INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Qiang Chu,Ruoyi Jia,Wen Chen,Yangyang Liu,Yonglu Li,Xiang Ye,Yong Jiang,Xiaodong Zheng
Ethyl Carbamate (EC), as a carcinogen widely found in fermented foods, was verified that its cytotoxicity was associated with oxidative stress. Polysaccharides from natural sources due to their antioxidative capacity have attracted great attention in the past time. In this study, purified polysaccharide from Tetrastigma hemsleyanum vines (TVP) with 64.89 kDA was extracted and conducted multiple analysis to identify its structural information. It could be discovered that TVP was composed of mannose, rhamnose, glucuronic acid, glucose, galactose, and arabinose. In vitro , TVP could inhibit cytotoxicity and genotoxicity, attenuate oxidative damage and mitochondrial dysfunction induced by EC in Caco-2 cells. Meanwhile, TVP could suppress apoptosis by mTOR and Bcl-2 signaling pathways, ameliorate oxidative via Sirt1-FoxO1 and Nrf2-Keap1 signaling pathways. In vivo , EC as well triggered the decline of survival and athletic ability in Caenorhabditis elegans ( C. elegans ) and TVP could reverse the decline. In the meantime, TVP could ameliorate oxidative damage in N2 and daf-2 (-) mutant but fail in daf-16 (-) mutant, which suggested that DAF-16 (FOXO) might affect the antioxidative protection of TVP in C. elegans . In brief, our results manifested that TVP could attenuate EC-induced cytotoxicity both in vitro and in vivo .
研究领域:
药理学
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毒理学
·
分子生物学
·
细胞生物学
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DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2022
·
IF 7.425
Wen-Juan Pan,Lu-Lu Shi,Yu-Ru Ren,Cheng-Ying Yao,Yong-Ming Lu,Yan Chen
Age-associated increase in intestinal permeability is known to relate with gut microbiota dysbiosis and loss of epithelial tissue integrity. To improve healthy aging and prevent age-associated chronic disabilities, the protective potential of polysaccharides from Oudemansiella raphanipes (ORP-1) against age-associated intestinal epithelial barrier dysfunction in d -galactose-induced Caco-2 cells monolayer was investigated. In-vitro results demonstrated that ORP-1 can restore a healthy gut microbial population to handle age-related gut microbiota dysbiosis mainly by facilitating the proliferation and adhesion of probiotics Lactobacillus acidophilus ( L. acidophilus ) and Bifidobacterium bifidum ( B. bifidum ) to compete with intestinal pathogenic Escherichia coli ( E. coli ) for ecological niches and nutrition. Meanwhile, ORP-1 strengthened the intestinal structural integrity primarily by abolishing the aggravation of apoptosis and the age-associated alterations of tight junction (TJ) proteins expression in intestine. These findings highlighted that ORP-1 could be a potential functional food component with preventive utility against age-associated intestinal barrier injury.
研究领域:
胃肠病学
·
药理学
·
营养学
·
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
·
2020
·
IF 5.162
Fenfen Li,Pengcheng Du,Weiyu Yang,Danfei Huang,Shaoping Nie,Mingyong Xie
The intestinal epithelium is known as an important barrier to protect the body from harmful pathogens or toxic substance that may induce intestinal barrier injury. The aim of this study was to investigate the effects of polysaccharide from the seeds of Plantago asiatica L. (PLP) on nonylphenol (NP) induced intestinal barrier injury in vitro . Caco-2 cells were pretreated with PLP, or co-cultured with PLP and NP simultaneously, and cytotoxicity, LDH leakage, transepithelial electrical resistance (TEER), FITC-dextran flux and tight junction (TJ) proteins were conducted to evaluate the intestinal barrier function. The results suggested that PLP pretreatment or co-culture with NP could significantly attenuated NP induced Caco-2 cytotoxicity, suppressed LDH release, restored the TEER value and paracellular permeability of Caco-2 monolayers, which were attributed to enhancing the TJ protein expressions. In addition, PLP co-cultured with NP possessed better protective effects against NP induced cytotoxicity. This study indicated that PLP assuaged NP induced intestinal barrier injury by increasing TJ, and threw light on the development of a dietary supplementation for preventing exogenous toxic substances induced intestinal barrier injury or improving intestinal TJ barrier function.
研究领域:
药理学
·
毒理学
·
细胞生物学
·
胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Science China-Life Sciences
·
2023
·
IF 9.1
Zhang Qian,Ding Haoxuan,Yu Xiaonan,Wang Qiwen,Li Xuejiao,Zhang Ruiqiang,Feng Jie
Iron overload often occurs during blood transfusion and iron supplementation, resulting in the presence of non-transferrin-bound iron (NTBI) in host plasma and damage to multiple organs, but effects on the intestine have rarely been reported. In this study, an iron overload mouse model with plasma NTBI was established by intraperitoneal injection of iron dextran. We found that plasma NTBI damaged intestinal morphology, caused intestinal oxidative stress injury and reactive oxygen species (ROS) accumulation, and induced intestinal epithelial cell apoptosis. In addition, plasma NTBI increased the relative abundance of Ileibacterium and Desulfovibrio in the cecum, while the relative abundance of Faecalibaculum and Romboutsia was reduced. Ileibacterium may be a potential microbial biomarker of plasma NTBI. Based on the function prediction analysis, plasma NTBI led to the weakening of intestinal microbiota function, significantly reducing the function of the extracellular structure. Further investigation into the mechanism of injury showed that iron absorption in the small intestine significantly increased in the iron group. Caco-2 cell monolayers were used as a model of the intestinal epithelium to study the mechanism of iron transport. By adding ferric ammonium citrate (FAC, plasma NTBI in physiological form) to the basolateral side, the apparent permeability coefficient ( Papp ) values from the basolateral to the apical side were greater than 3×10 −6 cm s −1 . Intracellular ferritin level and apical iron concentration significantly increased, and SLC39A8 (ZIP8) and SLC39A14 (ZIP14) were highly expressed in the FAC group. Short hairpin RNA (shRNA) was used to knock down ZIP8 and ZIP14 in Caco-2 cells. Transfection with ZIP14-specific shRNA decreased intracellular ferritin level and inhibited iron uptake. These results revealed that plasma NTBI may cause intestinal injury and intestinal flora dysbiosis due to the uptake of plasma NTBI from the basolateral side into the small intestine, which is probably mediated by ZIP14.
研究领域:
胃肠病学
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微生物学
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
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2020
·
IF 3.701
Yufeng Chen,Guobin Xia,Zhenlei Zhao,Fan Xue,Yanpei Gu,Chun Chen,Ying Zhang
Low bioavailability and stability of 7,8-dihydroxyflavone (7,8-DHF) hinder its potential application in prevention of humans’ disease. 7,8-DHF loaded nanoliposomes decorated by original, crosslinked and glycosylated lactoferrin (LF) were fabricated. The mean particle size of spherical crosslinked and glycosylated LF coating liposomes were larger than uncoated liposomes with a low polydispersity index, and the former had higher encapsulation efficiency (Above 98%). Crosslinked and glycosylated LF coating liposomes had higher antioxidant activity, storage stability, slow-release ability, bioaccessibility and transepithelial transport compared to free 7,8-DHF and 7,8-DHF loaded liposome. Effective hydrogen bonding between phospholipid and 7,8-DHF, while electrostatic interaction and hydrogen bonding between LF proteins and phospholipid existed. The encapsulated 7,8-DHF was in an amorphous state rather than a crystalline form as detected by differential scanning calorimetry. Collectively, crosslinked or glycosylated LF coating liposomes are promising delivery systems for protecting and transporting 7,8-DHF or other relative bioactive components.
研究领域:
药学
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纳米技术
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生物药剂学
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药物递送系统
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产品关联
DOI
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2023
·
IF 8.1
Qiannan Zhao,Jinyi Yang,Jiahui Li,Lei Zhang,Xiaohai Yan,Tianli Yue,Yahong Yuan
Phenolics of mulberry ( Morus alba L.) leaves (MLs) have potential anti-diabetic effects, but they may be chemically modified during gastrointestinal digestion so affect their biological activity. In this study, an in vitro digestion model coupled with Caco-2 monolayer and Caco-2/insulin-resistant HepG2 coculture model were used to study the transport and hypoglycemic effects of phenolics in raw MLs (U-MLs) and solid-fermented MLs (F-MLs). The results of LC-MS/MS analysis showed that the Papp (apparent permeability coefficient, 10 –6 cm/s) of phenolics in digested MLs ranged from 0.002 ± 0.00 (quercetin 3- O -glucoside) to 60.19 ± 0.67 (ferulic acid), indicating higher phenolic acids absorbability and poor flavonoids absorbability. The Papp values of phenolic extracts of F-MLs in Caco-2 monolayer were significantly higher (p > 0.05) than that of U-MLs. Digested phenolic extracts inhibited the activities of sucrase (60.13 ± 2.03%) and maltase (82.35 ± 0.78%) and decreased 9.28 ± 0.84% of glucose uptake in Caco-2 monolayer. Furthermore, a decrease in the mRNA expression of glucose transporters SGLT1 (0.64 ± 0.18), GLUT2 (0.14 ± 0.02) and the sucrase-isomaltase (0.59 ± 0.00) was observed. In Caco-2/insulin-resistant HepG2 co-culture model, phenolic extracts regulated glucose metabolism by up-regulating the mRNA expressions of IRS1 (9.32-fold), Akt (17.07-fold) and GYS2 (1.5-fold), and down-regulating the GSK-3β (0.22-fold), PEPCK (0.49-fold) and FOXO1 (0.10-fold) mRNA levels. Both U-MLs and F-MLs could improve glucose metabolism, and the partial least squares (PLS) analysis showed that luteoforol and p -coumaric acid were the primary phenolics that strongly correlated with the hypoglycemic ability of MLs. Results suggested that phenolics of MLs can be used as dietary supplements to regulate glucose metabolism.
研究领域:
药理学
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营养学
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生物化学
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分子生物学
·
细胞生物学
✓ 已验证
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
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分子生物学
·
心血管科学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2020
·
IF 3.943
Jingqiu He-Yang,Wenting Zhang,Jie Liu,Peng Xue,Xiaoying Zhou
Necrotizing enterocolitis (NEC), a devastating infant disease characterized by severe intestinal necrosis, its pathogenesis is poorly understood, but appears to be multifactorial and highly associated with immaturity of gastrointestinal tract and immature innate-immune system. Breast-milk is effective strategy to protect infants against NEC. This study is using a NEC rat model to investigate the pathological mechanism of NEC involved intestinal-damages, and the therapeutic mechanism of sialylated human milk oligosaccharides (SHMOs) on NEC rats; also using cell model to investigate the effects of SHMOs on colon-epithelial cells (Caco-2) in-vitro . Extraction and characterization of SHMOs from breast milk, establishment of a NEC rat model, histopathological analysis and mast cell accounting of the terminal ileum were taken; The levels of DPPI, TLR4, IL-6, TNF-α, MMP-2/9 and glutathione were measured using various methods. Caco-2 cells were pre-treated with SHMOs and cultured with LPS, histamine, chymase or DPPI, cell viabilities and mitochondrial membrane potential were examined; flow cytometry was used to detect cell cycle. The accumulation of mast cells was found in the ileum of NEC rats, but prohibited by SHMOs treatment; the increased levels of TLR4, DPPI, IL-6, TNF-α, MMP-2/9 in NEC ileum were suppressed by SHMOs in-vivo . SHMOs prevented Caco-2 cells from LPS, histamine, chymase induced damages by surviving cell viability, regulating G0/G1 and S phase in cell cycles, and increasing mitochondrial membrane potential. These findings provide a new insight into the pharmacological mechanism of SHMOs treatment for NEC and suggest that SHMOs needs well attention for therapeutic aims.
研究领域:
儿科
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胃肠病学
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免疫学
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细胞生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2018
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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
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中医药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Sijia Wu,Ping Jiang,Xiaoliang Zhang,Chen Mao,Yaxi Dai,Hong Zhuang,Yong Pang
Understanding the transport mechanism of the peptide Asn-Cys-Trp (NCW) is crucial to improving its intestinal absorption and bioavailability. This study investigated the absorption of NCW through Caco-2 cell monolayers and its interaction with the DPPC bilayers. Results revealed that after a 3 h incubation, the Papp (AP-BL) and Papp (BL-AP) values of NCW at a concentration of 5 mmol/L were (22.24 ± 4.52) × 10–7 and (6.63 ± 2.31) × 10–7 cm/s, respectively, with the transport rates of 1.59 ± 0.32 and 0.62 ± 0.20%, indicating its moderate absorption. NCW was found to be transported via PepT1 and paracellular transport pathways, as evidenced by the significant impact of Gly-Pro and cytochalasin D on the Papp values. Moreover, NCW upregulated ZO-1 mRNA expression. Further investigation of the ZO-1-mediated interaction between NCW and tight junction proteins will contribute to a better understanding of the paracellular transport mechanism of NCW. The interaction between NCW and the DPPC bilayers was predominantly driven by entropy. NCW permeated the bilayers through electrostatic, hydrogen bonding, and hydrophobic interactions, resulting in increased fluidity, flexibility, and disorder as well as phase transition and phase separation of the bilayers.
研究领域:
药理学
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生物物理学
·
细胞生物学
·
膜科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2023
·
IF 6.1
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
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营养学
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药理学
·
微生物学
✓ 已验证
DOI
PubMed
高影响因子
Food & Function
·
2022
·Vol. 13
·期 22
·11676-11689
·
IF 6.317
Abel Wend-Soo Zongo,Daniel Zogona,Mahmoud Youssef,Shuxin Ye,Fuchao Zhan,Jing Li,Bin Li
The intestinal barrier dysfunction associated with chronic inflammation is a major health concern. This work aimed to investigate the protective effect and molecular mechanism of Senegalia macrostachya seed polysaccharide fraction (SMSP2) on inflammation-induced barrier dysfunction using Caco-2 cells and RAW264.7 macrophage co-culture model. The results showed that LPS stimulation of the basolateral RAW264.7 compromised the integrity of the apical differentiated Caco-2 cells monolayer, resulting in decreased transepithelial electrical resistance (TER) and increased inflammatory markers. SMSP2 apical treatment maintained a higher TER value and reduced the epithelial permeability to lucifer yellow (LY) dye. In addition, the SMSP2 group showed a significant decrease in the mRNA level of inflammatory factors such as inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), interleukin (IL)-8, and tumor necrosis factor-α (TNF-α) in the Caco-2 monolayer compared to the LPS group. Moreover, SMSP2 increased the expression of the tight junctions (TJ) zonula occludens (ZO-1), occludin, and claudin-1 at the mRNA and protein levels. Furthermore, the immunofluorescence assay showed that SMSP2 ameliorated the overall distribution of the TJ proteins in the Caco-2 monolayer. SMSP2 application also resulted in the downregulation of the nuclear factor kappa-B (NF-κB) phosphorylation and the myosin light chain kinase (MLCK) expression, which implies that SMSP2 preserved the monolayer integrity from the inflammation-induced barrier disruption through the inhibition of the NF-kB-mediated MLCK signaling pathway activation. Senegalia macrostachya seeds could therefore be a promising functional food that could be used to improve intestinal barrier function.
研究领域:
药理学
·
免疫学
·
细胞生物学
·
分子生物学
·
胃肠病学
✓ 已验证
DOI
PubMed
高影响因子
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