Type 2 diabetes mellitus(T2DM)is a complex metabolic disease threatening human health.We investigated the effects of Tegillarca granosa polysaccharide(TGP)and determined its potential mechanisms in a mouse model of T2...Type 2 diabetes mellitus(T2DM)is a complex metabolic disease threatening human health.We investigated the effects of Tegillarca granosa polysaccharide(TGP)and determined its potential mechanisms in a mouse model of T2DM established through a high-fat diet and streptozotocin.TGP(5.1×10^(3) Da)was composed of mannose,glucosamine,rhamnose,glucuronic acid,galactosamine,glucose,galactose,xylose,and fucose.It could significantly alleviate weight loss,reduce fasting blood glucose levels,reverse dyslipidemia,reduce liver damage from oxidative stress,and improve insulin sensitivity.RT-PCR and Western blotting indicated that TGP could activate the phosphatidylinositol-3-kinase/protein kinase B signaling pathway to regulate disorders in glucolipid metabolism and improve insulin resistance.TGP increased the abundance of Allobaculum,Akkermansia,and Bifidobacterium,restored the microbiota abundance in the intestinal tracts of mice with T2DM,and promoted short-chain fatty acid production.This study provides new insights into the antidiabetic effects of TGP and highlights its potential as a natural hypoglycemic nutraceutical.展开更多
The present study reports the structural characteristics of 3 polysaccharide fractions(SPS-F1,SPS-F2 and SPS-F3)isolated and purified from squash.SPS-F1(molecular weight(Mw)=12.30 kDa)and SPS-F2(Mw=19.40 kDa)were like...The present study reports the structural characteristics of 3 polysaccharide fractions(SPS-F1,SPS-F2 and SPS-F3)isolated and purified from squash.SPS-F1(molecular weight(Mw)=12.30 kDa)and SPS-F2(Mw=19.40 kDa)were likely to contain HG and RG-I domain of pectic polysaccharide,respectively.SPS-F2(Mw=270.4 kDa)was mainly composed of rhamnose,galactose and arabinose.The treatment with SPS decreased body weight gain,glucose and TG levels in type 2 diabetes rats.Besides,25 differential metabolites were identified based on urinary metabolomics analysis,which are crucial to the anti-diabetic effect of SPS.The regulation of nicotinamide N-oxide,histamine,cis-aconitate,citrate,L-malic acid,3-(3-hydroxyphenyl)propanoic acid and N-acetyl-L-aspartic acid were mainly associated with energy metabolism,gut microbiota and inflammation.Study of surface plasmon resonance revealed the binding kinetics with galectin-3(Gal-3)and fibroblast growth factor 2(FGF2).The K_(D)values of SPS-F2 and SPS-F3 to Gal-3 were 4.97×10^(-3)and 1.48×10^(-3)mol/L,indicating a weak binding affinity.All 3 fractions showed moderate binding to FGF2 and the affinity was SPS-F3>SPS-F2>SPS-F1.Thus,the metabolomics and SPR approach were proved to be a promising tool in exploring the anti-diabetes effects of SPS and provided a deep understanding of the mechanisms.展开更多
In previous study,we got a purified ginger polysaccharide UGP1 and verified its significant antitumor activities on colon cancer HCT116 cells.In this article,we aimed to illustrate the underlying mechanism of UGP1 exe...In previous study,we got a purified ginger polysaccharide UGP1 and verified its significant antitumor activities on colon cancer HCT116 cells.In this article,we aimed to illustrate the underlying mechanism of UGP1 exerted antitumor activities on colon cancer by using in vitro cell models and in vivo animal models.The results demonstrated that UGP1 could induce S-phase cell cycle arrest,up-regulate the expression of Bax and p53,down-regulate the expression of Bcl-2,and activate the downstream protein caspase-9 and caspase-3,which was related to intrinsic apoptosis pathway on HCT116 cells.Moreover,UGP1 significantly stimulated RAW264.7 cell proliferation and secretion activity.Similarly,UGP1 inhibited tumor proliferation on tumor-bearing mice,increased the expression of p53 and the ratio of Bax/Bcl-2,enhanced the secretion of pro-inflammatory cytokines TNF-α,IL-2,IL-6 and decreased the secretion of pro-tumor cytokines TGF-βand b FGF in serum.In conclusion,it indicated that the UGP 1 could sup press human colon cancer growth by inducing apoptosis via the regulation of p53,caspase-3,and Bax/Bcl-2 ratio-dependent pathway and regulating immune system activity.Thi s investigation provided basic theoretical mechanism of ginger polysaccharideexerted antitumor activities,and contributed to develop a possible functional food or adjuvant agent for prevention or treatment of colon cancer.展开更多
Iron deficiency anemia(IDA)is a common nutritional problem, but traditional iron supplements cause many adverse reactions. Thus, the development of a novel iron supplement might be significant for the treatment of IDA...Iron deficiency anemia(IDA)is a common nutritional problem, but traditional iron supplements cause many adverse reactions. Thus, the development of a novel iron supplement might be significant for the treatment of IDA. This study aimed to study the transport mechanism of Flammulina velutipes polysaccharide-iron complex(FVP1-Fe(Ⅲ))in Caco-2 cells and the therapeutic effect on IDA rats, as well as the influence on gut microbiota in vivo. These results showed that in vitro, the uptake of FVP1-Fe(Ⅲ)was mediated by sodium-dependent glucose transporter-1(SGLT1)and facilitated glucose transporter-2(GLUT2)and GLUT2 played a dominant function. The multidrug resistance-associated protein-2(MRP-2)was involved in the efflux of FVP1-Fe(Ⅲ)across the Caco-2 cells. In vivo, FVP1-Fe(Ⅲ)had a better restorative effect on blood parameters and iron status indicators in rats with IDA as compared with FeSO_4 and exerted this effect by downregulating the expression of hepcidin. FVP1-Fe(Ⅲ)could also regulate gut microbiota dysbiosis in iron deficiency rats by returning the relative abundance of gut microbiota to the normal level. Besides, as a dietary factor, vitamin C(vit C)could enhance the therapeutic effect of FVP1-Fe(Ⅲ). These present findings showed that FVP1-Fe(Ⅲ)could be exploited as a novel iron supplement to treat IDA.展开更多
Polysaccharides are widely present in herbs with multiple activities,especially immunity regulation and metabolic benefits for metabolic disorders.However,the underlying mechanisms are not well under-stood.Functional ...Polysaccharides are widely present in herbs with multiple activities,especially immunity regulation and metabolic benefits for metabolic disorders.However,the underlying mechanisms are not well under-stood.Functional metabolomics is increasingly used to investigate systemic effects on the host by iden-tifying metabolites with particular functions.This study explores the mechanisms underlying the metabolic benefits of Astragalus polysaccharides(APS)by adopting a functional metabolomics strategy.The effects of APS were determined in eight-week high-fat diet(HFD)-fed obese mice.Then,gas chromatography–time-of-flight mass spectrometry(GC–TOFMS)-based untargeted metabolomics was performed for an analysis of serum and liver tissues,and liquid chromatography–tandem mass spectrom-etry(LC–MS/MS)-based targeted metabolomics was performed.The potential functions of the metabo-lites were tested with in vitro and in vivo models of metabolic disorders.Our results first confirmed the metabolic benefits of APS in obese mice.Then,metabolomics analysis revealed that APS supplemen-tation reversed the HFD-induced metabolic changes,and identified 2-hydroxybutyric acid(2-HB)as a potential functional metabolite for APS activity that was significantly decreased by a HFD and reversed by APS.Further study indicated that 2-HB inhibited oleic acid(OA)-induced triglyceride(TG)accumula-tion.It was also found to stimulate the expression of proteins in lipid degradation in hepatocytes and TG lipolysis in 3T3-L1 cells.Moreover,it was found to reduce serum TG and regulate the proteins involved in lipid degradation in high-fat and high-sucrose(HFHS)-fed mice.In conclusion,our study demonstrates that the metabolic benefits of APS are at least partially due to 2-HB generation,which modulated lipid metabolism both in vitro and in vivo.Our results also highlight that functional metabolomics is practical for investigating the mechanism underlying the systemic benefits of plant polysaccharides.展开更多
Senventy nine advanced cancer patients in a clinical trial were treated with LAK/IL-2 combining with Lycium Barbarum polysaccharides (LBP). Initial results of the treatment from 75 evaluable Patients indicated that ob...Senventy nine advanced cancer patients in a clinical trial were treated with LAK/IL-2 combining with Lycium Barbarum polysaccharides (LBP). Initial results of the treatment from 75 evaluable Patients indicated that objective ragression of cancer was achieved in Patients with malignant melanoma, renal cell carcinoma, colorectal carcinoma, lung caneer, nasophacyngeal carcinoma,malignant hydrothorax. The response rate of patients treated with LAK/IL-2 plus LBP was 40.9% while that of patients treated with LAK/IL-2 was 16.1% (P<0.05).The mean remission duration in Patients treated with LAK/IL-2 Plus LBP also lasted significantly longer.LAK/IL-2 plus LBP treatment led to more marked increase in NK and LAK cell activity than LAK/IL-2without LBP. The results indicated that LBP can be used as an adjuvant in the biotherapy of cancer.展开更多
Type 2 diabetes mellitus(T2DM)is a metabolic disease caused by a glycolipid metabolism disorder and isletβ-cell dysfunction.SCP-80-I is a biologically active water-soluble polysaccharide isolated from sweet corncob,a...Type 2 diabetes mellitus(T2DM)is a metabolic disease caused by a glycolipid metabolism disorder and isletβ-cell dysfunction.SCP-80-I is a biologically active water-soluble polysaccharide isolated from sweet corncob,an agricultural byproduct.The hypoglycemic effects of SCP-80-I on T2DM mice and its mechanisms were investigated in this study.SCP-80-I was found to significantly reduce blood glucose and lipid deposition levels in T2DM mice,as well as decrease serum leptin and increase adiponectin secretion.Interestingly,real time-polymerase chain reaction(RT-PCR)and Western blotting results revealed that SCP-80-I could regulate the expression of several glycolipid metabolisms and insulin secretion genes and proteins,including 5'-AMP-activated protein kinase(AMPK),carnitine palmitoyltransferase I(CPTI),and acetyl coenzyme A carboxylase(ACC)in the liver and AMPK,sirtuin1(Sirtl),peroxisome proliferator-activated receptorycoactivator-1(PGC-1α),and uncoupling protein 2(UCP2)in the pancreas.To have a hypoglycemic effect,SCP-80-1 regulated glycolipid metabolism and islet cell function in the liver by regulating the AMPK/AC C/CPT1 signaling pathway and the AMPK/Sirt1/PGC-1αand AMPK/Sirtl/UCP2 signaling pathways.These findings improve our understanding of polysaccharides derived from sweet corncob and the use of SCP-80-I in the production of hypoglycemic foods.展开更多
基金funded by the National Key Research and Development Program of China(2020YFD0900902)Zhejiang Province Public Welfare Technology Application Research Project(LGJ21C20001)Zhejiang Provincial Key Research and Development Project of China(2019C02076 and 2019C02075)。
文摘Type 2 diabetes mellitus(T2DM)is a complex metabolic disease threatening human health.We investigated the effects of Tegillarca granosa polysaccharide(TGP)and determined its potential mechanisms in a mouse model of T2DM established through a high-fat diet and streptozotocin.TGP(5.1×10^(3) Da)was composed of mannose,glucosamine,rhamnose,glucuronic acid,galactosamine,glucose,galactose,xylose,and fucose.It could significantly alleviate weight loss,reduce fasting blood glucose levels,reverse dyslipidemia,reduce liver damage from oxidative stress,and improve insulin sensitivity.RT-PCR and Western blotting indicated that TGP could activate the phosphatidylinositol-3-kinase/protein kinase B signaling pathway to regulate disorders in glucolipid metabolism and improve insulin resistance.TGP increased the abundance of Allobaculum,Akkermansia,and Bifidobacterium,restored the microbiota abundance in the intestinal tracts of mice with T2DM,and promoted short-chain fatty acid production.This study provides new insights into the antidiabetic effects of TGP and highlights its potential as a natural hypoglycemic nutraceutical.
基金supported by the National Natural Science Foundation of China(32122069 and 31972191)the Beijing Outstanding Young Scientist Program(BJJWZYJH01201910011025)funded by National Institutes of Health Grants DK111958 and AG062344 to R.J.L.
文摘The present study reports the structural characteristics of 3 polysaccharide fractions(SPS-F1,SPS-F2 and SPS-F3)isolated and purified from squash.SPS-F1(molecular weight(Mw)=12.30 kDa)and SPS-F2(Mw=19.40 kDa)were likely to contain HG and RG-I domain of pectic polysaccharide,respectively.SPS-F2(Mw=270.4 kDa)was mainly composed of rhamnose,galactose and arabinose.The treatment with SPS decreased body weight gain,glucose and TG levels in type 2 diabetes rats.Besides,25 differential metabolites were identified based on urinary metabolomics analysis,which are crucial to the anti-diabetic effect of SPS.The regulation of nicotinamide N-oxide,histamine,cis-aconitate,citrate,L-malic acid,3-(3-hydroxyphenyl)propanoic acid and N-acetyl-L-aspartic acid were mainly associated with energy metabolism,gut microbiota and inflammation.Study of surface plasmon resonance revealed the binding kinetics with galectin-3(Gal-3)and fibroblast growth factor 2(FGF2).The K_(D)values of SPS-F2 and SPS-F3 to Gal-3 were 4.97×10^(-3)and 1.48×10^(-3)mol/L,indicating a weak binding affinity.All 3 fractions showed moderate binding to FGF2 and the affinity was SPS-F3>SPS-F2>SPS-F1.Thus,the metabolomics and SPR approach were proved to be a promising tool in exploring the anti-diabetes effects of SPS and provided a deep understanding of the mechanisms.
基金supported by the National Key Research and Development Project“Modern food processing and food storage and transportation technology and equipment”(2017YFD0400203)。
文摘In previous study,we got a purified ginger polysaccharide UGP1 and verified its significant antitumor activities on colon cancer HCT116 cells.In this article,we aimed to illustrate the underlying mechanism of UGP1 exerted antitumor activities on colon cancer by using in vitro cell models and in vivo animal models.The results demonstrated that UGP1 could induce S-phase cell cycle arrest,up-regulate the expression of Bax and p53,down-regulate the expression of Bcl-2,and activate the downstream protein caspase-9 and caspase-3,which was related to intrinsic apoptosis pathway on HCT116 cells.Moreover,UGP1 significantly stimulated RAW264.7 cell proliferation and secretion activity.Similarly,UGP1 inhibited tumor proliferation on tumor-bearing mice,increased the expression of p53 and the ratio of Bax/Bcl-2,enhanced the secretion of pro-inflammatory cytokines TNF-α,IL-2,IL-6 and decreased the secretion of pro-tumor cytokines TGF-βand b FGF in serum.In conclusion,it indicated that the UGP 1 could sup press human colon cancer growth by inducing apoptosis via the regulation of p53,caspase-3,and Bax/Bcl-2 ratio-dependent pathway and regulating immune system activity.Thi s investigation provided basic theoretical mechanism of ginger polysaccharideexerted antitumor activities,and contributed to develop a possible functional food or adjuvant agent for prevention or treatment of colon cancer.
基金supported by the State key research and development plan “Modern food processing and food storage and transportation technology and equipment” (2017YFD0400203)。
文摘Iron deficiency anemia(IDA)is a common nutritional problem, but traditional iron supplements cause many adverse reactions. Thus, the development of a novel iron supplement might be significant for the treatment of IDA. This study aimed to study the transport mechanism of Flammulina velutipes polysaccharide-iron complex(FVP1-Fe(Ⅲ))in Caco-2 cells and the therapeutic effect on IDA rats, as well as the influence on gut microbiota in vivo. These results showed that in vitro, the uptake of FVP1-Fe(Ⅲ)was mediated by sodium-dependent glucose transporter-1(SGLT1)and facilitated glucose transporter-2(GLUT2)and GLUT2 played a dominant function. The multidrug resistance-associated protein-2(MRP-2)was involved in the efflux of FVP1-Fe(Ⅲ)across the Caco-2 cells. In vivo, FVP1-Fe(Ⅲ)had a better restorative effect on blood parameters and iron status indicators in rats with IDA as compared with FeSO_4 and exerted this effect by downregulating the expression of hepcidin. FVP1-Fe(Ⅲ)could also regulate gut microbiota dysbiosis in iron deficiency rats by returning the relative abundance of gut microbiota to the normal level. Besides, as a dietary factor, vitamin C(vit C)could enhance the therapeutic effect of FVP1-Fe(Ⅲ). These present findings showed that FVP1-Fe(Ⅲ)could be exploited as a novel iron supplement to treat IDA.
基金funded by the National Natural Science Foundation of China (81673662 and 81873059)the Program for Professor of Special Appointment (Eastern Scholar)&Shuguang Scholar (16SG36) at the Shanghai Institutions of Higher Learning from Shanghai Municipal Education
文摘Polysaccharides are widely present in herbs with multiple activities,especially immunity regulation and metabolic benefits for metabolic disorders.However,the underlying mechanisms are not well under-stood.Functional metabolomics is increasingly used to investigate systemic effects on the host by iden-tifying metabolites with particular functions.This study explores the mechanisms underlying the metabolic benefits of Astragalus polysaccharides(APS)by adopting a functional metabolomics strategy.The effects of APS were determined in eight-week high-fat diet(HFD)-fed obese mice.Then,gas chromatography–time-of-flight mass spectrometry(GC–TOFMS)-based untargeted metabolomics was performed for an analysis of serum and liver tissues,and liquid chromatography–tandem mass spectrom-etry(LC–MS/MS)-based targeted metabolomics was performed.The potential functions of the metabo-lites were tested with in vitro and in vivo models of metabolic disorders.Our results first confirmed the metabolic benefits of APS in obese mice.Then,metabolomics analysis revealed that APS supplemen-tation reversed the HFD-induced metabolic changes,and identified 2-hydroxybutyric acid(2-HB)as a potential functional metabolite for APS activity that was significantly decreased by a HFD and reversed by APS.Further study indicated that 2-HB inhibited oleic acid(OA)-induced triglyceride(TG)accumula-tion.It was also found to stimulate the expression of proteins in lipid degradation in hepatocytes and TG lipolysis in 3T3-L1 cells.Moreover,it was found to reduce serum TG and regulate the proteins involved in lipid degradation in high-fat and high-sucrose(HFHS)-fed mice.In conclusion,our study demonstrates that the metabolic benefits of APS are at least partially due to 2-HB generation,which modulated lipid metabolism both in vitro and in vivo.Our results also highlight that functional metabolomics is practical for investigating the mechanism underlying the systemic benefits of plant polysaccharides.
文摘Senventy nine advanced cancer patients in a clinical trial were treated with LAK/IL-2 combining with Lycium Barbarum polysaccharides (LBP). Initial results of the treatment from 75 evaluable Patients indicated that objective ragression of cancer was achieved in Patients with malignant melanoma, renal cell carcinoma, colorectal carcinoma, lung caneer, nasophacyngeal carcinoma,malignant hydrothorax. The response rate of patients treated with LAK/IL-2 plus LBP was 40.9% while that of patients treated with LAK/IL-2 was 16.1% (P<0.05).The mean remission duration in Patients treated with LAK/IL-2 Plus LBP also lasted significantly longer.LAK/IL-2 plus LBP treatment led to more marked increase in NK and LAK cell activity than LAK/IL-2without LBP. The results indicated that LBP can be used as an adjuvant in the biotherapy of cancer.
基金financially supported by the Doctoral Scientific Research Start-up Foundation of the Harbin University of Commerce (2019DS098)the Young Innovation Talents Project from the Harbin University of Commerce (2019CX31)the Graduate Innovation Fund from the Harbin University of Commerce (YJSCX2019–615HSD)。
文摘Type 2 diabetes mellitus(T2DM)is a metabolic disease caused by a glycolipid metabolism disorder and isletβ-cell dysfunction.SCP-80-I is a biologically active water-soluble polysaccharide isolated from sweet corncob,an agricultural byproduct.The hypoglycemic effects of SCP-80-I on T2DM mice and its mechanisms were investigated in this study.SCP-80-I was found to significantly reduce blood glucose and lipid deposition levels in T2DM mice,as well as decrease serum leptin and increase adiponectin secretion.Interestingly,real time-polymerase chain reaction(RT-PCR)and Western blotting results revealed that SCP-80-I could regulate the expression of several glycolipid metabolisms and insulin secretion genes and proteins,including 5'-AMP-activated protein kinase(AMPK),carnitine palmitoyltransferase I(CPTI),and acetyl coenzyme A carboxylase(ACC)in the liver and AMPK,sirtuin1(Sirtl),peroxisome proliferator-activated receptorycoactivator-1(PGC-1α),and uncoupling protein 2(UCP2)in the pancreas.To have a hypoglycemic effect,SCP-80-1 regulated glycolipid metabolism and islet cell function in the liver by regulating the AMPK/AC C/CPT1 signaling pathway and the AMPK/Sirt1/PGC-1αand AMPK/Sirtl/UCP2 signaling pathways.These findings improve our understanding of polysaccharides derived from sweet corncob and the use of SCP-80-I in the production of hypoglycemic foods.
