JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2021
·
IF 5.279
Ritian Jin,Jiaqi Shang,Xiangyu Teng,Ligang Zhang,Minhe Liao,Jiaxin Kang,Ran Meng,Dangfeng Wang,Haowei Ren,Ning Liu
Here, we characterize the activities of two depeptidyl peptidase-IV (DPP-IV) inhibitory peptides, VLATSGPG and LDKVFER, using the Caco-2 monolayer model for the intestine. VLATSGPG and LDKVFR inhibited the DPP-IV in the cells via a mixed-type inhibition mode, with in situ IC50 values of 207.3 and 148.5 μM, respectively. Furthermore, VLATSGPG and LDKVFR were transported intact across the cells, with Papp values of 2.41 ± 0.16 and 4.23 ± 0.29 × 10–7 cm/s, respectively. Fragmented peptides were identified in the basolateral side of the membrane. Two of these, GPG and VLA, exhibited high inhibitory activities of 83.6 ± 3.3 and 58.5 ± 2.5%, respectively, at 100 μM concentration. Although 3 mM VLATSGPG and LDKVFR were transported across the epithelium in a concentration-dependent manner, their transport did not damage the tight junction proteins, ZO-1 and occludin. This study demonstrates that the two peptides potentially regulate DPP-IV activity in the intestine.
研究领域:
生物化学
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药理学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Yuyang Liu,Yan Zhang,Minghao Liu,Sainan Yu,Zhenglin Tian,Wannan Li,Weiwei Han
Dipeptidyl peptidase-IV (DPP-IV) inhibitors play a critical role in the treatment of diabetes and metabolic diseases. This study combines computational simulations with experimental validation to identify peptides with potential DPP-IV inhibitory activity from wheat proteins. A peptide database was constructed through trypsin digestion simulation, and screening was performed using the ConPLex deep learning algorithm, leading to the identification of four promising peptides: TENEWK (Thr-Glu-Asn-Glu-Trp-Lys), NFVSER (Asn-Phe-Val-Ser-Glu-Arg), LDLPSK (Leu-Asp-Leu-Pro-Ser-Lys) and QHEQR (Gln-His-Glu-Gln-Arg). Experimental results showed that the IC50 values of these four peptides were 4.96 mM, 3.07 mM, 2.89 mM, and 4.18 mM, respectively, and they were all competitive DPP-IV inhibitors with significant inhibitory activity. Molecular dynamics (MD) simulations revealed the inhibitory mechanism by which inhibitory peptides led to the disappearance of the α-helix of the DPP-IV active center. Further tau-random accelerated molecular dynamics (tau-RaMD) simulations were used to calculate the binding residence time of each peptide, providing insights into their binding stability and key interacting residues. The combination of computational and experimental approaches significantly improved the accuracy and efficiency of screening peptides with DPP-IV inhibitory potential, providing a promising research foundation for developing peptide-enriched health foods.
研究领域:
生物化学
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计算生物学
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药理学
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食品科学
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DOI
PubMed
高影响因子
Food Bioscience
·
2025
·
IF 5.9
Yuxiang Gu,Yajie Niu,Yanbo Wang,Baoguo Sun,Shuxing Chen,Lishui Chen,Hao Dong,Yuyu Zhang
This study investigated the DPP-IV inhibitory activity of taste-modulating peptides from porcine bone and elucidated their inhibitory mechanisms. Sensory evaluation identified seven peptides with effects on umami taste or saltiness enhancement. Computational tools predicted that they all possessed DPP-IV inhibitory potential. Post-digestion, GPTAANRM, GPGCKAGL, NLRDNYRF and GVNAMLRK exhibited superior DPP-IV inhibition (IC 50 : 206.16 - 317.59 μmol/L). Molecular docking revealed that all these four peptides interacted with active residues in S1, S2 and S3 pocket of DPP-IV and the Lineweaver-Burk plots indicated their competitive inhibition mechanism. All these peptides alleviated insulin resistance in HepG2 cells to some extent, with GPTAANRM and GPGCKAGL notably reducing the blood glucose curve area in C57BL/6J mice. This research enhances our understanding of the beneficial role of taste-modulating peptides in diabetes management and suggests their potential in developing dietary strategies to optimize glycemic control in diabetic individuals.
研究领域:
生物化学
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食品科学
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药理学
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分子生物学
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营养学
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糖尿病研究
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高影响因子
JOURNAL OF APPLIED PHYCOLOGY
·
2022
·Vol. 34
·期 3
·1497-1511
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IF 3.404
Liu Jing,Bai Xinpeng,Fu Pengcheng
Arthrospira platensis proteins are considered as viable ingredients for functional foods with nutraceutical properties and health-promoting effects. In this study, we used five different proteases including pepsin, trypsin, alcalase, papain, and bromelain to hydrolyze A. platensis phycobiliprotein. LC–MS/MS (liquid chromatography-tandem mass spectrometry) was used to determine the composition of the hydrolysates with thousands of bioactive peptides. Based on peptide sequencing, a candidate list of 1,333 bioactive peptides was constructed for the first time for which bioinformatics tools were used to assess the properties of the bioactive peptides. The inhibitory activity of dipeptidyl peptidase IV (DPP-IV) and angiotensin-converting enzyme (ACE), as well as the antioxidant activity of five phycobiliprotein hydrolysates (PBPHs), were verified in vitro. The IC 50 values of PBPH-pepsin, PBPH-trypsin, PBPH-alcalase, PBPH-papain, and PBPH-bromelain for DPP-IV inhibited activity were determined to be 4.059, 5.603, 5.257, 3.819, and 4.195 mg mL −1 , respectively. All the above five PBPHs were also seen to significantly inhibit ACE activity ( P < 0.0001) in the range of 0.1–1.0 mg mL −1 . The activity of five PBPHs fraction was found for the 2-azino-bis (3-ethylbenzothiazoline6-sulfonic acid) diammonium salt (ABTS) assay (the highest was 1.37 mM Trolox equivalent of 30 mg mL −1 of PBPH-trypsin), 1,1diphenyl-2-picrylhydrazyl (DPPH) assay (the highest was 204.67 µM Trolox equivalent of 10 mg mL −1 of PBPH-pepsin), and Fe 2+ chelating ability (the highest was 639.73 µM FeSO 4 equivalent of 10 mg mL −1 of PBPH-trypsin). This study indicated that it was feasible to utilize A. platensis phycobiliprotein as a source of bioactive peptides which may be used as functional food and/or nutritional supplements for human health.
研究领域:
食品科学
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生物化学
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营养学
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药理学
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DOI
高影响因子
npj Science of Food
·
2025
·Vol. 9
·期 1
·224
·
IF 7.8
He Yi,Zhang Yan,Zhang Pengying,Li Jiaying,Li Wannan,Han Weiwei
Type 2 diabetes mellitus (T2DM) poses a significant global health burden, with dipeptidyl peptidase-IV (DPP-IV) inhibitors being critical therapeutic targets for its management. Malt, a natural medicinal food, shows promise for T2DM treatment, yet its active compounds need further exploration. This study integrates molecular docking (Libdock, Autodock Vina), deep learning models (ConPlex, KPGT), molecular dynamics (MD) simulations, and network pharmacology to identify and validate DPP-IV inhibitors from malt. The pentapeptide YPQPQ, derived from malt hordein, exhibited potent DPP-IV inhibition (IC 50 : 23.87 μM) in vitro. Network pharmacology identified MAPK1 and MAPK3 (ERK1 and ERK2) as key targets, with YPQPQ significantly reducing ERK phosphorylation. Molecular dynamics (MD) simulations revealed YPQPQ’s binding similarity to Diprotin A. These findings establish YPQPQ as a novel natural DPP-IV inhibitor, modulating the ERK signaling pathway, offering potential for T2DM therapy.
研究领域:
药理学
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计算生物学
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营养科学
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糖尿病研究
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生物信息学
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DOI
PubMed
高影响因子
INTERNATIONAL DAIRY JOURNAL
·
2026
·
IF 3.1
Shengnan Liang,Jiarui Li,Chun Li,Libo Liu,Peng Du,Guofang Zhang,Jian He
The hydrolysate of β-casein generated by bromelain exhibits potent DPP-IV inhibitory activity. • β-Casein hydrolysate significantly increased glucose consumption in insulin-resistant HepG2 cells. • MPIQAF, a β-casein-derived Xaa-Pro motif peptide, inhibits DPP-IV and alleviates glucose metabolism disorders. Bioactive peptides have shown therapeutic potential for type 2 diabetes by inhibiting dipeptidyl peptidase-IV (DPP-IV). In this study, β-casein (β-CN) hydrolysates were prepared using enzymatic hydrolysis and characterized spectroscopically, followed by activity analysis. The results showed that the particle size and surface hydrophobicity of β-CN were significantly reduced after enzymatic hydrolysis ( p < 0.05). Fluorescence spectroscopy revealed a red shift in the maximum emission wavelength, and secondary structure analysis indicated a conformational transition toward random coils and β-turns. Bromelain hydrolysate inhibited DPP-Ⅳ activity and significantly increased glucose consumption and glycogen synthesis in IR-HepG2 cells ( p < 0.05). A total of 439 peptide sequences were identified from the bromelain hydrolysate, among which 34.40% had a bioactivity score above 0.5, and most showed potential DPP-IV inhibitory ability. Through in silico analysis, the Xaa-Pro-type peptide MPIQAF was screened and showed strong binding affinity with DPP-IV, suggesting its hypoglycemic potential. MPIQAF was further synthesized and experimentally validated, and its direct DPP-IV inhibitory IC 50 was determined to be 2.832 mM. The peptide could ameliorate insulin resistance-induced glucose metabolism disorders in a dose-dependent manner and significantly reduce DPP-IV levels (p < 0.05). In summary, the bromelain hydrolysate, as a multi-peptide mixture, exhibited stronger overall DPP-IV inhibitory activity and holds promise for direct application as a functional food ingredient. The purified peptide MPIQAF, although a weak direct inhibitor, provides a valuable lead compound for mechanistic studies and future structural optimization toward glucose regulation. Download: Download high-res image (345KB) Download: Download full-size image
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DOI
高影响因子
Food Bioscience
·
2026
·
IF 6.2
Jia Ran,Zeyuan Yu,Xia Liu,Mingqian Wang,Yuxin Tang,Fujian Chen,Xiaodong Yu,Qiyi He
Dipeptidyl peptidase-IV (DPP-IV) is a key therapeutic target for type 2 diabetes, and food-derived inhibitory peptides are promising alternatives to synthetic drugs. In this study, bullfrog muscle protein hydrolysates were prepared using different proteases, among which the compound protease hydrolysate showed the strongest DPP-IV inhibitory activity. Ultrafiltration revealed that the <3 kDa fraction exhibited the highest potency. Three peptides (VPVG, LPVQ, and VPLG) were identified by LC–MS/MS combined with in silico screening. Among them, synthesized VPVG showed the strongest inhibitory activity (IC 50 = 128.91 μM). Enzyme kinetics indicated a mixed-type inhibition mechanism, while molecular docking and molecular dynamics simulations demonstrated stable interactions with the DPP-IV active site. The peptides showed good stability under heat treatment, varying pH conditions, and simulated gastrointestinal digestion. They exhibited no cytotoxicity in Caco-2 cells, inhibited cellular DPP-IV activity, and significantly reduced blood glucose levels in a hyperglycemic zebrafish model.
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高影响因子
Marine Drugs
·
2025
·Vol. 23
·期 6
·226
·
IF 5.4
Rui Liu,Wen-Jie Cao,Wen-Xiao Zhao,Xiao-Jie Yuan,Yu-Zhong Zhang,Qi-Long Qin,Xiao-Yan Song,Xi-Ying Zhang,Jian Li,Xiu-Lan Chen,Yu-Qiang Zhang
Antarctic krill (Euphausia superba) is a nutrient-rich marine resource. Although several terrestrial proteases have been used to prepare Antarctic krill peptides (AKPs), there has been no report on the preparation of AKPs using a marine protease. Here, marine bacterial protease A69 was used to prepare AKPs with multi-bioactivities. Through optimizing hydrolysis parameters, we established a process for AKPs preparation by hydrolyzing Antarctic krill powder with A69. In the prepared AKPs, peptides less than 3000 Da and 1000 Da accounted for 99.23% and 88.37%, respectively. The scavenging ratios of the AKPs to ABTS+, DPPH· and ·OH reached 93.23 ± 0.09%, 99.90 ± 0.15%, and 93.90 ± 0.47%, respectively. The AKPs also had high angiotensin-converting enzyme (ACE)-inhibitory activity, with an IC50of 0.22 ± 0.04 mg/mL. At 40 mg/mL, the AKPs inhibited α-glucosidase and dipeptidyl peptidase IV (DPP-IV) activities by 7.18% and 13.62%, respectively, and displayed antibacterial activity toEscherichia coli. Moreover, 14 antioxidant peptides, 24 ACE-inhibitory peptides, 2 α-glucosidase-inhibitory peptides, and 10 DPP-Ⅳ-inhibitory peptides were identified from the AKPs. These results demonstrate that the prepared AKPs contain diverse bioactive peptides and have multi-bioactivities. This study indicates that marine bacterial protease A69 has promising application potential in preparing AKPs with multi-bioactivities.
研究领域:
海洋生物学
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食品科学
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生物化学
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DOI
PubMed
高影响因子
Food & Function
·
2021
·Vol. 12
·期 21
·10773-10782
·
IF 5.396
Ritian Jin,Haowei Ren,Minhe Liao,Jiaqi Shang,Dangfeng Wang,Meng Li,Ning Liu
The peptide VLATSGPG (VLA) is known to inhibit dipeptidyl peptidase IV (DPP-IV), although its mechanism in relieving endoplasmic reticulum (ER) stress is unclear. In this study, we found that treating HepG2 cells with 1.0 mM VLA reduced DPP-IV activity by 73.7 ± 4.8% without changing the DPP-IV mRNA expression level. In addition, 1.0 and 0.5 mM VLA alleviated palmitic acid (PA)-induced cell death and intracellular calcium imbalances. The levels of apoptosis-related proteins (caspase-3, caspase-9, and CHOP) were reduced by VLA treatment, which was presumed to be related to ER stress. Further studies confirmed that VLA alleviated PA-induced morphological damage to the ER and reduced the levels of the ER stress marker proteins (BIP, p-PERK, and p-IRE1α). VLA alleviated PA-induced ER stress in HepG2 cells independent of DPP-IV enzymatic activity inhibition. These findings have implications for developing novel treatment approaches for liver diseases caused by ER stress.
研究领域:
分子生物学
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细胞生物学
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药理学
·
肝病
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产品关联
DOI
PubMed
高影响因子
Marine Drugs
·
2025
·Vol. 23
·期 8
·331
·
IF 5.4
Zhimin Zhu,Yan Zhang,Bingbing He,Limin He,Guihong Fang,Yi Ning,Pengcheng Fu,Jing Liu
Phycobiliproteins have gained increasing attention for their antidiabetic potential, yet the specific bioactive peptides and their targets and molecular mechanisms have remained unclear. In this study, four peptides with potential hypoglycemic activity were identified through virtual screening. Network pharmacology was employed to elucidate their hypoglycemic mechanism in the treatment of T2DM. A subsequent in vitro assay confirmed that the synthesized peptides, GR-5, SA-6, VF-6, and IR-7, exhibited significant inhibitory activity against α-glucosidase and DPP-IV. In insulin-resistant HepG2 models, all four peptides exhibited no cytotoxicity. Among them, GR-5 demonstrated the most promising therapeutic potential by remarkably enhancing cellular glucose consumption capacity. Furthermore, GR-5 administration substantially increased glycogen synthesis and enzymatic activities of hexokinase and pyruvate kinase with statistically significant improvements compared to the control groups. This study provides novel peptide candidates for T2DM treatment and validates an integrative strategy for targeted bioactive peptide discovery, advancing the development of algal protein-based therapeutics.
研究领域:
药学
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生物信息学
·
分子生物学
·
营养学
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糖尿病研究
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产品关联
DOI
PubMed
高影响因子
Foods
·
2026
·Vol. 15
·期 2
·398
·
IF 5.1
Jingjie Tan,Sirong Huang,Dongjing Wu,Zhongquan Zhao,Yongju Zhao,Yu Fu,Wei Wu
To enhance the screening efficiency of bioactive peptides, an AI-driven approach was employed to screen DPP-IV inhibitory peptides from goat blood proteins by an integratedin silico,in vitro, and machine learning strategy. Furthermore, the inhibitory mechanism of DPP-IV inhibitory peptides was elucidated by kinetics, molecular docking and simulation. Additionally, theirin vitrodigestive stability was assessed.In silicoresults revealed that goat blood proteins were promising precursors of DPP-IV inhibitory peptides, while bromelain was the optimal protease. Their peptide sequences were further identified by peptidomics and predicted by self-developed machine learning models (LightGBM) to identify the potent DPP-IV inhibitory peptides. Two novel DPP-IV inhibitory peptides were identified (FPL and FPHFDL). Enzyme kinetics, molecular docking and molecular simulation data indicated that FPL served as a competitive inhibitor, whereas FPHFDL was a non-competitive inhibitor. Overall, the integrativein silicoandin vitrostrategy is feasible for rapid screening of DPP-IV inhibitory peptides from goat blood proteins.
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DOI
PubMed
高影响因子
Food Bioscience
·
2026
·
IF 6.2
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.
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高影响因子
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