Discovery of novel dipeptidyl peptidase-IV inhibitory peptides derived from walnut protein and their bioactivities in vivo and in vitro

The inhibition of dipeptidyl peptidase IV (DPP-IV) has been regarded as a major target for treating type-2 diabetes (T2D). Food-derived peptides are a great source of DPP-IV inhibitory peptides. In this study, we utilized walnut protein as the raw material and hydrolyzed it using four different prot...

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Main Authors: Xinxin Mu, Dan Li, Ran Xiao, Kaifang Guan, Ying Ma, Rongchun Wang, Tianjiao Niu
Format: Article
Language:English
Published: Elsevier 2024-01-01
Series:Current Research in Food Science
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Online Access:http://www.sciencedirect.com/science/article/pii/S2665927124002193
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author Xinxin Mu
Dan Li
Ran Xiao
Kaifang Guan
Ying Ma
Rongchun Wang
Tianjiao Niu
author_facet Xinxin Mu
Dan Li
Ran Xiao
Kaifang Guan
Ying Ma
Rongchun Wang
Tianjiao Niu
author_sort Xinxin Mu
collection DOAJ
description The inhibition of dipeptidyl peptidase IV (DPP-IV) has been regarded as a major target for treating type-2 diabetes (T2D). Food-derived peptides are a great source of DPP-IV inhibitory peptides. In this study, we utilized walnut protein as the raw material and hydrolyzed it using four different proteases. The trypsin hydrolysate exhibited the highest DPP-IV inhibitory activity. A DEAE-52 anion exchange column and a Sephadex G-25 gel filtration column were used to sequentially separate and purify the enzymatic hydrolysates. Mass spectrometry identified 117 peptide sequences, of which LPFA, VPFWA, and WGLP were three highly active DPP-IV inhibitory peptides. Molecular docking results revealed that three peptides primarily bind tightly to DPP-IV through hydrogen bonds and van der Waals forces. The inhibitory activity and absorption transport of the peptides were examined using a Caco-2 cell model. LPFA, VPFWA, and WGLP could cross the Caco-2 cell monolayer intact, with in situ IC50s of 267.9 ± 7.2 μM, 325.0 ± 8.4 μM, and 350.9 ± 8.3 μM, respectively. Oral glucose tolerance tests (OGTT) demonstrated that the three inhibitory peptides significantly improved glucose metabolism in normal ICR mice. This study establishes a theoretical basis for the high-value utilization of walnuts and the therapeutic treatment of T2D.
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spelling doaj-art-82904733e69b488a82065a7141eb4cd82025-08-20T01:59:31ZengElsevierCurrent Research in Food Science2665-92712024-01-01910089310.1016/j.crfs.2024.100893Discovery of novel dipeptidyl peptidase-IV inhibitory peptides derived from walnut protein and their bioactivities in vivo and in vitroXinxin Mu0Dan Li1Ran Xiao2Kaifang Guan3Ying Ma4Rongchun Wang5Tianjiao Niu6Department of Food Nutrition and Health, School of Medicine and Health, Harbin Institute of Technology, Harbin, 150001, ChinaDepartment of Food Nutrition and Health, School of Medicine and Health, Harbin Institute of Technology, Harbin, 150001, ChinaMengniu Hi-Tech Dairy Product Beijing Co., Ltd., Beijing, 101100, ChinaDepartment of Food Nutrition and Health, School of Medicine and Health, Harbin Institute of Technology, Harbin, 150001, ChinaDepartment of Food Nutrition and Health, School of Medicine and Health, Harbin Institute of Technology, Harbin, 150001, ChinaDepartment of Food Nutrition and Health, School of Medicine and Health, Harbin Institute of Technology, Harbin, 150001, China; Corresponding author. Mailbox: 1252, No 13, Fayuan Street, Harbin, 150001, Heilongjiang Province, China.Mengniu Hi-Tech Dairy Product Beijing Co., Ltd., Beijing, 101100, China; Corresponding author.The inhibition of dipeptidyl peptidase IV (DPP-IV) has been regarded as a major target for treating type-2 diabetes (T2D). Food-derived peptides are a great source of DPP-IV inhibitory peptides. In this study, we utilized walnut protein as the raw material and hydrolyzed it using four different proteases. The trypsin hydrolysate exhibited the highest DPP-IV inhibitory activity. A DEAE-52 anion exchange column and a Sephadex G-25 gel filtration column were used to sequentially separate and purify the enzymatic hydrolysates. Mass spectrometry identified 117 peptide sequences, of which LPFA, VPFWA, and WGLP were three highly active DPP-IV inhibitory peptides. Molecular docking results revealed that three peptides primarily bind tightly to DPP-IV through hydrogen bonds and van der Waals forces. The inhibitory activity and absorption transport of the peptides were examined using a Caco-2 cell model. LPFA, VPFWA, and WGLP could cross the Caco-2 cell monolayer intact, with in situ IC50s of 267.9 ± 7.2 μM, 325.0 ± 8.4 μM, and 350.9 ± 8.3 μM, respectively. Oral glucose tolerance tests (OGTT) demonstrated that the three inhibitory peptides significantly improved glucose metabolism in normal ICR mice. This study establishes a theoretical basis for the high-value utilization of walnuts and the therapeutic treatment of T2D.http://www.sciencedirect.com/science/article/pii/S2665927124002193DPP-ⅣPeptidesWalnutOGTTDiabetesMolecular docking
spellingShingle Xinxin Mu
Dan Li
Ran Xiao
Kaifang Guan
Ying Ma
Rongchun Wang
Tianjiao Niu
Discovery of novel dipeptidyl peptidase-IV inhibitory peptides derived from walnut protein and their bioactivities in vivo and in vitro
Current Research in Food Science
DPP-Ⅳ
Peptides
Walnut
OGTT
Diabetes
Molecular docking
title Discovery of novel dipeptidyl peptidase-IV inhibitory peptides derived from walnut protein and their bioactivities in vivo and in vitro
title_full Discovery of novel dipeptidyl peptidase-IV inhibitory peptides derived from walnut protein and their bioactivities in vivo and in vitro
title_fullStr Discovery of novel dipeptidyl peptidase-IV inhibitory peptides derived from walnut protein and their bioactivities in vivo and in vitro
title_full_unstemmed Discovery of novel dipeptidyl peptidase-IV inhibitory peptides derived from walnut protein and their bioactivities in vivo and in vitro
title_short Discovery of novel dipeptidyl peptidase-IV inhibitory peptides derived from walnut protein and their bioactivities in vivo and in vitro
title_sort discovery of novel dipeptidyl peptidase iv inhibitory peptides derived from walnut protein and their bioactivities in vivo and in vitro
topic DPP-Ⅳ
Peptides
Walnut
OGTT
Diabetes
Molecular docking
url http://www.sciencedirect.com/science/article/pii/S2665927124002193
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