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Two novel peptides derived from oat with inhibitory activity against dipeptidyl peptidase-IV: the related mechanism revealed by molecular docking and in vitro and in situ effects

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Abstract

In recent years, the dipeptidyl peptidase IV (DPP-IV) inhibitors, an antidiabetic drug extending the half-life of incretin, have attracted the researchers’ attention. The current study aimed to explore the inhibitory peptides obtained from oat protein hydrolysates (OPHs) and their derivative peptides against DPP-IV. OPHs obtained by digestion with alcalase, papain, and trypsin exhibited DPP-IV inhibitory activities. Among them, the OPHs produced by digestion with alcalase exhibited the strongest inhibitory effects on DPP-IV (92.92 ± 0.13%). The inhibitory peptides obtained with alcalase digestion were isolated and purified using anion-exchange chromatography (DEAE-52) and volume-exclusion chromatography (Sephadex-G25) sequentially. Liquid chromatography-tandem mass spectrometry was used to identify 11 peptides in total. Molecular docking results showed that the SPVAEVPFLR (SP10, − 8.0 kcal/mol) and LDATDMVALVG (LD11, − 7.1 kcal/mol) had the lowest binding energies with DPP-IV and primarily bound by hydrogen bonds and hydrophobic interactions. Moreover, simulated digestion verified that SP10 and LD11 could resist gastrointestinal degradation. The inhibitory activities of SP10 and LD11 on DPP-IV were investigated in vitro using a monolayer intestinal model of Caco-2 cells. The results indicated that SP10 and LD11 had in situ IC50 values of 167.8 and 269.1 µM, respectively. Therefore, OPHs can be considered promising natural sources of DPP-IV inhibitory peptides.

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Acknowledgements

This work was supported by the Science and Technology Planning Project of Sichuan Province (2022JDRC0039) and Aerospace Science and Technology Collaborative Innovation Center project (BSAUEA5740600223).

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Authors and Affiliations

  1. Department of Food Nutrition and Health, School of Medicine and Health, Harbin Institute of Technology, Mailbox: 1252, No 13, Fayuan Street, Harbin, 150001, Heilongjiang Province, China

    Xinxin Mu, Rongchun Wang, Cuilin Cheng & Ying Ma

  2. Dairy Nutrition and Function, Key Laboratory of Sichuan Province, New Hope Dairy Company Limited, Chengdu, 610023, Sichuan, China

    Qiming Li

  3. Sichuan Engineering Laboratory for High-quality Dairy Product Preparation and Quality Control Technology, Chengdu, 610000, Sichuan, China

    Qiming Li

  4. Zhengzhou Institute, Harbin Institute of Technology, Zhengzhou, 450001, China

    Rongchun Wang

  5. National and Local Joint Engineering Laboratory for Synthesis, Transformation and Separation of Extreme Environmental Nutrients, Harbin Institute of Technology, Harbin, 150001, China

    Rongchun Wang & Cuilin Cheng

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Writing of original manuscripts: Xinxin Mu; Data curation: Xinxin Mu, Ying Ma; Runding access: Rongchun Wang; Monitoring: Rongchun Wang, Cuilin Cheng, Qiming Li; Validation: Ying Ma, Cuilin Cheng; Resources: Qiming Li, Rongchun Wang.

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Mu, X., Wang, R., Cheng, C. et al. Two novel peptides derived from oat with inhibitory activity against dipeptidyl peptidase-IV: the related mechanism revealed by molecular docking and in vitro and in situ effects. Food Measure (2024). https://doi.org/10.1007/s11694-024-02387-z

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