Anti-inflammatory Effect and Cellular Uptake Mechanism of Peptides from Common Bean (<i>Phaseolus vulga</i> L.) Milk and Yogurts in Caco-2 Mono- and Caco-2/EA.hy926 Co-culture Models

Chen, Yuhuan; Zhang, Hua; Mats, Lili; Liu, Ronghua; Deng, Zeyuan; Mine, Yoshinori; Tsao, Rong

doi:10.1021/acs.jafc.9b03079

Cited by 35 publications

(33 citation statements)

References 42 publications

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“…To define the stimulatory conditions in which endothelial cells express high levels of adhesion and inflammatory markers, EA.hy926 cells, a well-established endothelial model of large vessel endothelium, were treated with 10–200 ng/mL of the prototypic inflammatory cytokine TNF-α [14,15]. To develop an optimal inflammatory cell model with TNF-α-stimulated cells and investigate its response to anti-inflammatory BP, doses (10, 50, and 100 ng/mL) and durations (6 h and 12 h) of TNF-α treatment were optimized.…”

Section: Resultsmentioning

confidence: 99%

Multifunctional Peptides from Spanish Dry-Cured Pork Ham: Endothelial Responses and Molecular Modeling Studies

Martínez-Sánchez

Pérez‐Sánchez

Gabaldón

et al. 2019

IJMS

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Food peptides contain a very wide range of diversified structures, which explains their diverse range of functional activities. Proatherogenic endothelium is related to vasoconstriction, inflammation, and oxidative stress. In this line, four synthetic bioactive peptides from dry-cured pork ham, previously identified according to their Angiotensin I Converting Enzyme (ACE) inhibitory capacity and high bioavailability, were tested. Among them, KPVAAP displayed an estimated IC50 of 59.22 µM for human ACE inhibition, and docking simulations demonstrated the consistency of the noncompetitive binding with the protein. The addition of synthetic peptides to human endothelial cells significantly prevents the expression of genes related to endothelial dysfunction and inflammation (eNOS, ICAM-1, VCAM-1, IL-6) and lowers NF-κB activation (all p < 0.05). In silico dockings showed that the four bioactive peptides interact with the regulatory subunit NEMO of the NF-κB transcription factor at the same site as other characterized inhibitors (CC2-LZ region). This is the first study linking experimental and computational approaches that shows NF-κB to be the target of biopeptides of food origin. These multifunctional peptides from dry-cured pork ham make them good candidates for further research into their therapeutic or preventive use to attenuate the inflammatory atherosclerotic process.

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Section: Resultsmentioning

confidence: 99%

Multifunctional Peptides from Spanish Dry-Cured Pork Ham: Endothelial Responses and Molecular Modeling Studies

Martínez-Sánchez

Pérez‐Sánchez

Gabaldón

et al. 2019

IJMS

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“…All three SPHs inhibited expression of VCAM-1 ( p < 0.05) to a similar extent but did not affect that of ICAM-1 in TNFα-induced EA.hy926 cells. Hydrolysates or peptides with anti-inflammatory effects have been prepared from various food commodities such as meat, zein, beans and egg white, some of which have further been validated their physiological efficacy in animals [ 9 , 29 , 34 , 47 , 65 , 66 ]. Next, we studied the effects of simulated gastrointestinal and transport digestions on the activities of SPH-T, SPH-26L, and SPH-P.…”

Section: Discussionmentioning

confidence: 99%

Spent Hen Protein Hydrolysate with Good Gastrointestinal Stability and Permeability in Caco-2 Cells Shows Antihypertensive Activity in SHR

Fan

Liao

et al. 2020

Foods

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Spent hens are a major byproduct of the egg industry but are rich in muscle proteins that can be enzymatically transformed into bioactive peptides. The present study aimed to develop a spent hen muscle protein hydrolysate (SPH) with antihypertensive activity. Spent hen muscle proteins were hydrolyzed by nine enzymes, either individually or in combination; 18 SPHs were assessed initially for their in vitro angiotensin-converting enzyme (ACE) inhibitory activity, and three SPHs, prepared by Protex 26L (SPH-26L), pepsin (SPH-P), and thermoase (SPH-T), showed promising activity and peptide yield. These three hydrolysates were further assessed for their angiotensin-converting enzyme 2 (ACE2) upregulating, antioxidant, and anti-inflammatory activities; only SPH-T upregulated ACE2 expression, while all three SPHs showed antioxidant and anti-inflammatory activities. During simulated gastrointestinal digestion, ACE2 upregulating, ACE inhibitory and antioxidant activities of SPH-T were not affected, but those of SPH-26L and SPH-P were reduced. ACE inhibitory activity of gastrointestinal-digested SPH-T was not affected after the permeability study in Caco-2 cells, while ACE2 upregulating, antioxidant and anti-inflammatory activities were improved; nine novel peptides with five–eight amino acid residues were identified from the Caco-2 permeate. Among these three hydrolysates, only SPH-T reduced blood pressure significantly when given orally at a daily dose of 1000 mg/kg body weight to spontaneously hypertensive rats. SPH-T can be developed into a promising functional food ingredient against hypertension, contributing to a more sustainable utilization for spent hens while generating extra revenue for the egg industry.

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“…Our recent study has applied the co-culture model of Caco-2/ EA.hy926 to investigate the peptides uptake and involved mechanisms [38]. Although monolayer Caco-2 cells in the co-culture model may mimic the gut-blood-barrier [39], it has some limitations for investigating the transport dynamics of the intestine due to a deficient expression of brush border.…”

Section: Discussionmentioning

confidence: 99%

Red-Osier Dogwood Extracts Prevent Inflammatory Responses in Caco-2 Cells and a Caco-2 BBe1/EA.hy926 Cell Co-Culture Model

et al. 2019

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Red-osier dogwood extracts (RDE) contain high levels of phenolic compounds which have been recognized as natural antioxidants. In this study, the potential of RDE to prevent cardiovascular diseases (CVDs) was evaluated using Caco-2 cells and a co-culture model of Caco-2 BBe1/EA.hy926 cells in Transwell® plates. The results showed that RDE supplementation significantly prevented interleukin-8 (IL-8) production and suppressed the gene expression of IL-8, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and cyclooxygenase 2 (COX-2) in the TNF-α inflamed Caco-2 cells. Meanwhile, the polyphenols (quercetin-3-glucoside, quercetin-glucuronide, rutin, quercetin-3-O-malonylglucoside, and kaempferol-glucoside) in the RDE were validated to be absorbed by Caco-2 BBe1 cells and transported to the basal chamber where EA.hy926 cells were located during 12 h incubation. The transported polyphenols were able to prevent IL-8 production and suppress the gene expression of proinflammatory mediators (TNF-α, ICAM-1, VCAM-1, and COX-2) in the TNF-α or oxidized low-density lipoprotein (ox-LDL) treated EA.hy926 cells. These novel findings demonstrated that phenolic compounds in RDE can be transported to the cardiovascular system by intestinal absorption and mitigate the inflammatory responses of vascular endothelial cells, indicating that RDE could be a natural resource of polyphenols to prevent inflammation cytokine or oxidized lipid-induced CVDs.

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Anti-inflammatory Effect and Cellular Uptake Mechanism of Peptides from Common Bean (Phaseolus vulga L.) Milk and Yogurts in Caco-2 Mono- and Caco-2/EA.hy926 Co-culture Models

Cited by 35 publications

References 42 publications

Multifunctional Peptides from Spanish Dry-Cured Pork Ham: Endothelial Responses and Molecular Modeling Studies

Multifunctional Peptides from Spanish Dry-Cured Pork Ham: Endothelial Responses and Molecular Modeling Studies

Spent Hen Protein Hydrolysate with Good Gastrointestinal Stability and Permeability in Caco-2 Cells Shows Antihypertensive Activity in SHR

Red-Osier Dogwood Extracts Prevent Inflammatory Responses in Caco-2 Cells and a Caco-2 BBe1/EA.hy926 Cell Co-Culture Model

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