evidence that BDE-209 can damage the intestinal barrier, and we here investigated the important protective effect of luteolin, which may lay the foundation for the development of luteolin as a dietary supplement to strengthen the intestinal barrier.
研究领域:
毒理学
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药理学
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细胞生物学
·
环境健康
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DOI
PubMed
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2019
·
IF 2.367
Yongshun Sun,Yiping Li,Ying Shen,Jian Wang,Jian Tang,Zhiying Zhao
The aim of this study was to improve the solubility, oral bioavailability, and anti-gastroesophageal reflux activity of curcumin (CM) by preparing two CM-loaded, novel, binary mixed micelles (CM-M). The two CM-M were prepared by ethanol thin-film hydration method. One (CM-T) was prepared using D-alpha-tocopheryl polyethylene glycol 1000 succinate and Solutol®HS15, and the other (CM-F) was prepared using Pluronic®F127 and Solutol®HS15. The entrapment efficiency and drug loading of CM-T were 83.61 ± 0.54% and 2.20 ± 0.65%, respectively, which were lower than those of CM-F (88.66 ± 0.12% and 1.47 ± 0.26%, respectively). TEM results demonstrated that CM-T and CM-F were homogeneous and spherical. The permeability of CM delivered via CM-T and CM-F was enhanced across a Caco-2 cell monolayer, and CM-T and CM-F showed a 5.24- and 4.76-fold increase in relative oral bioavailability, respectively compared with free CM. In addition, the in vivo anti-gastroesophageal reflux study showed that CM-T and CM-F achieved higher anti-gastroesophageal reflux efficacy compared with free CM. Collectively, these findings were indicative of an oral micelle formulation of CM with increased solubility, oral bioavailability, and anti-gastroesophageal reflux activity.
研究领域:
药剂学
·
生物医学工程
·
消化疾病研究
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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）