Novel angiotensin-converting enzyme(ACE)inhibitory peptides were identified from whey protein hydrolysates(WPH)in vitro in our previous study and the antihypertensive abilities of WPH in vivo were further investigated...Novel angiotensin-converting enzyme(ACE)inhibitory peptides were identified from whey protein hydrolysates(WPH)in vitro in our previous study and the antihypertensive abilities of WPH in vivo were further investigated in the current study.Results indicated that WPH significantly inhibited the development of high blood pressure and tissue injuries caused by hypertension.WPH inhibited ACE activity(20.81%,P<0.01),and reduced renin concentration(P<0.05),thereby reducing systolic blood pressure(SBP)(12.63%,P<0.05)in spontaneously hypertensive rats.The increased Akkermansia,Bacteroides,and Lactobacillus abundance promoted high short chain fatty acid content in feces after WPH intervention.These changes jointly contributed to low blood pressure.The heart weight and cardiomyocyte injuries(hypertrophy and degeneration)were alleviated by WPH.The proteomic results revealed that 19 protein expressions in the heart mainly associated with the wingless/integrated(Wnt)signaling pathway and Apelin signaling pathway were altered after WPH supplementation.Notably,WPH alleviated serum oxidative stress,indicated by the decreased malondialdehyde content(P<0.01),enhanced total antioxidant capacity(P<0.01)and superoxide dismutase activity(P<0.01).The current study suggests that WPH exhibit promising antihypertensive abilities in vivo and could be a potential alternative for antihypertensive dietary supplements.展开更多
Nattokinase(NK),an alkaline serine protease,is recognized for its cardiovascular benefits through the modulation of blood coagulation and fibrinolytic pathways.Atherosclerosis(AS),a primary cause of cardiovascular dis...Nattokinase(NK),an alkaline serine protease,is recognized for its cardiovascular benefits through the modulation of blood coagulation and fibrinolytic pathways.Atherosclerosis(AS),a primary cause of cardiovascular disease(CVD)worldwide,is responsive to dietary interventions.However,studies investigating NK’s digestion,absorption,and mechanisms in mitigating AS remain limited.This study evaluated the effects of high-dose NK treatment(H-NK,900 FU/kg body weight)administered over six weeks in ApoE^(-/-) mice,which resulted in significant reductions in atherosclerotic lesions.In vitro digestion simulations showed that 25.8% of NK’s enzymatic activity was retained post-digestion,and thrombolysis assays demonstrated a thrombolytic efficacy of 30–40%at concentrations ≥5000μg/mL,regardless of clot age.Absorption experiments using a rat everted intestinal sac model revealed a small intestine absorption rate of 37.0%,with the absorbed peptides being predominantly hydrophobic,uncharged,and shorter than 10 amino acids.Proteomic analysis of mouse liver tissues identified that high-dose NK down-regulated PXDN(peroxidasin)and PNLIP(pancreatic lipase),proteins involved in promoting lipid oxidation,and intestinal lipid absorption.These proteomic changes enhanced lipid metabolism,reduced lipid peroxidation,and alleviated AS through the"Lipid and Atherosclerosis"pathway.Overall,this study provides a deeper understanding of NK’s biological activity and supports its potential as a novel dietary supplement for the management of CVD.展开更多
Immunosuppression is closely linked to intestinal barrier dysfunction and gut microbial imbalance.Our previous studies demonstrated that the Maillard reaction can effectively enhance the prebiotic function and antioxi...Immunosuppression is closely linked to intestinal barrier dysfunction and gut microbial imbalance.Our previous studies demonstrated that the Maillard reaction can effectively enhance the prebiotic function and antioxidant capacity of silver carp hydrolysates(SCH)in vitro,suggesting their potential immunomodulatory value.There-fore,this study investigated the prebiotic and immunomodulatory effects of Maillard reaction-modified silver carp hydrolysates(SCH-MRPs)in a cyclophosphamide-induced immunosuppression model.SCH-MRPs signifi-cantly improved both humoral and mucosal immunity by increasing serum immunoglobulins,normalizing colonic cytokine balance,and re-establishing CD4^(+)/CD8^(+)T-cell homeostasis.They also improved colon index,body weight,and colonic antioxidant capacity.Mechanistically,SCH-MRPs reactivated TLR4/NF-κB signaling,enhancing immune responsiveness,and reinforced intestinal barrier integrity through the upregulation of zonula occludens-1(ZO-1),Occludin,Claudin-1,and Muc-2.Additionally,SCH-MRPs reshaped the gut microbiota composition toward a more beneficial profile,characterized by enrichment of short chain fatty acid(SCFA)-producing bacteria such as Bacteroidetes and a reduction in potentially harmful genera like Candida-tus_Saccharimonas.These microbial shifts were accompanied by increased total SCFA levels,particularly propi-onic acid and butyric acid,along with upregulation of SCFA receptor expression.Overall,this study provides scientific evidence supporting SCH-MRPs as promising peptide-based prebiotic candidates for modulating gutimmune homeostasis and advancing functional food development.展开更多
Silver carp(Hypophthalmichthys molitrix)is a low-cost,protein-rich freshwater fish with high nutritional value but remains underutilized in functional food applications.Our previous studies have demonstrated that silv...Silver carp(Hypophthalmichthys molitrix)is a low-cost,protein-rich freshwater fish with high nutritional value but remains underutilized in functional food applications.Our previous studies have demonstrated that silver carp hydrolysates(SCH)possess potential in the management of chronic diseases and that their sensory properties and antioxidant activities can be further enhanced through Maillard reaction.However,the prebiotic potential of Maillard reaction-modified SCH has been rarely explored.This study investigates the prebiotic potential of SCH-based Maillard reaction products(SCH-MRPs)using in vitro fermentation model combined with 16S rRNA sequencing and metabolomics.During the fermentation process,moderate Maillard reaction significantly promoted SCFA production(approximately 16.29%)(p<0.05),particularly acetic,propionic,and butyric acids,which are known to play key roles in maintaining intestinal health and immune function.These changes were associated with increased microbial diversity,as indicated by higher Shannon(41.44%)and Simpson(18.30%)indices,along with a 264.24%increase in the relative abundance of Bacteroides.Metabolomics analysis revealed differential metabolites in the SCH-MRPs group suggested potential involvement in regulating tryptophan metabolism and bile secretion pathways,including indole-3-carboxaldehyde,indolepropionate,and glycochenodeoxycholic acid 3-glucuronide.Correlation analysis showed significant positive correlation between Fusobacterium,Bacteroides,and unidentified_Clostridiales abundances with indoles and derivatives,suggesting a regulatory role in tryptophan metabolism.This study systematically explores the prebiotic potential of Maillard reaction-modified SCH conjugated with oligosaccharides.By integrating microbial community analysis and metabolomics,it reveals a dual effect of SCH-MRPs in enhancing gut microbiota composition and metabolic activity,offering a promising strategy for microbiome-targeted functional food development.展开更多
基金supported by the Young Elite Scientists Sponsorship Program by CAST(2021QNRC001)。
文摘Novel angiotensin-converting enzyme(ACE)inhibitory peptides were identified from whey protein hydrolysates(WPH)in vitro in our previous study and the antihypertensive abilities of WPH in vivo were further investigated in the current study.Results indicated that WPH significantly inhibited the development of high blood pressure and tissue injuries caused by hypertension.WPH inhibited ACE activity(20.81%,P<0.01),and reduced renin concentration(P<0.05),thereby reducing systolic blood pressure(SBP)(12.63%,P<0.05)in spontaneously hypertensive rats.The increased Akkermansia,Bacteroides,and Lactobacillus abundance promoted high short chain fatty acid content in feces after WPH intervention.These changes jointly contributed to low blood pressure.The heart weight and cardiomyocyte injuries(hypertrophy and degeneration)were alleviated by WPH.The proteomic results revealed that 19 protein expressions in the heart mainly associated with the wingless/integrated(Wnt)signaling pathway and Apelin signaling pathway were altered after WPH supplementation.Notably,WPH alleviated serum oxidative stress,indicated by the decreased malondialdehyde content(P<0.01),enhanced total antioxidant capacity(P<0.01)and superoxide dismutase activity(P<0.01).The current study suggests that WPH exhibit promising antihypertensive abilities in vivo and could be a potential alternative for antihypertensive dietary supplements.
基金funded by the National Key Research and Development Program of China(2023YFF1103802).
文摘Nattokinase(NK),an alkaline serine protease,is recognized for its cardiovascular benefits through the modulation of blood coagulation and fibrinolytic pathways.Atherosclerosis(AS),a primary cause of cardiovascular disease(CVD)worldwide,is responsive to dietary interventions.However,studies investigating NK’s digestion,absorption,and mechanisms in mitigating AS remain limited.This study evaluated the effects of high-dose NK treatment(H-NK,900 FU/kg body weight)administered over six weeks in ApoE^(-/-) mice,which resulted in significant reductions in atherosclerotic lesions.In vitro digestion simulations showed that 25.8% of NK’s enzymatic activity was retained post-digestion,and thrombolysis assays demonstrated a thrombolytic efficacy of 30–40%at concentrations ≥5000μg/mL,regardless of clot age.Absorption experiments using a rat everted intestinal sac model revealed a small intestine absorption rate of 37.0%,with the absorbed peptides being predominantly hydrophobic,uncharged,and shorter than 10 amino acids.Proteomic analysis of mouse liver tissues identified that high-dose NK down-regulated PXDN(peroxidasin)and PNLIP(pancreatic lipase),proteins involved in promoting lipid oxidation,and intestinal lipid absorption.These proteomic changes enhanced lipid metabolism,reduced lipid peroxidation,and alleviated AS through the"Lipid and Atherosclerosis"pathway.Overall,this study provides a deeper understanding of NK’s biological activity and supports its potential as a novel dietary supplement for the management of CVD.
基金supported by the National Key R&D Program of China(2023YFF11103804)the earmarked fund for China Agriculture Research System of MOF and MARA(CARS-45).
文摘Immunosuppression is closely linked to intestinal barrier dysfunction and gut microbial imbalance.Our previous studies demonstrated that the Maillard reaction can effectively enhance the prebiotic function and antioxidant capacity of silver carp hydrolysates(SCH)in vitro,suggesting their potential immunomodulatory value.There-fore,this study investigated the prebiotic and immunomodulatory effects of Maillard reaction-modified silver carp hydrolysates(SCH-MRPs)in a cyclophosphamide-induced immunosuppression model.SCH-MRPs signifi-cantly improved both humoral and mucosal immunity by increasing serum immunoglobulins,normalizing colonic cytokine balance,and re-establishing CD4^(+)/CD8^(+)T-cell homeostasis.They also improved colon index,body weight,and colonic antioxidant capacity.Mechanistically,SCH-MRPs reactivated TLR4/NF-κB signaling,enhancing immune responsiveness,and reinforced intestinal barrier integrity through the upregulation of zonula occludens-1(ZO-1),Occludin,Claudin-1,and Muc-2.Additionally,SCH-MRPs reshaped the gut microbiota composition toward a more beneficial profile,characterized by enrichment of short chain fatty acid(SCFA)-producing bacteria such as Bacteroidetes and a reduction in potentially harmful genera like Candida-tus_Saccharimonas.These microbial shifts were accompanied by increased total SCFA levels,particularly propi-onic acid and butyric acid,along with upregulation of SCFA receptor expression.Overall,this study provides scientific evidence supporting SCH-MRPs as promising peptide-based prebiotic candidates for modulating gutimmune homeostasis and advancing functional food development.
基金supported by the National Key R&D Program of China(2023YFF11103804)the earmarked fund for China Agriculture Research System of MOF and MARA(CARS-45)support from the National Institute of Food and Agriculture,U.S.Department of Agriculture,Hatch-Multistate Project 7006446.
文摘Silver carp(Hypophthalmichthys molitrix)is a low-cost,protein-rich freshwater fish with high nutritional value but remains underutilized in functional food applications.Our previous studies have demonstrated that silver carp hydrolysates(SCH)possess potential in the management of chronic diseases and that their sensory properties and antioxidant activities can be further enhanced through Maillard reaction.However,the prebiotic potential of Maillard reaction-modified SCH has been rarely explored.This study investigates the prebiotic potential of SCH-based Maillard reaction products(SCH-MRPs)using in vitro fermentation model combined with 16S rRNA sequencing and metabolomics.During the fermentation process,moderate Maillard reaction significantly promoted SCFA production(approximately 16.29%)(p<0.05),particularly acetic,propionic,and butyric acids,which are known to play key roles in maintaining intestinal health and immune function.These changes were associated with increased microbial diversity,as indicated by higher Shannon(41.44%)and Simpson(18.30%)indices,along with a 264.24%increase in the relative abundance of Bacteroides.Metabolomics analysis revealed differential metabolites in the SCH-MRPs group suggested potential involvement in regulating tryptophan metabolism and bile secretion pathways,including indole-3-carboxaldehyde,indolepropionate,and glycochenodeoxycholic acid 3-glucuronide.Correlation analysis showed significant positive correlation between Fusobacterium,Bacteroides,and unidentified_Clostridiales abundances with indoles and derivatives,suggesting a regulatory role in tryptophan metabolism.This study systematically explores the prebiotic potential of Maillard reaction-modified SCH conjugated with oligosaccharides.By integrating microbial community analysis and metabolomics,it reveals a dual effect of SCH-MRPs in enhancing gut microbiota composition and metabolic activity,offering a promising strategy for microbiome-targeted functional food development.
