JOURNAL OF FOOD SCIENCE
·
2024
·
IF 3.2
Qian Du,Ruiyan Wang,Zeyuan Deng,Jianqun Zhou,Nan Li,Wenwen Li,Liufeng Zheng
Sucrose emerges as a chelating agent to form a stable sucrose-metal-ion chelate that can potentially improve metal-ion absorption. This study aimed to analyze the structure of sucrose-calcium chelate and its potential to promote calcium absorption in both Caco-2 monolayer cells and mice. The characterization results showed that calcium ions mainly chelated with hydroxyl groups in sucrose to produce sucrose-calcium chelate, altering the crystal structure of sucrose (forming polymer particles) and improving its thermal stability. Sucrose-calcium chelate dose dependently increased the amount of calcium uptake, retention, and transport in the Caco-2 monolayer cell model. Compared to CaCl 2 , there was a significant improvement in the proportion of absorbed calcium utilized for transport but not retention (93.13 ± 1.75% vs. 67.67 ± 7.55%). Further treatment of calcium channel inhibitors demonstrated the active transport of sucrose-calcium chelate through Cav1.3. Cellular thermal shift assay and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assays indicated that the ability of sucrose-calcium chelate to promote calcium transport was attributed to its superior ability to bind with PMCA1b, a calcium transporter located on the basement membrane, and stimulate its gene expression compared to CaCl 2 . Pharmacokinetic analysis of mice confirmed the calcium absorption-promoting effect of sucrose-calcium chelate, as evident by the higher serum calcium level (44.12 ± 1.90 mg/L vs. 37.42 ± 1.88 mmol/L) and intestinal PMCA1b gene expression than CaCl 2 . These findings offer a new understanding of how sucrose-calcium chelate enhances intestinal calcium absorption and could be used as an ingredient in functional foods to treat calcium deficiency. Practical Application The development of high-quality calcium supplements is crucial for addressing the various adverse symptoms associated with calcium deficiency. This study aimed to prepare a sucrose-calcium chelate and analyze its structure, as well as its potential to enhance calcium absorption in Caco-2 monolayer cells and mice. The results demonstrated that the sucrose-calcium chelate effectively promoted calcium absorption. Notably, its ability to enhance calcium transport was linked to its strong binding with PMCA1b, a calcium transporter located on the basement membrane, and its capacity to stimulate PMCA1b gene expression. These findings contribute to a deeper understanding of how the sucrose-calcium chelate enhances intestinal calcium absorption and suggest its potential use as an ingredient in functional foods for treating calcium deficiency.
研究领域:
营养学
·
药理学
·
细胞生物学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2023
·
IF 6.1
Nan Li,Ruiyan Wang,Zeyuan Deng,Jianqun Zhou,Wenwen Li,Qian Du,Liufeng Zheng
Sucrose emerges as a metal-ion chelating agent with excellent stability that may increase metal-ion absorption. This study aimed to characterize the structure of zinc–sucrose complex and investigate its ability to promote zinc absorption in Caco-2 monolayer cells and mice. Based on the results of the inductively coupled plasma emission spectrometer (ICP-ES), scanning electron microscopy–energy-dispersive X-ray spectroscopy (SEM-EDX), and Fourier transform infrared spectroscopy (FT-IR), it can be inferred that zinc and sucrose were chelated at a 1:1 ratio, with the hydroxyl groups playing a significant role. The Caco-2 monolayer cell model revealed that zinc–sucrose complex increased the amount of zinc uptake, retention, and transport in a dose- and time-dependent manner. Through the upregulation of genes and proteins for ZIP4, MT1, and DMT1, treatment with zinc–sucrose complex improved the proportion of absorbed zinc utilized for transport compared to ZnCl2 (26.21 ± 4.96 versus 8.50 ± 1.51%). Pharmacokinetic analysis of mice confirmed the zinc absorption-promoting effect of zinc–sucrose complex, as indicated by the considerably higher serum zinc level (4.16 ± 0.53 versus 2.56 ± 0.45 mg/L) and intestinal ZIP4, MT1, and DMT1 gene expression than ZnCl2. Further treatment of different zinc channel inhibitors and CETSA demonstrated the direct interaction of zinc–sucrose complex with ZIP4 protein and ZIP4-mediated cellular transport of zinc–sucrose complex. These findings provide a novel insight into the zinc absorption-promoting mechanism of zinc–sucrose complex, which could be used as an ingredient in functional foods to treat zinc deficiency.
研究领域:
营养学
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药理学
·
分子生物学
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细胞生物学
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生物化学
✓ 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
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细胞生物学
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胃肠病学
✓ 已验证
产品关联
DOI
高影响因子
Pharmacology Research & Perspectives
·
2022
·Vol. 10
·期 1
·e00928
·
IF 2.963
Siyuan Cao,Min Zhang,Minyan Yuan,Dan Yang,Mei Zhao,Shuo Zhang,Pengjiao Wang,Rongping Zhang,Xiuli Gao
The bioavailability of drugs is often related to intestinal metabolism and transport mechanisms. In previous studies, pharmaceutical excipients were recognized as inert substances in clinical safety evaluations. However, a large number of studies have shown that pharmaceutical excipients regulate the metabolism and transport of drugs in the body and improve the bioavailability. The pharmaceutical excipient polyethylene glycol 400 (PEG400) as a good solubilizer and surfactant has the potential to improve the bioavailability of drugs. The combined action of UDP-glucuronosyltransferases (UGTs) and efflux transport proteins is responsible for the intestinal disposition and poor bioavailability of baicalein. Our aim is to study the effect of PEG400 on the absorption of baicalein on the Caco-2 monolayer, and confirm the interaction of PEG400 with UGTs (UGT1A8 and UGT1A9) and efflux transports. We initially found that baicalein in the Caco-2 monolayer would be metabolized into glucuronide conjugates BG and B6G under the action of UGT1A8 and UGT1A9 on the endoplasmic reticulum membrane, and then mainly excreted to different sides by acting of MRP and BCRP. The addition of PEG400 significantly accelerated the metabolism of B in Caco-2 cells and increased the penetration of BG and B6G. Furthermore, PEG400 also significantly decreased the efflux ratio of BG and B6G, which was the evidence of the interaction with the efflux transporters. In the in vitro intestinal microsome regeneration system, low concentration PEG400 decreased the K m value of UGT1A8 and UGT1A9 (key enzymes that mediate the production of BG and B6G); high concentration PEG400 enhanced the V max value of UGT1A8 and UGT1A9. In conclusion, our results determined that PEG400 interacted with some UGTs and efflux transporters, which were the main factors affecting the absorption of baicalein.
研究领域:
药学
·
药理学
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药物代谢
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PROCESS BIOCHEMISTRY
·
2020
·
IF 2.952
Kai Lin,Zhao Ma,Mythili Ramachandran,Cristabelle De Souza,Xue Han,Lan-wei Zhang
The purpose of this study was to explore the effects of KYIPIQ, an angiotensin I-converting enzyme (ACE) inhibitory peptide found in yak milk casein, on the production of nitric oxide (NO) in human vascular endothelial cells (HUVECs). Additionally, we also sought to study the transport pathway of this peptide across monolayers of the human epithelial colorectal adenocarcinoma cell line (Caco-2). Treatment with peptide KYIPIQ increased NO synthesis and expression of phosphorylated endothelial nitric oxide synthase (eNOS) in HUVECs. Our results demonstrate that KYIPIQ-induced eNOS phosphorylation is dependent on the protein kinase B (Akt) activation pathway. Furthermore, our data indicate that the peptide KYIPIQ can be transported across the Caco-2 cell monolayer and that paracellular transport is the main transcellular mechanism. Thus, our studies suggest that KYIPIQ can be potentially used as a therapeutic agent for the treatment of hypertension.
研究领域:
药理学
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细胞生物学
·
分子生物学
·
心血管科学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2018
·
IF 3.115
Min Zhang,Ying Peng,Mengyue Wang,Beibei Gao,Lijuan Zhao,Xiaobo Li
Ethnopharmacological relevance In traditional Chinese medicine , processed aconite root (lateral root of Aconitum carmichaelii Debx.) is used as the principle herb of the Si-Ni decoction (SND) formula due to its cardiotonic effect, while its cardiotoxicity and neurotoxicity caused by diester and monoester diterpenoid alkaloids are reduced by compatibility of dried ginger and honey-processed liquorice in SND. Aim of the study To investigate the detoxification of processed aconite root by compatibility of SND from the perspective of intestinal absorption with metabolism in intestinal bacteria . Materials and methods Decoctions of processed aconite root (AD), processed aconite root and honey-processed liquorice (ALD), and SND with the same amount of each herb were prepared, then were incubated in human intestinal bacteria juice (IBJ) in vitro for different durations. Bidirectional transmembrane transports of these decoctions and their IBJ-incubated decoctions were conducted on Caco-2 monolayers. Correlation between efflux ratios changes of benzoylmesaconine, benzoylaconine, benzoylhypaconine (monoester-diterpenoid alkaloids, MDAs) and hypaconitine (diester-diterpenoid alkaloids) from processed aconite root, and metabolic trends of compounds from honey-processed liquorice and dried ginger were also performed. Results The absorption of MDAs from processed aconite root was increased by combination with honey-processed liquorice in ALD, but they were decreased significantly by the addition of dried ginger in SND. Take benzoylhypaconine for example, the P app, AP to BL soared from ( 3.13 ± 0.18) × 10 −7 cm/s in AD to (23.32 ± 3.51) × 10 −7 cm/s in ALD, while it dropped to (1.12 ± 0.17) × 10 −7 cm/s in SND. When herb combined decoctions metabolised by intestinal bacteria for 12 h, the efflux ratio of benzoylhypaconine were both increased from 0.56 to 1.21 in ALD and from 1.10 to 2.61 in SND, which was correlative with the generation of davidigenin and glycyrrhetic acid (the metabolites of chalcones and pentacyclic triterpenoids from liquorice) in ALD and with the metabolism of [6]-gingerol (the major compound from dried ginger) in SND, respectively. Conclusions Compatibility of SND altered the intestinal absorption of toxic MDAs and hypaconitine from processed aconite root. In SND, dried ginger rather than honey-processed liquorice played the role of detoxification of these toxic compounds in the intestinal absorption. The intestinal detoxification of SND was significantly and strongly correlative with metabolism of dried ginger and honey-processed liquorice by intestinal bacteria, simultaneously.
研究领域:
药理学
·
民族药理学
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微生物学
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毒理学
·
中医药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2020
·
IF 8.758
Yuhao Zhou,Liang Liu,Yue Cao,Shuangjiang Yu,Chaoliang He,Xuesi Chen
Oral insulin delivery has revolutionized diabetes treatment, but challenges including degradation in the gastrointestinal environment and low permeation across the intestinal epithelium remain. Herein, to overcome these barriers, we developed a novel biodegradable nanocomposite microsphere embedded with metal–organic framework (MOF) nanoparticles. An iron-based MOF nanoparticle (NP) (MIL-100) was first synthesized as a carrier with an insulin loading capacity of 35%. The insulin-loaded MIL-100 nanoparticles modified with sodium dodecyl sulfate (Ins@MIL100/SDS) promoted insulin permeation across Caco-2 monolayer models in vitro. To improve resistance to the gastric acid environment, Ins@MIL100/SDS nanoparticles were embedded into a biodegradable microsphere to construct the nanocomposite delivery system (Ins@MIL100/SDS@MS). The microspheres effectively protected the MOF NPs from rapid degradation under acidic conditions and could release insulin-loaded MOF NPs in the simulated intestinal fluid. After the oral administration of Ins@MIL100/SDS@MS into BALB/c nude mice, increased intestinal absorption of the insulin was detected compared to the oral administration of free insulin or Ins@MIL100/SDS. Furthermore, significantly enhanced plasma insulin levels were obtained for over 6 h after oral administration of Ins@MIL100/SDS@MS into diabetic rats, leading to a remarkably enhanced effect in lowering blood glucose level with a relative pharmacological availability of 7.8%. Thus, the MOF-nanoparticle-incorporated microsphere may provide a new strategy for effective oral protein delivery.
研究领域:
药学
·
纳米技术
·
药物递送系统
·
糖尿病治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2025
·
IF 4
Huilin Deng,Yaozhong Zheng,Qiongyao Wang,Jiaqi Peng,Weibin Bai,Lingmin Tian,Zouyan He,Rui Jiao
Mangiferin (MGF), a C-glycosyl xanthone from the mango plant, offers various health benefits but has low absorption, mostly remaining in the gut where it interacts with microbes. This study examines MGF's effects on human gut microbiota and metabolite profiles after in vitro digestion and fermentation with feces. Findings indicate MGF had limited permeability (under 2 %) across the Caco-2 monolayer, with most being fermented by microbes. MGF utilization increased post-digestion and fermentation, significantly altering gut metabolite profiles by boosting lipid and benzenoid abundance while reducing organic acids. It also promoted beneficial bacteria like Bacteroides and Bifidobacterium , decreasing harmful genera such as Sutterella . Metabolomic analysis revealed enhanced pathways for unsaturated fatty acid synthesis and longevity, primarily through oleic and linolenic acids, highlighting MGF's role in modulating gut health.
研究领域:
胃肠科学
·
微生物学
·
营养生物化学
·
代谢组学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2023
·
IF 6.1
Junjie Tan,Qingyu Ma,Jiao Li,Qiuming Liu,Yongliang Zhuang
The bioavailability of rambutan peel polyphenols (RPPs) was studied via in vitro simulated digestion, a Caco-2 monolayer cell model, and colonic fermentation. Total phenolic content of RPPs decreased with the progress of the simulated digestion. A total of 38 phenolic compounds were identified during the digestion and colonic fermentation, of which 12 new metabolites were found during colonic fermentation. The possible biotransformation pathways were inferred. Geraniin was transformed into corilagin, ellagic acid, and gallic acid during the digestion and colonic fermentation. Ellagic acid could be further transformed into urolithin under the action of intestinal microbiota. The transformation of ellagitannins could be beneficial to transport on Caco-2 monolayer cell. The antioxidant capacity of RPPs increased with the progress of gastrointestinal digestion. Furthermore, RPPs could increase the yield of short-chain fatty acids, decrease the pH value, promote the growth of beneficial bacteria, and inhibit the growth of pathogenic Escherichia coli/Shigella during colonic fermentation.
研究领域:
食品科学
·
营养学
·
药理学
·
微生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2023
·
IF 6.1
Zhengming Xu,Shuang Liu,Huining Lai,Lijun You,Zhengang Zhao
Arbutin, salidroside, polydatin, and phlorizin are typically natural bioactive phenolic glycosides. To improve the liposolubility and bioavailability, highly liposoluble derivatives including 6′-O-lauryl arbutin, 6′-O-lauryl salidroside, 6″-O-lauryl polydatin, and 6″-O-lauryl phlorizin were efficiently synthesized by enzymatic acylation in a green solvent 2-MeTHF. Their reaction conversions reached 84.4, 99.5, 99.8, and 89.1%, respectively, when catalyzed by Lipozyme 435 at 20 mg/mL at 50 °C. As expected, the derivatives had high log P (1.66–2.37) and retained good antioxidant activity, making them potential alternatives to butylated hydroxytoluene (BHT) and tert-butyl-hydroquinone (TBHQ) in lipid systems. Then, the intestinal permeability characteristics and metabolism of phenolic glycosides and their derivatives were investigated based on Caco-2 monolayers. The permeability of polydatin and phlorizin was mainly through active transport, but that of arbutin and salidroside involved both passive diffusion and active uptake. The acylated derivatives suffered from severe CES-mediated hydrolysis but exhibited a larger transported amount than phenolic glycosides.
研究领域:
药学
·
有机化学
·
生物化学
·
药理学
✓ 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）