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...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):206.16-317.59μmol/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/6 J 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.展开更多
In recent years,bioactive peptides targeting dipeptidyl peptidase-IV(DPP-IV)have emerged as promising candidates for managing type 2 diabetes.This study aimed to screen novel DPP-IV inhibitory(DPP-IVi)peptides from ra...In recent years,bioactive peptides targeting dipeptidyl peptidase-IV(DPP-IV)have emerged as promising candidates for managing type 2 diabetes.This study aimed to screen novel DPP-IV inhibitory(DPP-IVi)peptides from rabbit meat proteins using a combined approach of in silico study and in vitro experiments,with a focus on elucidating their molecular mechanisms.Initially,enzymatic simulation and virtual screening identified three potential DPP-IVi peptides.Among these,the tetrapeptide IPVK exhibited the strongest inhibitory activity(IC50=152.9±14.55μM),demonstrating competitive inhibition in vitro.Additionally,IPVK displayed robust resilience under diverse conditions,including variations in temperature,pH,and gastrointestinal digestion.Further analysis using molecular docking revealed IPVK’s interaction with critical residues within the S1,S2 pockets,and catalytic triad of DPP-IV through hydrogen bonds and hydrophobic interactions.Molecular dynamics simulations confirmed the stable formation of the IPVK-DPP-IV complex,providing insight into the peptide’s stability and binding affinity.Moreover,the highest occupied molecular orbital(HOMO)analysis highlighted isoleucine and proline as essential components for IPVK’s bioactivity.Supporting these findings,IPVK effectively inhibited native DPP-IV in Caco-2 cells(IC50=287.40±29.50μM)and exhibited hypoglycemic effects in vivo in mice.In summary,this study presents an efficient method for screening and identifying DPP-IVi peptides.The discovery of IPVK highlights rabbit meat proteins as a potential source of DPP-IV inhibitors,establishing a robust theoretical basis for its application in the management of type 2 diabetes.展开更多
The objective of this study was to isolate and purify DPP-IV inhibitory(DPP-IVi)peptides from rabbit meat hydrolysate(RMH)and explore their mechanism of action,stability,and hypoglycemic effects.Various pro-teases,inc...The objective of this study was to isolate and purify DPP-IV inhibitory(DPP-IVi)peptides from rabbit meat hydrolysate(RMH)and explore their mechanism of action,stability,and hypoglycemic effects.Various pro-teases,including pepsin,alcalase,compound proteinase,flavourzyme,and bromelain,were utilized to prepare RMH,with RMH derived from the compound proteinase demonstrating the highest DPP-IV inhibition activity.Employing gel filtration chromatography,RP-HPLC and UPLC-MS/MS,we identified Leucyl-Leucine(LL),a dipeptide exhibiting potent DPP-IV inhibitory activity(IC_(50)=99.85±5.45μM).LL exhibited resistance to simulated gastrointestinal digestion in vitro and competitively inhibited DPP-IV.Molecular docking analysis revealed LL’s formation of hydrogen bonds and hydrophobic interactions with key amino acid residues of DPP-IV.Furthermore,LL exhibits good inhibitory activity in situ against DPP-IV.,with an IC_(50) value of 207.40±21.50μM.In an oral glucose tolerance test(OGTT),LL displayed significant hypoglycemic effects at 30 min after administration.In conclusion,LL derived from rabbit meat hydrolysate exhibited remarkable DPP-IV inhibition activity and hypoglycemic effects,suggesting its potential as a therapeutic candidate for diabetes treatment.展开更多
Food-derived dipeptidyl peptidase IV(DPP-IV)inhibitors show promise as a therapeutic intervention for type 2 diabetic mellitus(T2DM).This investigation used a combination of virtual screening and enzymatic digestion t...Food-derived dipeptidyl peptidase IV(DPP-IV)inhibitors show promise as a therapeutic intervention for type 2 diabetic mellitus(T2DM).This investigation used a combination of virtual screening and enzymatic digestion to prepare and identify novel DPP-IV inhibitory peptides from Esox lucius,a typical cold-water fish from Xinjiang.Alkaline protease digest showed the best inhibitory effect of 62.04%±1.07%.The ultrafiltration U1(<3 kDa)fraction had the best inhibitory activity with an IC_(50) value of 2.77±0.09 mg/mL.From the dextran gel chromatography S2 fraction,543 peptide fragments were found,and six peptides underwent virtual screening.Among them,APDPF showed promising DPP-IV inhibitory activity with an IC_(50) value of 0.38±0.02 mg/mL and exhibited competitive inhibition of DPP-IV by binding to amino acid residues in the S1 and S2 active pockets by forming hydrogen bonds and hydrophobic forces.This study provides a new way to prepare DPP-IV inhibitory peptide and is of great theoretical significance and practical value for further exploring the development of endogenous peptides from Esox lucius.展开更多
The use of green and low-cost techniques to produce bioactive peptides with anti-diabetic properties from protein-rich fish waste is a sustainable way to manage agro-fishery and food industrial waste.This study invest...The use of green and low-cost techniques to produce bioactive peptides with anti-diabetic properties from protein-rich fish waste is a sustainable way to manage agro-fishery and food industrial waste.This study investigated a novel ultrasound(UL)assisted deep eutectic solvent(DES)based extraction approach to recover bioactive protein-rich extracts from tilapia fish viscera waste under optimized conditions(52.52%ultrasound amplitude,1:4 DES molar ratio,25 min extraction time).The aqueous two-phase system(ATPS)method suc-cessfully concentrated the crude proteins in the top phase and back-extracted proteins to the bottom phase with a high recovery yield.Hydrolysis by Alcalase produced tilapia viscera protein hydrolysate(TVPH)with low mo-lecular weight(MW)peptides and low dipeptidyl peptidase(DPP)-IV half-maximal inhibitory concentration(IC_(50))value of 1.57±0.16 mg/mL.Notably,TVPH-3 fraction and TVPH-3-2 sub-fraction exhibited appreciable DPP-IV IC_(50) values of 1.36±0.08 mg/mL and 0.42±0.01 mg/mL,respectively.Ultrafiltration combined with RP-HPLC enriched the DPP-IV inhibitory concentration of the individual protein fractions.TVPH-3-2 sub-fraction contained hydrophobic amino acids and peptide sequences with typical DPP-IV inhibitory peptide sequence motifs.The results presented in this study indicate that tilapia viscera biomass is a potential source for protein recovery aided with a green extraction approach,and tilapia viscera protein-derived hydrolysates have potential applications as a potent functional food ingredient for the management of metabolic diseases like type-2 diabetes.展开更多
This study focused on the enzymatic characteristics,with regard to primary specificity,secondary specificity,and hydrolysis ability of five proteases(Alcalase,Protamex,papain,Flavourzyme,and ProtexA),towards the relea...This study focused on the enzymatic characteristics,with regard to primary specificity,secondary specificity,and hydrolysis ability of five proteases(Alcalase,Protamex,papain,Flavourzyme,and ProtexA),towards the release of dipeptidyl peptidase-IV(DPP-IV)inhibitory peptides from bovine casein.The secondary specificity of the five proteases,especially the release capability for Xaa-Pro-type peptide played a determining role in the release of DPP-IV inhibitory peptides from bovine casein.Moreover,protease combinations,chosen based on their Xaa-Pro-type peptide release abilities,resulted in superior DPP-Ⅳ inhibitory activity compared to other combinations.Particularly,the hydrolysate with the highest DPP-IV inhibitory activity(IC_(50) value of 0.45±0.07 mg/mL)was obtained by the combination hydrolysis of ProtexA and papain,achieving a 74.63%±1.62%(peak area)release of Xaa-Pro-type peptide,and a significant improving glucose tolerance in mice(33.42%±1.68%reduction of blood glucose AUC compared with control mice).The mechanistic insights revealed that papain efficiently released long Xaa-Pro-type peptides in the early hydrolysis stage,and subsequently,the synergistic effect of papain and ProtexA led to an accelerated and extensive release of short Xaa-Pro-type peptides.These findings provide valuable insight into enzymatic processes for generating DPP-IV inhibiting peptides from casein.展开更多
基金supported by the National Natural Science Foundation of China(Nos.32402278 and 32372463).
文摘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):206.16-317.59μmol/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/6 J 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.
基金supported by Chongqing Forestry Reform and Development Fund(grant number Yu-lin-ke-tui-2019-2)Chongqing Normal University Fund projects(grant number 19XLB006).
文摘In recent years,bioactive peptides targeting dipeptidyl peptidase-IV(DPP-IV)have emerged as promising candidates for managing type 2 diabetes.This study aimed to screen novel DPP-IV inhibitory(DPP-IVi)peptides from rabbit meat proteins using a combined approach of in silico study and in vitro experiments,with a focus on elucidating their molecular mechanisms.Initially,enzymatic simulation and virtual screening identified three potential DPP-IVi peptides.Among these,the tetrapeptide IPVK exhibited the strongest inhibitory activity(IC50=152.9±14.55μM),demonstrating competitive inhibition in vitro.Additionally,IPVK displayed robust resilience under diverse conditions,including variations in temperature,pH,and gastrointestinal digestion.Further analysis using molecular docking revealed IPVK’s interaction with critical residues within the S1,S2 pockets,and catalytic triad of DPP-IV through hydrogen bonds and hydrophobic interactions.Molecular dynamics simulations confirmed the stable formation of the IPVK-DPP-IV complex,providing insight into the peptide’s stability and binding affinity.Moreover,the highest occupied molecular orbital(HOMO)analysis highlighted isoleucine and proline as essential components for IPVK’s bioactivity.Supporting these findings,IPVK effectively inhibited native DPP-IV in Caco-2 cells(IC50=287.40±29.50μM)and exhibited hypoglycemic effects in vivo in mice.In summary,this study presents an efficient method for screening and identifying DPP-IVi peptides.The discovery of IPVK highlights rabbit meat proteins as a potential source of DPP-IV inhibitors,establishing a robust theoretical basis for its application in the management of type 2 diabetes.
基金supported by Chongqing Forestry Reform and Development Fund(grant number Yu-lin-ke-tui-2019-2)the Project of Chongqing Science and Technology Bureau(grant number cstc2017chmsxdny0246).
文摘The objective of this study was to isolate and purify DPP-IV inhibitory(DPP-IVi)peptides from rabbit meat hydrolysate(RMH)and explore their mechanism of action,stability,and hypoglycemic effects.Various pro-teases,including pepsin,alcalase,compound proteinase,flavourzyme,and bromelain,were utilized to prepare RMH,with RMH derived from the compound proteinase demonstrating the highest DPP-IV inhibition activity.Employing gel filtration chromatography,RP-HPLC and UPLC-MS/MS,we identified Leucyl-Leucine(LL),a dipeptide exhibiting potent DPP-IV inhibitory activity(IC_(50)=99.85±5.45μM).LL exhibited resistance to simulated gastrointestinal digestion in vitro and competitively inhibited DPP-IV.Molecular docking analysis revealed LL’s formation of hydrogen bonds and hydrophobic interactions with key amino acid residues of DPP-IV.Furthermore,LL exhibits good inhibitory activity in situ against DPP-IV.,with an IC_(50) value of 207.40±21.50μM.In an oral glucose tolerance test(OGTT),LL displayed significant hypoglycemic effects at 30 min after administration.In conclusion,LL derived from rabbit meat hydrolysate exhibited remarkable DPP-IV inhibition activity and hypoglycemic effects,suggesting its potential as a therapeutic candidate for diabetes treatment.
基金funded by XPCC Key areas Science and Technology Program of China(grant number 2023AB006-04)XPCC Guiding Science and Technology Program of China(grant number 2022DZ016)+2 种基金High-level Talent Initiation Program of Shihezi University(grant number RCZK202355)Key Laboratory for Nutrition and Safety of Xinjiang Specialty Foods,Shihezi City of Eighth Division(grant number 2022PT02)Research Program of Shihezi University(grant number PYZK202405).
文摘Food-derived dipeptidyl peptidase IV(DPP-IV)inhibitors show promise as a therapeutic intervention for type 2 diabetic mellitus(T2DM).This investigation used a combination of virtual screening and enzymatic digestion to prepare and identify novel DPP-IV inhibitory peptides from Esox lucius,a typical cold-water fish from Xinjiang.Alkaline protease digest showed the best inhibitory effect of 62.04%±1.07%.The ultrafiltration U1(<3 kDa)fraction had the best inhibitory activity with an IC_(50) value of 2.77±0.09 mg/mL.From the dextran gel chromatography S2 fraction,543 peptide fragments were found,and six peptides underwent virtual screening.Among them,APDPF showed promising DPP-IV inhibitory activity with an IC_(50) value of 0.38±0.02 mg/mL and exhibited competitive inhibition of DPP-IV by binding to amino acid residues in the S1 and S2 active pockets by forming hydrogen bonds and hydrophobic forces.This study provides a new way to prepare DPP-IV inhibitory peptide and is of great theoretical significance and practical value for further exploring the development of endogenous peptides from Esox lucius.
基金the National Kaohsiung University of Science and Technology,Kaohsiung City,Taiwan for technical supportsupported by the National Science and Technology Council(NSTC)project,Taiwan(Ref.No.112-2222-E-992-005)Cheng-Di Dong also acknowledges the Taiwan MOST for funding support(Ref.No.109-2222-E-992-002).
文摘The use of green and low-cost techniques to produce bioactive peptides with anti-diabetic properties from protein-rich fish waste is a sustainable way to manage agro-fishery and food industrial waste.This study investigated a novel ultrasound(UL)assisted deep eutectic solvent(DES)based extraction approach to recover bioactive protein-rich extracts from tilapia fish viscera waste under optimized conditions(52.52%ultrasound amplitude,1:4 DES molar ratio,25 min extraction time).The aqueous two-phase system(ATPS)method suc-cessfully concentrated the crude proteins in the top phase and back-extracted proteins to the bottom phase with a high recovery yield.Hydrolysis by Alcalase produced tilapia viscera protein hydrolysate(TVPH)with low mo-lecular weight(MW)peptides and low dipeptidyl peptidase(DPP)-IV half-maximal inhibitory concentration(IC_(50))value of 1.57±0.16 mg/mL.Notably,TVPH-3 fraction and TVPH-3-2 sub-fraction exhibited appreciable DPP-IV IC_(50) values of 1.36±0.08 mg/mL and 0.42±0.01 mg/mL,respectively.Ultrafiltration combined with RP-HPLC enriched the DPP-IV inhibitory concentration of the individual protein fractions.TVPH-3-2 sub-fraction contained hydrophobic amino acids and peptide sequences with typical DPP-IV inhibitory peptide sequence motifs.The results presented in this study indicate that tilapia viscera biomass is a potential source for protein recovery aided with a green extraction approach,and tilapia viscera protein-derived hydrolysates have potential applications as a potent functional food ingredient for the management of metabolic diseases like type-2 diabetes.
基金supported by the National Natural Science Foundation of China(32172134)the Guangdong Natural Science Foundation for Distinguished Young Scholars(2023B1515020023).
文摘This study focused on the enzymatic characteristics,with regard to primary specificity,secondary specificity,and hydrolysis ability of five proteases(Alcalase,Protamex,papain,Flavourzyme,and ProtexA),towards the release of dipeptidyl peptidase-IV(DPP-IV)inhibitory peptides from bovine casein.The secondary specificity of the five proteases,especially the release capability for Xaa-Pro-type peptide played a determining role in the release of DPP-IV inhibitory peptides from bovine casein.Moreover,protease combinations,chosen based on their Xaa-Pro-type peptide release abilities,resulted in superior DPP-Ⅳ inhibitory activity compared to other combinations.Particularly,the hydrolysate with the highest DPP-IV inhibitory activity(IC_(50) value of 0.45±0.07 mg/mL)was obtained by the combination hydrolysis of ProtexA and papain,achieving a 74.63%±1.62%(peak area)release of Xaa-Pro-type peptide,and a significant improving glucose tolerance in mice(33.42%±1.68%reduction of blood glucose AUC compared with control mice).The mechanistic insights revealed that papain efficiently released long Xaa-Pro-type peptides in the early hydrolysis stage,and subsequently,the synergistic effect of papain and ProtexA led to an accelerated and extensive release of short Xaa-Pro-type peptides.These findings provide valuable insight into enzymatic processes for generating DPP-IV inhibiting peptides from casein.
