JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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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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产品关联
DOI
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
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
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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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DOI
PubMed
高影响因子
JOURNAL OF APPLIED PHYCOLOGY
·
2022
·Vol. 34
·期 3
·1497-1511
·
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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产品关联
DOI
高影响因子
Journal of Functional Foods
·
2023
·
IF 5.6
Ritian Jin,Jude Juventus Aweya,Rong Lin,Wuyin Weng,Jiaqi Shang,Dangfeng Wang,Yiling Fan,Shen Yang
VLATSGPG (VLA) was a DPP-IV inhibitory peptide isolated from salmon ( Salmo Salar ) skin. Here, we demonstrated that VLA inhibited the activation of PERK through the AKT signaling pathway. Furthermore, we investigated the effect of VLA on free fatty acid (FFA)-induced lipid accumulation disorder and inflammation in HepG2 cells, elucidating the potential regulatory mechanism in this nonalcoholic fatty liver disease cell model. VLA reduced the mRNA expression of adipogenic factors FAS, ACC, and SCD-1 through the PERK/eIF2α pathway and the level of apolipoprotein B-100 secretion. These may contribute to the reducing FFA-induced lipid accumulation in cells and reducing intracellular lipid levels. In addition, VLA increased IκBα mRNA expression via the PERK/IκBα pathway, inhibited the NF-κB p65 activation, and thus inhibited cell inflammation.
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
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生物化学
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DOI
高影响因子
Scientific Reports
·
2017
·Vol. 7
·期 1
·1-11
·
IF 4.259
Ma Jie,Li Huan,Hu Xiangnan,Yang Lu,Chen Qi,Hu Congli,Chen Zhihao,Tian Xiaoyan,Yang Yang,Luo Ying,Gan Run,Yang Junqing
Dipeptidyl peptidase IV (DPP-IV) inhibitor has been expected to be a new class of anti-diabetic agent. The present study was designed to characterize the pharmacological profiles of CMD-05, a novel DPP-IV inhibitor discovered in our laboratory, in vitro and in vivo . The IC 50 of CMD-05 on DPP-IV inhibitory activity was approximately 12 nM while vildagliptin was 3.5 nM in vitro . In diabetes rat model established by high fat diet/low dose streptozotocin, CMD-05 inhibited DPP-IV activity, significantly improved glucose tolerance, increased GLP-1 and insulin levels in plasma. Long-term administration of CMD-05 decreased HbA1c and TG levels and improved the islet function without significantly effect on body weight. Furthermore, CMD-05 reduced INS-1 cell apoptosis and increased GLP-1 secretion in NCI-H716. After oral administration, CMD-05 reached peak concentration at 30 min with half-life of 288 minutes and the inhibitory rate of DPP-IV greater than 50% lasted for 15 h. In fasted normal rats, CMD-05 didn’t cause significant hypoglycemia. CMD-05 had a lower cytotoxicity than vildagliptin in vitro and its maximum tolerance dose in mice is beyond 2000 mg/kg. These results indicated that CMD-05 has similar activity with vildagliptin in vivo and has a much longer half-life and lower cytotoxicity than vildagliptin.
研究领域:
药理学
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内分泌学
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糖尿病研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF FOOD SCIENCE
·
2024
·
IF 3.2
Weijing Wu,Libo Wang,Ju Qiu,Ziyuan Zhuang,Fei Qin,Qianglai Tan,Yanling Wang,Lanlan Wu
Tartary buckwheat, a protein-rich pseudocereal with anti-diabetic effects, has not yet been fully explored as a source of dipeptidyl peptidase-IV (DPP-IV) inhibitory peptides. This study aims to discover novel DPP-IV inhibitory peptides from tartary buckwheat protein (TBP). Five hydrolysis methods were employed, with simulated gastrointestinal digestion (SGID) releasing the most active DPP-IV inhibitory hydrolysates, showing both the highest degree of hydrolysis (22.66 ± 1.12%) and inhibition activity (41.81 ± 1.52% at 1.25 mg/mL). In addition, ultrafiltration enriched the <3 kDa fraction with the highest inhibitory rate, and further purification using reverse-phase high-performance liquid chromatography concentrated the DPP-IV inhibitory peptides in the first fraction (F1). Nano liquid chromatography-tandem mass spectrometry analysis identified 10 new peptides in F1, among which the peptide Leu-His-Ile-Val-Gly-Pro-Asp-Lys (LHIVGPDK) exhibited the strongest inhibitory effect, with an IC 50 value of 1.61 mM. Kinetic studies revealed that LHIVGPDK acts as a mixed-type inhibitor, and molecular docking indicated that it inhibits DPP-IV by forming stable complexes through five types of interactions, with hydrogen bonds playing a key role. This study underscores TBP's DPP-IV inhibitory potential and anti-diabetic properties, reinforcing the value of tartary buckwheat as a beneficial food for diabetes management. Practical Application This research identified new peptides from Tartary buckwheat protein that effectively inhibit DPP-IV, an enzyme associated with diabetes management. These findings suggest potential applications in developing functional foods to help control hypoglycemia.
研究领域:
食品科学
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营养学
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生物化学
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药理学
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糖尿病管理
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）