Using Caco-2 cells as novel identification tool for food-derived DPP-IV inhibitors

Caron, Juliette; Domenger, Dorothée; Dhulster, Pascal; Ravallec, Rozenn; Cudennec, Benoît

doi:10.1016/j.foodres.2017.01.002

Cited by 38 publications

(37 citation statements)

References 27 publications

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“…including endopeptidase, aminopeptidase, and dipeptidyl peptidase IV (DPP-IV) (Fan et al, 2018;Sangsawad et al, 2018). Although some literatures has reported that undifferentiated Caco-2 cells can also be used in the study of DPP-IV inhibitory drugs (Caron et al, 2017),…”

Section: Discussionmentioning

confidence: 99%

Assessment of the DPP‐IV inhibitory activity of a novel octapeptide derived from rapeseed using Caco‐2 cell monolayers and molecular docking analysis

Mejı́a

Chen

et al. 2020

J. Food Biochem.

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The Octapeptide ELHQEEPL, which was identified from the rapeseed protein napin showed prominent Dipeptidyl peptidase-IV (DPP-IV) inhibitory activity. The objective of this study was to investigate the DPP-IV inhibitory activity and transepithelial transport of ELHQEEPL in an approaching intestinal condition using Caco-2 cell monolayers. ELHQEEPL and its degraded fragments EL, HQEEP, and methylated ELHQEEPL were transported across Caco-2 cell monolayers through different pathways. Compared with the nonbiological enzyme inhibition test, the in vitro experiment on Caco-2 cell monolayers showed that the IC 50 value of DPP-IV inhibition increased by 43.11% for ELHQEEPL. There was no significant change in DPP-IV gene expression in the Caco-2 cell monolayers upon treatment with ELHQEEPL. Furthermore, molecular docking predicted that the weaker binding between inhibitory peptide and enzyme for the degradation products from ELHQEEPL during transepithelial transport greatly limited its role in inhibiting DPP-IV. Practical applications The DPP-IV inhibitory activity of ELHQEEPL was confirmed using Caco-2 cell monolayers as a novel assessment tool, although its potency was reduced by metabolic degradation. In general, this study reported the use of Caco-2 cell monolayers as a tool for comprehensively studying peptides as sources of DPP-IV inhibitors. A Caco-2 cell-based approach with molecular docking can be adapted for the investigation of intestinal absorption and activity attenuation of food peptides being considered for enzymatic action. Moreover, since the Caco-2 cells express a wide range of enzymes, this method can be used for screening for other active food peptides such as for the

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Section: Discussionmentioning

confidence: 99%

Assessment of the DPP‐IV inhibitory activity of a novel octapeptide derived from rapeseed using Caco‐2 cell monolayers and molecular docking analysis

Mejı́a

Chen

et al. 2020

J. Food Biochem.

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“…In order to screen and identify novel food-derived DPP-IV inhibitors, the exclusive use of biochemical tools represents a major limitation for the lack of several factors that might influence their activity [ 23 ]. Moreover, since in vivo evidence of their potential activity as DPP-IV inhibitors is scarce, the development of an alternative and cost-effective strategy is needed.…”

Section: Discussionmentioning

confidence: 99%

“…A similar cell-based assay has been recently proposed by other authors to evaluate DPP-IV activity in living 7-day-differentiated Caco-2 cells [ 23 ]. Our method is more sensitive and cost-effective, since here undifferentiated 2-day Caco-2 cells are used and a much lower concentration of the substrate Gly-Pro-AMC is employed with respect to the previous method (50 µM versus 1 mM) [ 23 ]. Since the fluorescent substrate concentration and level of enzyme expressed as a function of cell culture age are tightly connected, the optimized conditions here proposed are a good compromise to save time and money.…”

Section: Discussionmentioning

confidence: 99%

Soybean- and Lupin-Derived Peptides Inhibit DPP-IV Activity on In Situ Human Intestinal Caco-2 Cells and Ex Vivo Human Serum

Lammi

Bollati

Ferruzza³

et al. 2018

Nutrients

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Recent investigations have focused on food-derived peptides as novel natural inhibitors of dipeptidyl peptidase IV (DPP-IV), a new target for diabetes. This study aimed to optimize fast, sensitive, and cost-effective DPP-IV assays in situ on human intestinal Caco-2 cells and ex vivo on human serum. Both assays were applied to investigate the inhibitory activity of soy and lupin peptides. The best conditions for in situ DPP-IV activity in Caco-2 cells were obtained using 2-day cells and 50 µM Gly-Pro-AMC. Sitagliptin, used as reference inhibitor, showed a dose-dependent response with a 50% inhibition concentration (IC50) of 0.6 µM. A lower IC50 (0.2 µM) was obtained for sitagliptin on human serum incubated with the substrate for 24 h. Both assays were applied to assess the activity of Lup1 (LTFPGSAED) and Soy1 (IAVPTGVA) on DPP-IV. Lup1 and Soy1 inhibited DPP-IV in situ, with IC50 values of of 207.5 and 223.2 µM, respectively, and maintained their inhibitory activity ex vivo on circulating DPP-IV with a slightly lower potency. These assays can be used to characterize the DPP-IV inhibitory activity of food-derived molecules more accurately than in vitro biochemical tests. This combined approach also considers their effects on the circulating form of DPP-IV, correlated to metabolic diseases.

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“…A methodology utilizing human intestinal epithelial cells, that is, Caco‐2 cells, expressing DPP‐IV has recently been developed by Caron, Domenger, Dhulster, Ravallec, and Cudennec (). The Caco‐2 cell‐based assay has been used to better mimic intestinal physiological conditions including the activity of brush border enzymes and cellular permeability.…”

Section: Assessment Of the Dpp‐iv Inhibitory Properties Of Hydrolysatmentioning

confidence: 99%

Features of dipeptidyl peptidase IV (DPP-IV) inhibitory peptides from dietary proteins

2017

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Dipeptidyl peptidase IV (DPP-IV) is involved in incretin hormone processing and therefore plays a key role in glycemic regulation. This review summarizes the latest developments in food proteinderived DPP-IV inhibitory peptides. The in silico approaches currently used to develop targeted strategies for the enzymatic release of DPP-IV inhibitory peptides from food proteins are outlined.The features within the primary sequences of potent DPP-IV inhibitory di-, tri-, and larger peptides, having half maximal inhibitory activity (IC 50 ) < 100 mM, were evaluated and the outcomes are presented herein. It is proposed that detailed analysis of those food derived peptides identified in humans following ingestion may constitute a practical strategy for the targeted identification of novel bioavailable DPP-IV inhibitory peptides. Human intervention studies are required as the specific role of food protein-derived DPP-IV inhibitory peptides in the regulation of glycaemia in humans remains to be fully elucidated.

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Using Caco-2 cells as novel identification tool for food-derived DPP-IV inhibitors

Cited by 38 publications

References 27 publications

Assessment of the DPP‐IV inhibitory activity of a novel octapeptide derived from rapeseed using Caco‐2 cell monolayers and molecular docking analysis

Assessment of the DPP‐IV inhibitory activity of a novel octapeptide derived from rapeseed using Caco‐2 cell monolayers and molecular docking analysis

Soybean- and Lupin-Derived Peptides Inhibit DPP-IV Activity on In Situ Human Intestinal Caco-2 Cells and Ex Vivo Human Serum

Features of dipeptidyl peptidase IV (DPP-IV) inhibitory peptides from dietary proteins

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