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
·
细胞生物学
·
药理学
·
肝病
✓ 已验证
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.
✓ 已验证
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
·
生物信息学
·
分子生物学
·
营养学
·
糖尿病研究
✓ 已验证
产品关联
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.
✓ 已验证
产品关联
DOI
高影响因子
Foods
·
2024
·Vol. 13
·期 8
·1194
·
IF 4.7
Yulong Wu,Jin Zhang,Ruikai Zhu,Hong Zhang,Dapeng Li,Huanhuan Li,Honggang Tang,Lihong Chen,Xinyan Peng,Xianrong Xu,Ke Zhao
Two novel dipeptidyl peptidase IV (DPP-IV) inhibitory peptides (YPF and LLLP) were discovered from goat milk protein by peptidomics, in silico analysis, and in vitro assessment. A total of 698 peptides (<23 AA) were successfully identified by LC-MS/MS from goat milk hydrolysates (hydrolyzed by papaian plus proteinase K). Then, 105 potential DPP-IV inhibitory peptides were screened using PeptideRanker, the ToxinPred tool, Libdock, iDPPIV-SCM, and sequence characteristics. After ADME, physicochemical property evaluation, and a literature search, 12 candidates were efficiently selected and synthesized in vitro for functional validation. Two peptides (YPF and LLLP) were found to exert relatively high in vitro chemical system (IC50= 368.54 ± 12.97 μM and 213.99 ± 0.64 μM) and in situ (IC50= 159.46 ± 17.40 μM and 154.96 ± 8.41 μM) DPP-IV inhibitory capacities, and their inhibitory mechanisms were further explored by molecular docking. Our study showed that the formation of strong non-bonding interactions with the core residues from the pocket of DPP-IV (such as ARG358, PHE357, GLU205, TYR662, TYR547, and TYR666) might primarily account for the DPP-IV inhibitory activity of two identified peptides. Overall, the two novel DPP-IV inhibitory peptides rapidly identified in this study can be used as functional food ingredients for the control of diabetes.
研究领域:
生物化学
·
药理学
·
食品科学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
·
2023
·
IF 2.65
Lei Zhang,Ming-yue Pan,Tao Li,Zhi-min Jin,Zhu Liu,Qiu-yue Liu,Yong Liu,Jia-yuan Ding,Huan Jiang,Xingchen Hou
Quercetin was extracted from Portulaca oleracea L. through biphasic acid hydrolysis to investigate its potential as a suppressor of dipeptidyl peptidase IV (DPP-IV) and its hypoglycemic effect in type 2 diabetic mice. The extraction procedure was optimized utilizing the response surface method (RSM) in a single-factor experimental setting. An extraction efficiency of 0.675% was achieved using the following optimized parameters: 0.064 mol/L vitriol, 1 : 109.155 solid-liquid ratio, and 21.408 min ultrasonication. Overall, findings indicate the effectiveness of quercetin extraction. A mouse model for type 2 diabetes was established to receive oral treatment with various quercetin concentrations for 8 weeks. Fasting blood glucose (FBG) and the DPP-IV activity in the serum were significantly reduced. The weight and insulin levels of the mice in the quercetin group were raised compared to those in the model group ( < 0.01). Quercetin dose-dependently inhibited postprandial blood glucose excursions, as demonstrated by the oral glucose tolerance test. These results confirmed that quercetin has hypoglycemic effects and considerably improves insulin sensitivity via DPP-IV targeting.
研究领域:
药理学
·
生物化学
·
糖尿病研究
·
植物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BMC Pharmacology & Toxicology
·
2024
·Vol. 25
·期 1
·1-15
·
IF 2.8
Wang Tianyan,Tao Ting,Liu Yi,Dong Jie,Ni Shanhong,Liu Yun,Li Yanli,Xu Ning,Sun Zengxian
Background and purposes It is unclear whether the parent Saxagliptin (SAX) in vivo is the same as that in vitro, which is twice that of 5-hydroxy Saxagliptin (5-OH SAX). This study is to construct a Pharmacokinetic-Pharmacodynamic (PK-PD) link model to evaluate the genuine relationship between the concentration of parent SAX in vivo and the effect. Methods First, we established a reliable Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS/MS) method and DPP-4 inhibition ratio determination method. Then, the T2DM rats were randomly divided into four groups, intravenous injection of 5-OH SAX (0.5 mg/kg) and saline group, intragastric administration of SAX (10 mg/kg) and Sodium carboxymethyl cellulose (CMC-Na) group. Plasma samples were collected at different time points for subsequent testing. Finally, we used the measured concentrations and inhibition ratios to construct a PK-PD link model for 5-OH SAX and parent SAX. Results A two-compartment with additive model showed the pharmacokinetic process of SAX and 5-OH SAX, the concentration-effect relationship was represented by a sigmoidal E max model and sigmoidal E max with E 0 model for SAX and 5-OH SAX, respectively. Fitting parameters showed SAX was rapidly absorbed after administration ( T max =0.11 h, t 1/2, ka =0.07 h), widely distributed in the body (V ≈ 20 L/kg), plasma exposure reached 3282.06 ng*h/mL, and the elimination half-life was 6.13 h. The maximum plasma dipeptidyl peptidase IV (DPP-4) inhibition ratio of parent SAX was 71.47%. According to the final fitting parameter EC 50 , EC 50, 5−OH SAX =0.46EC 50, SAX(parent) , it was believed that the inhibitory effect of 5-OH SAX was about half of the parent SAX, which is consistent with the literature. Conclusions The PK-PD link model of the parent SAX established in this study can predict its pharmacokinetic process in T2DM rats and the strength of the inhibitory effect of DPP-4 based on non-clinical data.
研究领域:
药理学
·
药代动力学
·
药效学
·
糖尿病研究
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
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
·
细胞生物学
·
药理学
·
生物化学
✓ 已验证
产品关联
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
·
内分泌学
·
糖尿病研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Energy Storage
·
2024
·
IF 8.9
Jing Huang,Jiang Peng,Junqing Zeng,Liping Zheng,Huajie Chen
Despite the important advances on B/N co-doped porous carbons (BNCs), integrating high B/N-doping content and hierarchical porosity into carbon nanosheets remains a challenging task for supercapacitor application. Herein, we report a novel BNC nanosheet with both expected properties through one-step H 3 BO 3 -mediated carbonization/activation of a newly-developed N/O-rich polymer (DPP). In such a mixture system, an in-suit crossing-linked DPP@H 3 BO 3 composite is formed due to the formation of multiple intermolecular hydrogen bonds between the H 3 BO 3 and the ester groups of DPP. The improved thermal stability for such a composite enables the fixation of more B-/N-bearing species in the carbon skeleton during carbonization. Particularly the nanosheet-like BNC-850 shows a rather high B/N content (6.63/7.27 at.%), a large S BET value (766.5 m 2 g −1 ), and a hierarchical porosity, all of which are in favor of electrochemical performance in both aqueous supercapacitors and zinc-ion capacitors (ZICs). In 6 M KOH electrolyte, the BNC-850 electrodes deliver an impressive capacitance of 341.5 F g −1 at 0.5 A g −1 , a high capacitance retention of 79.2 % at 20 A g −1 , and a good cycling stability (95 % capacitance retention over 10,000 cycles at 5 A g −1 ). The energy density of BNC-850-based ZICs is as high as 126.0 Wh kg −1 at 459.0 W kg −1 , exhibiting an outstanding superiority compared to the reported carbon-based ZICs. This work offers a facile strategy for accessing BNCs with high B/N-doping contents, and highlights the importance of such materials in high-energy-density ZICs.
研究领域:
材料科学
·
电化学
·
能源存储
✓ 已验证
产品关联
DOI
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
·
营养学
·
生物化学
·
药理学
·
糖尿病管理
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanophotonics
·
2018
·Vol. 7
·期 7
·1341-1350
·
IF 6.014
Jiangying Xia,Kang Xie,Jiajun Ma,Xianxian Chen,Yaxin Li,Jianxiang Wen,Jingjing Chen,Junxi Zhang,Sizhu Wu,Xusheng Cheng,Zhijia Hu
This paper systematically demonstrated a variety of experimental phenomena of random lasers (RLs) of N,N′-di-(3-(isobutyl polyhedral oligomeric silsesquioxanes)propyl) perylene diimide (DPP) organic/inorganic hybrid laser dye, which is composed of perylene diimide (PDI) as gain media and polyhedral oligomeric silsesquioxanes (POSS) as scattering media at a mole ratio of 1:2. In this work, we observe the transition from incoherent RL in the DPP-doped solutions and polymer membrane systems using dip-coating method to coherent RL in the polymer membrane system with defect waveguide using semi-polymerization (SP) coating method. Meanwhile, we found that the hybrid dye-DPP has a long lasing lifetime compared with the traditional laser dyes, which indicates that the POSS group can suppress the photo-bleaching effect to extend the working life of laser dyes.
研究领域:
光学
·
材料科学
·
光子学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）