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peptidomics
Food Bioscience · 2025 · IF 5.9

Identification and molecular mechanism of novel antioxidant peptides from fermented pork trimmings: Integrated peptidomics, molecular docking/dynamics, and cell experiments

Zeyuan Liu,Chao Zhang,Lifang Zou,Xingguang Chen,Baocai Xu

Pork trimmings, a major and underutilized by-product of pork processing, possess considerable potential for further exploitation. In this study, antioxidant peptides were isolated and identified from fermented pork trimmings, and their protective mechanisms against ethanol-induced oxidative damage in HepG2 cells were investigated. Utilizing a strategy integrating peptidomic analysis with molecular dynamics simulations, four novel peptides—VGWGR, LPPPR, LGPRYR, and WGGR—were identified, and their specific molecular interactions with Keap1 were elucidated. Among these, VGWGR exhibited the strongest binding affinity to Keap1, outstanding free radical scavenging capacity in vitro , and significant cytoprotective effects. Mechanistic studies further revealed that VGWGR activates the Keap1/Nrf2 pathway, leading to substantial upregulation of downstream antioxidant proteins (HO-1 and NQO1) and increased activities of endogenous antioxidant enzymes. This study not only enhances the value-added utilization of pork trimmings but also supports the potential of VGWGR as a functional food ingredient.

CAS / MDL: 1898-66-4 28752-68-3
研究领域: 食品科学与技术 · 分子生物学 · 生物信息学 · 营养生物化学 · 肽类研究
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2026 ·Vol. 27 ·期 5 ·2364 · IF 5.6

Artificial Neural Network-Guided Discovery of Antioxidant Peptides from Peony (Paeonia ostii) Seed Meal: Peptidomics, Molecular Mechanism, and Cellular Validation

Tianrong Zhang,Xin Wang,Peng Ye,Yuhan Liu,Ming Zhao,Ziyan Liu,Yuan Zhao,Jinling Fan,Bin Zhang

Peony seed meal (PSM), a protein-rich by-product of oil extraction from Paeonia ostii , represents an underutilized resource with significant potential for functional ingredient development. In this study, an integrated strategy combining artificial neural network (ANN)-guided hydrolysis, peptidomics, molecular simulation, and cellular validation was employed to identify antioxidant peptides from PSM. Neutrase was selected as the optimal protease, and hydrolysis conditions were optimized using a backpropagation ANN model (R = 0.9935), yielding a hydrolysate with strong radical-scavenging activity (DPPH • IC 50 = 0.30 mg/mL; ABTS •+ IC 50 = 0.07 mg/mL). LC–MS/MS identified 364 peptides, predominantly low-molecular-weight sequences. In silico screening highlighted four candidates (FRF, WQFR, FEFR, and RWL) with favorable binding toward ABTS •+ , DPPH • , and Keap1. Molecular docking and 100 ns molecular dynamics simulations confirmed stable peptide–Keap1 interactions, particularly for FRF. Cellular assays demonstrated that FRF and RWL significantly protected HepG2 cells against H 2 O 2 -induced oxidative damage by restoring antioxidant enzyme activities (SOD, CAT, and GSH-Px). Collectively, this study establishes a systematic workflow for discovering plant-derived antioxidant peptides and supports the sustainable valorization of PSM as a functional food ingredient.

CAS / MDL: 9001-73-4
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2026 ·Vol. 74 ·期 33 ·26401-26416 · IF 6.7

Explainable Deep Learning Models Coupled with Peptidomics for Screening Antibacterial Peptides from In Vitro Simulated Digestion Hydrolyzates of Jinhua Ham Broth

Yang Ziyi,Zhang Feng,Cui Zhiyong,Zhang Wangang

An explainable deep learning ensemble model integrated with peptidomics was developed to discover antibacterial peptides generated during simulated gastrointestinal digestion of Jinhua ham broth. Simulated digestion increased small peptides and free amino acids, and the resulting peptides inhibited Escherichia coli , Staphylococcus aureus , Salmonella typhimurium , and Listeria monocytogenes by disrupting cell walls and membranes. Peptidomic analysis identified 1,325, 1,694, and 1,980 peptide sequences in undigested, gastric, and intestinal digests, respectively. A KOA-optimized CNN-BiLSTM-att-RF ensemble was trained on antimicrobial peptide datasets with 1,000–15,000 training entries, and SHapley Additive exPlanations were used to perform explainability analysis of the model. The model trained on 1,3000 entries achieved the best overall performance and was applied to screen intestinal peptides. The ten top-ranked peptides were synthesized, and eight showed minimum inhibitory concentrations (MICs) lower than or not significantly different from that of nisin Z, and the most potent peptide, Pep-1, exhibited an MIC of 7.5 μM.

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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2025 · IF 6.2

Screening Myocardial Protective Peptides from Bovine Myocardium Hydrolysates: A Peptidomics-Activity Guided Strategy Integrating Fractionated Extraction, Multivariate Analysis, and Random Forest

Minzhi Zhou,Wen Li,Lin Zheng,Mouming Zhao

This study aimed to investigate the protective effects of bovine myocardium hydrolysates prepared from different protein fractions on H2O2-induced myocardial injury in H9c2 cells and to develop an effective way to explore potential myocardial protective peptides. Results showed that, as compared with bovine heart and its water-soluble protein fraction, myocardium hydrolysate prepared from salt-soluble protein fraction demonstrated better myocardial protective activity, significantly increasing cell viability and activities of antioxidant enzymes (SOD and CAT), while reducing contents of myocardial injury markers (LDH, CK-MB, and cTnT). Ten novel myocardial protective peptides (FR, LK, LPF, RVL, SLL, FDIF, FQPS, GLPPILN, SEAPPHIF, and TEAPLNPK) were identified following a peptidomics-activity guided strategy integrating multivariate analysis and a random forest model. Molecular docking analysis revealed potential molecular mechanisms that might act on myocardial injury-related targets such as AKT1, STAT3, and MMP9. This study may provide insights for the rapid identification of food-derived myocardial protective peptides.

CAS / MDL: 7722-84-1
研究领域: 食品科学 · 肽组学 · 分子生物学 · 心血管药理学 · 营养生物化学
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ANALYTICAL AND BIOANALYTICAL CHEMISTRY · 2024 · IF 3.8

Long-term dysregulation of plasma peptidome in mild and multiple COVID-19 recovered patients revealed by a novel efficient peptidomics workflow

Song Zhijing,Liu Chaoran,Liu Yaozhou,Bian Zheng,Sun Qing,He Ting,Su Rong,Huang Shengchun,Dai Ningbin,Zhao Ke li,Li Yan,Liang Kai

After recovering from COVID-19, many patients experience “long COVID” symptoms. Existing research has predominantly focused on moderate to severe cases, with limited studies examining mild cases and recurrent infections. The circulating low-molecular-weight (LMW) peptidome, involving lipid metabolism, coagulation, and immune pathways, is crucial for understanding COVID-19’s long-term effects. We developed a peptidomics workflow utilizing solid-phase extraction with highly wrinkled GO-Fe 3 O 4 composite materials (HWGO-F) and nanoLC-MS/MS detection. By altering the pH, HWGO-F enhances plasma peptide adsorption and purification. Compared to traditional methods, our workflow offers improved detection depth and reproducibility for over 70% of peptide signals with CV < 20%. We investigated plasma peptide profiles in mild COVID-19 patients post-recovery from single or second infections. The findings indicate persistent abnormalities in initial COVID-19 infections’ plasma peptide profiles, gradually diminishing over time. Secondary infections prolong recovery. Disrupted functions include lipid metabolism, coagulation and complement cascades, and infection-related pathways. Lipid metabolism may normalize within 3 months, while coagulation and immune abnormalities can last 3–6 months. After secondary infections, lipid metabolism irregularities may last at least 1 month, with extended coagulation and immune imbalances. These results provide a theoretical foundation for understanding the widespread occurrence of long COVID and guide recovery care for mild cases. Graphical

CAS / MDL: 1317-61-9
研究领域: 医学 · 生物化学 · 流行病学
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FOOD CHEMISTRY · 2025 · IF 9.8

A peptidomics-based investigation of the synergistic effects of neutral and Alcalase proteases on release of antioxidant peptides from soybean protein isolates

Shulong Cai,Liqi Fan,Dan Liu,Changxing Wei,Na Yang,Xichao Fu,Rong Tang,Jucai Xu,Sheng Yin,Xin Chen

Alcalase and neutral protease are widely employed for producing soybean antioxidant peptides, but their synergy mechanisms remain unclear. In this work, soybean protein isolate (SPI) was hydrolyzed synergistically by the two proteases. The products by Alcalase exhibited a larger proportion of low molecular-weight (MW, <1 kDa) peptides compared to those from neutral protease (87.74 % vs 76.08 %). After synergistic hydrolysis, an “averaging” effect on free amino acid composition and MW distribution was observed, but the peptide length distribution shifted evidently towards dipeptides (57.07 % with simultaneous enzyme use, compared to 20.43 % and 33.70 % for individual enzymes). Similarly, the N/C-terminal residue distribution also displayed an ‘averaging’ trend. Furthermore, synergistic processing increased the proportion (approximately 7 %) of potential antioxidant peptides with predicted probability >0.7, aligning with observed non-additive antioxidant activities and suggesting a synergistic mechanism beyond simple additivity. We hope the work could provide guidance and references for the target peptide release from SPI.

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Food Bioscience · 2026 · IF 5.9

Unraveling novel pancreatic lipase and cholesterol esterase inhibitory peptides in Oryza Sativa L. and their mechanism by peptidomics, molecular dynamics simulations, and cell study

Liuyi Wei,Taoying Wu,Hao Wu,Li Wen,Bo Cui,Yunhui Cheng

Rice-derived peptides are a sustainable protein source with emerging lipid regulation functions. In this study, peptides with novel pancreatic lipase (PL) and cholesterol esterase (CE) inhibition from rice protein hydrolysates (RPHs) were identified by peptidomics. Then their alleviating effects and mechanisms on lipid accumulation in cells were investigated. 55 peptides were identified, showing significant enrichment of Phe, Pro, Arg, and Leu, with hydrophobic/polar amino acids at terminal positions. Among them, five peptides (WQ7, FR6, GF6, GA7, and GY7) exhibited potent inhibitory activity against PL and CE, with IC 50 values of 0.19-0.70 μg/mL and 0.22-0.25 μg/mL, respectively. Molecular docking studies revealed that five peptides bind stably to the active sites of PL (Phe77, Tyr114, Phe215, and His263) and CE (Ser194 and His435) through hydrogen bonding, PI-alkyl, and PI-PI interactions. Dynamic simulations demonstrated that three peptides (WQ7, FR6, and GF6) form stable complexes with both CE and PL, exhibiting strong binding affinity. In vitro study confirmed that these peptides reduced levels of TC, TG, and LDL-c while increasing HDL-c content, with WQ7 showing superior efficacy. Western blot and qPCR results indicated WQ7 regulated lipid metabolism by suppressing the PPARγ pathway and downregulating the protein expression of related factors, such as ACS, FASN, and SREBP-1c. This study showed that the WQ7, a multifunctional bioactive peptide, demonstrates direct enzyme-inhibitory activity and regulates core transcriptional pathways, providing theoretical support for utilizing rice protein in the development of lipid-lowering functional food.

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LWT-FOOD SCIENCE AND TECHNOLOGY · 2023 · IF 6

Identification and molecular mechanism of novel tyrosinase inhibitory peptides from the hydrolysate of 'Fengdan' peony (Paeonia ostii) seed meal proteins: Peptidomics and in silico analysis

Yuan Zhao,Tianrong Zhang,Yuzhe Ning,Di Wang,Fan Li,Yupu Fan,Jiyun Yao,Guoyan Ren,Bin Zhang

Natural and potent tyrosinase inhibitors are in high demand in the food , cosmetic, and pharmaceutical industries. In this study, the hydrolysate was prepared from the peony ( Paeonia ostii ) seed meal proteins (PSMP) by Neutrase with high tyrosinase inhibitory activity. The peptide profile analysis exhibited that there were 594 peptides from 28 proteins, among which 39 peptides were predicted to have high bioactivity, good solubility, and non-toxicity, and were suitable for oral or topical administration by in silico analysis. Molecular docking demonstrated that 38 of the 39 peptides can be promising tyrosinase inhibitors as they had lower or the same binding energies as the tyrosinase inhibitor kojic acid. The interaction mechanism analysis for the top 3 potent peptides demonstrated that 5 out of 8 catalytic residues were involved in each interaction, in which hydrogen bonding was crucial for the peptide SFAPRFD, and both hydrogen bonding and hydrophobic interaction were important for peptides HYGR and SPGRLP. As demonstrated by in vitro test, these three peptides were potent tyrosinase inhibitors with IC 50 ranging from 0.95 to 1.58 mmol/L. Our findings highlight that PSMP can be a valuable source of natural tyrosinase inhibitory peptides for various industrial applications.

CAS / MDL: 9001-73-4
研究领域: 食品科学 · 化妆品科学 · 药理学
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Food Bioscience · 2026 · IF 6.2

Identification and molecular mechanisms of DPP-IV inhibitory peptides from fish maw collagen hydrolysates: An integrated approach combining targeted enzymatic hydrolysis, peptidomics, molecular dynamics, and network pharmacology

Gang Han,Yuhao Zhang,Xu Zhao,Chun Cui

Collagen-rich aquatic materials are promising sources of food-derived bioactive peptides, yet the DPP-IV inhibitory potential of fish maw collagen remains insufficiently explored. In this study, fish maw collagen was hydrolyzed to prepare DPP-IV inhibitory peptides, and their peptide basis and potential inhibitory mechanisms were investigated. Among five commercial proteases, Novozymes 37071 was selected for its superior hydrolytic efficiency and DPP-IV inhibitory activity. A practical hydrolysis condition of 55 °C, 6 h, 2.0% enzyme dosage, and pH 9.0 was selected and verified, yielding a hydrolysate with 97.03% protein recovery, 20.68% degree of hydrolysis, and 66.62% DPP-IV inhibition. The optimized hydrolysate showed good pH and thermal stability, retained inhibitory activity during simulated gastrointestinal digestion, and exhibited concentration-dependent antioxidant activities. LC-MS/MS identified 927 peptides, mainly low-molecular-weight short peptides enriched in proline and hydrophobic residues. A stepwise in silico screening strategy based on abundance, predicted bioactivity, safety, solubility, and ADMET properties narrowed the peptide pool to 22 candidates. Molecular docking suggested that several peptides could interact with key DPP-IV recognition residues through hydrogen bonding and hydrophobic interactions. Among the synthesized peptides, GPA showed the strongest DPP-IV inhibitory activity, with an IC 50 value of 0.464 mg/mL, whereas PGAGF was the most active peptide selected through the virtual screening workflow, with an IC 50 value of 10.449 mg/mL. Kinetic analysis indicated reversible competitive inhibition, and molecular dynamics simulations supported stable PGAGF-DPP-IV and GPA-DPP-IV binding. Overall, fish maw collagen is a promising source of DPP-IV inhibitory peptides for glycemic regulation-oriented food applications.

CAS / MDL: 54249-88-6
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