Structure-guided discovery of antioxidant peptides bounded to the Keap1 receptor as hunter for potential dietary antioxidants

Yin, Jinwei; Han, Ya-Ning; Liu, Mengqi; Piao, Zan-Hao; Zhang, Xu; Xue, Yuting; Zhang, Yinghua

doi:10.1016/j.foodchem.2021.130999

Cited by 22 publications

(18 citation statements)

References 39 publications

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“…Thus, molecular docking was used to predict the interaction of the major active peptides in RPP with the Keap1 protein. Molecular docking is an important method for computer simulation of the interaction between the protein and ligand, and it has been widely used in high-throughput screening of bioactive substances, such as bioactive peptides . In this study, 10 of the most abundant peptides in RPP were selected for molecular docking with the Keap1 protein, and the Nrf2 protein was used as a control to explore the interaction ability of these peptides with the Keap1 protein.…”

Section: Resultsmentioning

confidence: 99%

“…In addition, they studied the interaction between milk-derived bioactive peptides and Keap1 by the same strategy, which was found to be an antioxidant activity of milk-derived bioactive peptides through the Keap1–Nrf2 signaling pathway . Yin et al found that food-derived tripeptides stably bind to Keap1, block Keap1–Nrf2 interaction, and promote Nrf2 accumulation, thus playing an antioxidant role. Therefore, it was reliable to reveal the antioxidant effects of peptides in DSS-induced acute colitis based on their ability to interact with the Keap1 protein.…”

Section: Resultsmentioning

confidence: 99%

“…The Nrf2 protein was used as a control to predict the binding affinity and molecular interaction of the major peptides in RPP with the Keap1 protein. The tertiary structure of the Keap1 protein was obtained from the Protein Data Bank database (PDB ID: 2FLU, ), and the tertiary structures of peptides were obtained from PEP-FOLD 3 (). Before docking, the protein structures were preprocessed first, including the removal of the water molecule and the original ligand, as well as the addition of hydrogen atoms and electric charges.…”

Section: Methodsmentioning

confidence: 99%

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Rice Protein Peptides Alleviate Dextran Sulfate Sodium-Induced Colitis via the Keap1–Nrf2 Signaling Pathway and Regulating Gut Microbiota

Yang

Huang

Xiong

et al. 2022

J. Agric. Food Chem.

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Inflammatory bowel disease (IBD), with increasing incidence, causes a range of gastrointestinal symptoms and brings distress and impact on the health and lives of patients. The aim of this study was to explore the protective effects of industrially produced rice protein peptides (RPP) on dextran sulfate sodium (DSS)-induced acute colitis in mice and the potential mechanisms. The results showed that RPP treatment alleviated the symptoms of colitis in mice, including weight loss, colon shortening, and injury, decreased the level of disease activity index (DAI), regulated the balance of inflammatory factors and oxidation, activated Kelch-like ECH-associating protein 1 (Keap1)-nuclear factor E2-related factor 2 (Nrf2) signaling pathway, regulated the expression of related antioxidant proteases, and promoted the expression of intestinal tight junction proteins. In addition, RPP maintained intestinal mucosal barrier function and alleviated acute colitis caused by DSS treatment in mice by increasing the value of F/B, increasing the relative abundance of beneficial bacteria such as Akkermansia, and regulating the level of short-chain fatty acids. In conclusion, RPP alleviated colitis symptoms through the Keap1–Nrf2 signaling pathway and regulating gut microbiota, which had the potential as dietary supplements or functional foods.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Rice Protein Peptides Alleviate Dextran Sulfate Sodium-Induced Colitis via the Keap1–Nrf2 Signaling Pathway and Regulating Gut Microbiota

Yang

Huang

Xiong

et al. 2022

J. Agric. Food Chem.

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“…All the peptides synthesized in the present study, except D–4, contained Asp. In addition, aromatic amino acids are considered the main antioxidant amino acids that are a crucial player in antioxidant activity [ 43 , 44 ].…”

Section: Resultsmentioning

confidence: 99%

“…These residues are also reported as key residues for the binding of Keap1 to Nrf2. D–3 also forms three hydrogen bonds with key residues Tyr334, Arg483, and Asn387, which are used to inhibit the binding of Keap1 to Nrf2 [ 33 , 43 , 44 , 55 ]. With Phe577, Tyr572, Ser555, Arg380, Arg415, Tyr525, and Gln530 [ 33 , 43 , 44 , 55 ], D–4 formed a hydrophobic bond.…”

Section: Resultsmentioning

confidence: 99%

Multiple Bioactivities of Peptides from Hydrolyzed Misgurnus anguillicaudatus

Dou¹,

Wu²,

Xia³

et al. 2023

Molecules

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Misgurnus anguillicaudatus (loach) is a widely distributed benthic fish in Asia. In this study, the alkaline protease was used to hydrolyze loach, and the hydrolysate products of different molecular weights were obtained by membrane separation. In vitro antioxidant assays showed that the <3 kDa fraction (SLH-1) exhibited the strongest antioxidant activity (DPPH, hydroxyl radical and superoxide radical scavenging ability, and reducing power), while SLH-1 was purified by gel filtration chromatography, and peptide sequences were identified by LC-MS/MS. A total of six peptides with antioxidant activity were identified, namely SERDPSNIKWGDAGAQ (D-1), TVDGPSGKLWR (D-2), NDHFVKL (D-3), AFRVPTP (D-4), DAGAGIAL (D-5), and VSVVDLTVR (D-6). In vitro angiotensin-converting enzyme (ACE) inhibition assay and pancreatic cholesterol esterase (CE) inhibition assay, peptide D-4 (IC50 95.07 μg/mL, 0.12 mM) and D-2 inhibited ACE, and peptide D-2 (IC50 3.19 mg/mL, 2.62 mM), D-3, and D-6 acted as pancreatic CE inhibitors. The inhibitory mechanisms of these peptides were investigated by molecular docking. The results showed that the peptides acted by binding to the key amino acids of the catalytic domain of enzymes. These results could provide the basis for the nutritional value and promote the type of healthy products from hydrolyzed loach.

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Identification of novel antioxidant collagen peptides for preventing and treating H₂O₂‐induced oxidative stress in HepG2 cells through in vitro and in silico approaches

Du,

Zhang,

Deng

et al. 2023

J Sci Food Agric

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BACKGROUNDNowadays, the prevalence of oxidative stress‐related chronic diseases is increasing. The identification of novel antioxidant collagen peptides to counteract oxidative stress for individuals' health has gained significant attention.RESULTSIn this study, collagen peptides with antioxidant activities were separated and identified by ion chromatography, reversed‐phase high‐performance liquid chromatography and liquid chromatography–tandem mass spectrometry. The identified antioxidant collagen peptides were further screened by molecular docking for Keap1‐targeted peptide inhibitors and their theoretical interaction mechanisms were investigated. Four novel antioxidant collagen peptides, GPAGPIGPVG, GPAGPpGPIG, ISGPpGPpGPA and IDGRPGPIGPA, with high binding affinity to Keap1 were selected. Molecular docking results demonstrated that the putative antioxidant mechanism of the four antioxidant collagen peptides contributed to their blockage of Keap1–Nrf2 interactions. The results of antioxidant activity of the four antioxidant collagen peptides proved that IDGRPGPIGPA exerted a high scavenging capacity for DPPH and ABTS free radicals, while GPAGPpGPIG improved the resistance of cells to hydrogen peroxide‐induced oxidative damage by promoting the activation of intracellular antioxidant enzymes and the production of reduced glutathione in human hepatoma (HepG2) cells.CONCLUSIONThe antioxidant collagen peptides (GPAGPIGPVG, GPAGPpGPIG, ISGPpGPpGPA and IDGRPGPIGPA) will be developed as novel functional food for human health in the near future. © 2023 Society of Chemical Industry.

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Structure-guided discovery of antioxidant peptides bounded to the Keap1 receptor as hunter for potential dietary antioxidants

Cited by 22 publications

References 39 publications

Rice Protein Peptides Alleviate Dextran Sulfate Sodium-Induced Colitis via the Keap1–Nrf2 Signaling Pathway and Regulating Gut Microbiota

Rice Protein Peptides Alleviate Dextran Sulfate Sodium-Induced Colitis via the Keap1–Nrf2 Signaling Pathway and Regulating Gut Microbiota

Multiple Bioactivities of Peptides from Hydrolyzed Misgurnus anguillicaudatus

Identification of novel antioxidant collagen peptides for preventing and treating H₂O₂‐induced oxidative stress in HepG2 cells through in vitro and in silico approaches

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Structure-guided discovery of antioxidant peptides bounded to the Keap1 receptor as hunter for potential dietary antioxidants

Cited by 22 publications

References 39 publications

Rice Protein Peptides Alleviate Dextran Sulfate Sodium-Induced Colitis via the Keap1–Nrf2 Signaling Pathway and Regulating Gut Microbiota

Rice Protein Peptides Alleviate Dextran Sulfate Sodium-Induced Colitis via the Keap1–Nrf2 Signaling Pathway and Regulating Gut Microbiota

Multiple Bioactivities of Peptides from Hydrolyzed Misgurnus anguillicaudatus

Identification of novel antioxidant collagen peptides for preventing and treating H2O2‐induced oxidative stress in HepG2 cells through in vitro and in silico approaches

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Product

Resources

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Identification of novel antioxidant collagen peptides for preventing and treating H₂O₂‐induced oxidative stress in HepG2 cells through in vitro and in silico approaches