Foods
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2024
·Vol. 13
·期 8
·1194
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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
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药理学
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食品科学
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分子生物学
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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
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生物化学
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糖尿病研究
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植物化学
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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
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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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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
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