A new water-soluble heteropolysaccharide with a molecular weight of 15 k Da was isolated from the fruiting bodies of Boletus reticulatus Schaeff.Structural characterization results revealed that B.reticulatus Schaeff ...A new water-soluble heteropolysaccharide with a molecular weight of 15 k Da was isolated from the fruiting bodies of Boletus reticulatus Schaeff.Structural characterization results revealed that B.reticulatus Schaeff polysaccharide(BRS-X)had a backbone of 1,6-linkedα-D-galactose and 1,2,6-linkedα-D-galactose which branches were mainly composed of a terminal 4-linkedβ-D-glucose and the ratio of D-galactose and D-glucose was 5:1.Bioactivity assays indicated that BRS-X displayed a strong proliferative activity in T cells and B cells and promoted the secretion of immunoglobulin G(Ig G),Ig E,Ig D and Ig M.In addition,BRS-X could facilitate the proliferation and phagocytosis of RAW264.7 cells and could significantly inhibit the growth of tumors in S180-bearing mice.The results of transcriptome sequencing analysis illustrated that total 46 genes enriched in MAPK and total 34 genes enriched in PI3 K/Akt signaling pathways in BRS-X group.The protein VEGF and VEGFR expression were significantly reduced under the treatment with BRS-X.These findings provide a scientific basis for the edible and medicinal value of BRS-X.展开更多
Bamboo shavings, the outer or intermediate layer of bamboo stems, are the bulk of by-products produced in bamboo processing. In this study we investigated the isolation, chemical characterization, and immunostimulator...Bamboo shavings, the outer or intermediate layer of bamboo stems, are the bulk of by-products produced in bamboo processing. In this study we investigated the isolation, chemical characterization, and immunostimulatory activity in vitro of the hemicelluloses from bamboo shavings. Shavings were first pretreated by steam explosion. The optimal pretreatment was found to be steam explosion at 2.2 MPa for 1 min. Following this pretreatment, the yield of hemicelluloses reached（2.05±0.22）%（based on the dry dewaxed raw materials）, which was 5.7-fold higher than that of untreated samples. Bamboo-shavings hemicellulose（BSH） was then prepared by hot water extraction and ethanol precipitation from the steam-exploded shavings. Purification of BSH by anion-exchange chromatography of diethylaminoethanol（DEAE）-sepharose Fast Flow resulted in a neutral fraction（BSH-1, purity of 95.3%, yield of 1.06%） and an acidic fraction（BSH-2, purity of 92.5%, yield of 0.79%）. The weight-average molecular weights（Mw） of BSH-1 and BSH-2 were 12 800 and 11 300 g/mol, respectively. Chemical and structural analyses by Fourier transform infrared spectroscopy（FT-IR）, 1D（^1H and ^13C） and 2D（heteronuclear single quantum correlation（HSQC）） nuclear magnetic resonance（NMR） spectra revealed that BSH-1 was O-acetylated-arabinoxylan and BSH-2 was O-acetylated-（4-Omethylglucurono）-arabinoxylan. BSH-1 had a higher content of acetyl groups than BSH-2. For the immunomodulatory activity in vitro, BSH and BSH-2 significantly stimulated mouse splenocyte proliferation while BSH-1 had no effect; BSH, BSH-1, and BSH-2 markedly enhanced the phagocytosis activity and nitric oxide production of the murine macrophage RAW264.7 in a dose-dependent manner. Our results suggest that the water-extractable hemicelluloses from steam-exploded bamboo shavings are naturally acetylated and have immunostimulatory activity.展开更多
To fully understand the proliferation of splenocyte in vitro of natto ingredients,two kinds of polysaccharideprotein complexes,named as NPPC-1-b and NPPC-2-a,were extracted and purified from natto by DEAE-52 cellulose...To fully understand the proliferation of splenocyte in vitro of natto ingredients,two kinds of polysaccharideprotein complexes,named as NPPC-1-b and NPPC-2-a,were extracted and purified from natto by DEAE-52 cellulose ionexchange chromatography and Sephadex G-100 gel filtration chromatography.Their molecular weights were determined by performance gel permeation chromatography to be approximately 26.93 and 357.60 k D for NPPC-1-b and NPPC-2-a,respectively.The two complexes were further characterized by FT-IR,UV-visible spectrophotometry,monosaccharide and amino acid composition analysis.The results showed that NPPC-1-b contained an O-glycopeptide bond,while NPPC-2-a contained an N-glycopeptide bond.NPPC-1-b was mainly composed of mannose(Man),rhamnose(Rha)and arabinose(Ara),with the contents of 67.45%,25.67%and 2.44%,respectively.However,NPPC-2-a was mainly composed of glucose(Glc),mannose(Man),arabinose(Ara),xylose(Xyl)and galactose(Gal),accounting for 36.64%,21.71%,10.35%,9.00%and 5.17%,respectively.Seventeen amino acids were identified in both complexes.NPPC-1-b was mainly composed of glutamic(Glu),proline(Pro),lysine(Lys)and arginine(Arg)with contents of 0.971%,0.791%,0.708%and 0.603%,while NPPC-2-a was mainly composed of Glu,Pro and aspartic(Asp)acid with contents of 0.903%,0.689%and 0.504%.Besides,preliminary in vitro tests showed that NPPC-1-b(100-200μg/m L)and NPPC-2-a(12.5-200μg/m L)exhibited significantly higher immunomodulatory activities against the proliferation of lymphocytes(P 0.05),and the effect of 100μg/m L NPPC-2-a was the best.In respect of cytokines expression,NPPC-1-b and NPPC-2-a significantly enhanced the expression of interleukin-2(IL-2)and interferon-γ(INF-γ),and 50μg/m L NPPC-1-b showed a strong effect on IL-2 secretion,200μg/m L NPPC-2-a exhibited a strong effect on INF-γsecretion.These results suggest that NPPC-1-b and NPPC-2-a can effectively increase immunomodulatory activity.展开更多
Microbial fermentation improves the physicochemical properties,structure,and biological activity of plant polysaccharides,and is an environmentally safer processing method.In this study,Cyclocarya paliurus(C.paliurus)...Microbial fermentation improves the physicochemical properties,structure,and biological activity of plant polysaccharides,and is an environmentally safer processing method.In this study,Cyclocarya paliurus(C.paliurus)polysaccharide(CP)was obtained through fermentation with Penicillium EF-2.Physicochemical characterisation and macrophage RAW264.7 revealed that fermentation altered the monosaccharide composition and structure of fermented C.paliurus polysaccharide(FCP),enhancing its thermal stability,apparent viscosity,and in vitro immune activity.Metabolomics analysis further indicated that the metabolic pathway of cellulose was activated,facilitating the dissolution of cellulose and hemicellulose in the fermentation broth through the degradation of cellulose in the cell wall of C.paliurus.This process increased polysaccharide production and modified the polysaccharide structure.This study provides a theoretical foundation for the development and utilisation of microbial fermentation-modified polysaccharides and CP.展开更多
In order to better the structure and immunomodulatory activity relationships of Dendrobium officinale polysaccharides,this study partially degraded DOP with a molecular weight of 264 kDa using endo-β-1,4-mannanase.De...In order to better the structure and immunomodulatory activity relationships of Dendrobium officinale polysaccharides,this study partially degraded DOP with a molecular weight of 264 kDa using endo-β-1,4-mannanase.Dendrobium offinale polysaccharides(DOP)and two degraded fractions(DOP-30:51 kDa and DOP-60:28 kDa)were structurally characterized and evaluated for in vitro immunomodulatory activity.Structural analysis indicated that enzymatic hydrolysis of DOP can effectively produce low molecular weight polysaccharides with similar structures but slightly different chemical compositions.The backbone structures of DOPs were all consisted of→4)-β-D-Manp-(1→,→4)-β-D-Glcp-(1→,→4)-2-O-acetyl-β-D-Manp-(1→and→4)-3-O-acetyl-β-D-Manp-(1→.All DOPs enhanced the proliferation and phagocytosis of RAW264.7 macrophages,promoted the secretion of immune effector molecules,and facilitated the polarized of macrophages to the M1 phenotype,as well as the expression of Toll-like receptor 4(TLR4)in vitro.Among them,DOP-60 showed relatively strong immunomodulatory activity.Correlation analysis further indicated that molecular weight(Mw)was most closely correlated with macrophage activation by DOP,suggesting that low molecular weight DOP has a greater potential to activate macrophages.展开更多
Glycoprotein complexes,a kind of structural biomolecules,are characterized by extensive functions,such as immunomodulatory and anti-inflammatory activities.Glycosylation of protein has an important impact on conformat...Glycoprotein complexes,a kind of structural biomolecules,are characterized by extensive functions,such as immunomodulatory and anti-inflammatory activities.Glycosylation of protein has an important impact on conformational stability and active function of glycoprotein complex.Clarifying the structure of glycoprotein complex is the basis for further exploring its biological activities,and the release of sugar chains is one of the key points in the analysis of glycoprotein structures.Glycoprotein complex can affect the expression of immune-related proteins and factors by activating cell surface receptors,regulating intracellular immune signal transduction,and ultimately play an immunomodulatory role in the body.Meanwhile,the chemical structure and advanced structure of glycoprotein complex can significantly affect the immunomodulatory activity.this review focuses on chemical and advanced structural information of glycoprotein,the regulation mechanism of immunomodulation and the structure-activity relationship,which aims to provide a theoretical basis for the basic research on the immunomodulatory activity of food-derived glycoproteins and the development of related functional products.展开更多
Objective:To investigate the immunomodulatory activity of polysaccharides from the roots of Brassica rapa.Methods:The crude polysaccharide from roots of B.rapa(BRP)was extracted and purified to further investigate the...Objective:To investigate the immunomodulatory activity of polysaccharides from the roots of Brassica rapa.Methods:The crude polysaccharide from roots of B.rapa(BRP)was extracted and purified to further investigate the active fraction of BRT for inducing macrophage phagocytosis.Results:Effects on RAW264.7 cells demonstrated that BRP behaved better phagocytic capacity and had potent immunomodulatory activity,including increasing production of nitric oxide(NO),tumor necrosis factor a(TNFa)and upregulating mRNA levels of inducible NO synthase(iNOS)and TNFa.Furthermore,modulation of macrophage by BRP was indicated to be mediated via the activation of Akt and nuclear factor-kappa B(NF-κB).Conclusion:The beneficial effects of BRP could be used as an immunotherapeutic adjuvant in treatment of inflammatory diseases.展开更多
In order to reveal the intrinsic nature of the reduction or disappearance of biological activity in the processing and preparation of polysaccharides,and realize the effective control of highly active polysaccharides,...In order to reveal the intrinsic nature of the reduction or disappearance of biological activity in the processing and preparation of polysaccharides,and realize the effective control of highly active polysaccharides,the correlation between conformation and immunomodulatory activity of lentinan under different subcritical water temperatures was investigated.The results showed that,compared with the lentinan extracted by hot water(HW-L),with the increase of temperature(100–160℃),the molecular weight of lentinans decreased(5.041×10^(5)–1.754×10^(6) g/mol)and the rigidity of the chain weakened.The chains gradually loosened and a rigid-flexible transition occurred.At 160°C,the conformation of lentinan completely changed from triple helix to random coil.In-vitro cell experiments showed that,lentinan at 120℃ could more efficiently promote the proliferation and phagocytosis of RAW264.7 cells,and significantly promote the secretion of NO,TNF-α,IL-6 and IL-1β,exhibiting stronger immunomodulatory activity.But the activity of lentinan decreased sharply at 150–160℃.These results suggest a significant correlation between polysaccharide chain conformation and immunomodulatory activity under different subcritical water temperature conditions.By adjusting the temperature of subcritical water,the chain conformation of polysaccharides can be controlled,resulting in more efficient extraction of highly active polysaccharides.展开更多
Stipes are the major waste from the processing of Lentinus edodes.To make full use of L.edodes stipes(LES),differ-ent fractions of LES polysaccharides(LESPs)were first obtained by water extraction and gradient ethanol...Stipes are the major waste from the processing of Lentinus edodes.To make full use of L.edodes stipes(LES),differ-ent fractions of LES polysaccharides(LESPs)were first obtained by water extraction and gradient ethanol precipitation.Afterwards,the LES residues were treated with an optimal combination of Aspergillus niger and Saccharomyces cerevisiae for the preparation of soluble/insoluble dietary fibers(LESS/LESI)using the response surface methodology and the Box-Behnken design.Subsequently,the in vitro immunomodulatory activity of LESPs and LESS,as well as the adsorption capacities of LESI were evaluated.The results showed that LESPs were neutral polysaccharides,mainly containing glucose.The optimal parameters for modifying the residues of LES were the followings:4%(w/w)A.niger,8%(w/w)S.cerevisiae,31℃,3 d,and a solid-liquid ratio of 1:12.5 in a yield of 14.73%/82.45%of LESS/LESI,respectively.The in vitro immunomodulatory activity assays revealed that LESPs and LESS had potent immunostimulatory activity to increase phagocytosis,acid phosphatase activity and nitric oxide production of RAW264.7 murine cell macrophages.The evaluation of adsorption capacities revealed that LESI owned stronger water holding capacity,oil holding capacity and water swelling capacity.This research could provide an effective way to fully utilize discarded L.edodes stipes with high added-value.展开更多
Levan is a fructose homopolymer obtained from both plants and microorganisms.Microbial levan is typically produced in a variety of molecular weights(MW).Previous studies have shown that different MW of levan exhibit d...Levan is a fructose homopolymer obtained from both plants and microorganisms.Microbial levan is typically produced in a variety of molecular weights(MW).Previous studies have shown that different MW of levan exhibit different biological activities.Though levan was reported for its immunomodulatory effect by increasing nitric oxide(NO)production in RAW264.7 macrophage cells,whether its MW can affect this activity remains unknown.In this study,the effect of different levan MW from Bacillus subtilis on its immunoregulatory properties was investigated.B.subtilis was cultivated using various cultivation parameters to obtain levan of different MW.Three weight average MW of levan,>8×10^(5) Da(M1),1.5×10^(4) Da(M2)and 3.7×10^(3) Da(M3),were selected to test for their effect on modulating NO levels in RAW264.7 cells.Our results showed that M2 increased NO production in a dose-dependent manner,and more effectively than that of M1 and M3.Consistent with these findings,M2 significantly stimulated inducible nitric oxide synthase(iNOS)and cyclooxygenase-2(COX2)protein expression,while less pronounced effects were observed in the cells treated with M1 and M3.Therefore,our results demonstrate that various MW of levan have varying effects on its immunoregulatory activities in RAW264.7 cells.Furthermore,our findings suggest that the size of levan should be taken into account when employing levan as one of the active ingredients in functional foods and immunomodulatory products.展开更多
Background:Lysozyme is a naturally occurring antimicrobial protein with known enzymatic and immunomodulatory properties.In addition to the well-characterized monomeric form,a dimeric form of lysozyme is clinically use...Background:Lysozyme is a naturally occurring antimicrobial protein with known enzymatic and immunomodulatory properties.In addition to the well-characterized monomeric form,a dimeric form of lysozyme is clinically used as an immunomodulatory drug.However,the biological activity of higher-order oligomers remains poorly understood,particularly in the context of innate immune signaling.Objective:This study aimed to develop a simplified method for lysozyme oligomerization and to characterize the resulting preparations with respect to their antimicrobial and immunomodulatory activity,particularly their ability to activate the nuclear factor kappa B signaling pathway.Methodology:Lysozyme hydrochloride was thermochemically modified using hydrogen peroxide at 90℃for 20 min,followed by catalase neutralization.Size-exclusion high-performance liquid chromatography was used to quantify oligomer content.Enzymatic activity against Gram-positive bacteria was assessed spectrophotometrically,while antibacterial activity against Gram-negative bacteria was evaluated by turbidimetric assay.Immunomodulatory properties were examined using THP1-Blue^(TM)NF-κB reporter cells.Results:The proposed method enabled efficient oligomerization without the need for pH adjustment or multistep procedures.Oligomer content increased proportionally with hydrogen peroxide concentration and was inversely correlated with enzymatic(muramidase)activity.All modified preparations exhibited approximately two-fold increased antibacterial activity against Gram-negative bacteria compared to native lysozyme.Notably,the oligomer-rich preparations induced significantly higher NF-κB activation in THP1-Blue^(TM)cells(up to three-fold compared to native lysozyme),suggesting enhanced immunomodulatory potential.Conclusions:Thermochemically generated lysozyme oligomers retain and even improve biological activity despite reduced enzymatic capacity.Their ability to activate innate immune signaling highlights their potential as dual-action bioactive agents with antimicrobial and immunostimulatory properties.展开更多
Chroogomphis rutilus is a kind of delicious edible fungus rich in bioactive components such as polysaccharides,and has high nutritional values.However,the researches on the structure-activity relationship of polysacch...Chroogomphis rutilus is a kind of delicious edible fungus rich in bioactive components such as polysaccharides,and has high nutritional values.However,the researches on the structure-activity relationship of polysaccharide components are still ambiguous.In this study,the C.rutilus water-extracted polysaccharide(CRWP)and alkali-extracted polysaccharide(CRAP)were obtained using deionized water and weak alkali solutions,respectively,and purified by dialysis,and the gut microbiota mediated immune regulatory activities were further studied.Structural analysis results showed that both CRWP and CRAP exhibited typical polysaccharide characteristics,showing the main chains ofβ-(1→6)-Manp andβ-(1→6)-Glcp linkedβ-(1→6)-Manp,respectively,with the molecular weights of 1.91×10^(7) Da and 2.19×10^(7) Da.In cyclophosphamide induced immune-injured mice,CRWP and CRAP effectively regulated the Lactobacillaceae/Lactobacillus mediated plant hormone signal trans-duction pathway and Akkermansiacae/Akkermansia mediated lysine degradation pathway,respectively.Besides,CRWP exhibited superior immunomodulatory effects on the proportions of CD19+B cells and CD3+T cells in peripheral blood compared with CRAP.These findings provide experimental data and theoretical basis for the development and application of C.rutilus polysaccharides in functional food fields.展开更多
This study investigates the efficacy of polysaccharides derived from Osmunda japonica Thunb in the context of immunoinflammation and elucidates its underlying mechanisms.The findings demonstrate that Osmunda japonica ...This study investigates the efficacy of polysaccharides derived from Osmunda japonica Thunb in the context of immunoinflammation and elucidates its underlying mechanisms.The findings demonstrate that Osmunda japonica Thunb polysaccharides(OP)significantly enhances microcirculation in vivo,facilitates immune regu-lation,and markedly promotes cell proliferation.Notably,the high-dose OP group exhibited a 45.18%inhibition rate on ear edema in mice,with a maximum vasodilatory effect of 16.72%.Additionally,after 24 h of OP stimulation of macrophages,the most pronounced promotion of activity was observed at 151.36%when the OP concentration reached 100μg/mL.OP also stimulates the secretion of nitric oxide(NO)and pro-inflammatory cytokines,including interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-α),prostaglandin E2(PGE2),and interleukin-1β(IL-1β),indicating its potent biological activity.Furthermore,OP promotes macrophage activation and NO release by activating the mitogen-activated protein kinase(MAPK)and nuclear factor-kappa B(NF-κB)signaling pathways,with particular emphasis on the NF-κB pathway,as well as c-Jun N-terminal kinase(JNK)and p38 MAPK within the MAPK pathway.These findings not only elucidate the mechanisms by which OP functions in the realm of immune inflammation but also provide a scientific foundation for the development of immune-regulating food products,thereby contributing to enhanced human health.展开更多
Mustard seeds is a traditional Chinese natural product of pharmaceutical and dietary origin,rich in polyphenols,flavonoids,and other active ingredients,exhibiting multiple bioactivities.In order to improve the yield,p...Mustard seeds is a traditional Chinese natural product of pharmaceutical and dietary origin,rich in polyphenols,flavonoids,and other active ingredients,exhibiting multiple bioactivities.In order to improve the yield,polyphenols from brown and white mustard seeds were extracted under better circumstances using Response Surface Methodology(RSM).Subsequently,components were assessed using LC-MS/MS.A total of 8 phenolic compounds and 3 flavonoid compounds were identified in brown mustard seeds extracts(BMSE),and 14 phenolic compounds and 4 flavonoid compounds were identified in white mustard seeds extracts(WMSE).Meanwhile,the biological activities of BMSE and WMSE were compared via in vitro free radical scavenging,hepatocyte oxidative injury protection,and macrophage immunoregulation models.The results showed that both BMSE and WMSE exhibited antioxidant activity and oxidative damage protection activity on HL-7702 cells,and BMSE was more effective.The viability of HL-7702 cells induced oxidative damage by hydrogen peroxide treated with BMSE and WMSE was increased by 36.7%and 32.8%,respectively.WMSE exhibited better in vitro immunomodulatory activities than BMSE,including proliferation promoting,phagocytosis,and NO release abilities on RAW264.7 cells.This study can contribute to the application of mustard seeds polyphenols in the field of functional foods,as well as provide a direction for the high-value utilization of mustard seeds.展开更多
Sepsis is characterized by a severe and life-threatening host immune response to polymicrobial infection accompanied by organ dysfunction.Studies on the therapeutic effect and mechanism of immunomodulatory drugs on th...Sepsis is characterized by a severe and life-threatening host immune response to polymicrobial infection accompanied by organ dysfunction.Studies on the therapeutic effect and mechanism of immunomodulatory drugs on the sepsis-induced hyperinflammatory or immunosuppression states of various immune cells remain limited.This study aimed to investigate the protective effects and underlying mechanism of artesunate(ART)on the splenic microenvironment of cecal ligation and puncture-induced sepsis model mice using single-cell RNA sequencing(scRNA-seq)and experimental validations.The scRNA-seq analysis revealed that ART inhibited the activation of pro-inflammatory macrophages recruited during sepsis.ART could restore neutrophils’chemotaxis and immune function in the septic spleen.It inhibited the activation of T regulatory cells but promoted the cytotoxic function of natural killer cells during sepsis.ART also promoted the differentiation and activity of splenic B cells in mice with sepsis.These results indicated that ART could alleviate the inflammatory and/or immunosuppressive states of various immune cells involved in sepsis to balance the immune homeostasis within the host.Overall,this study provided a comprehensive investigation of the regulatory effect of ART on the splenic microenvironment in sepsis,thus contributing to the application of ART as adjunctive therapy for the clinical treatment of sepsis.展开更多
Objective:To evaluate the cytotoxic,apoptotic,mutagenic and immunomodulatory activities of Kaempferia galanga Linn.(KG)extract and ethyl-p-methoxycinnamate(EPMC)in vitro.Methods:The present study investigated the cyto...Objective:To evaluate the cytotoxic,apoptotic,mutagenic and immunomodulatory activities of Kaempferia galanga Linn.(KG)extract and ethyl-p-methoxycinnamate(EPMC)in vitro.Methods:The present study investigated the cytotoxic[using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphe nyl-2-H-tetrazolium bromide test],apoptotic(using a mitochondrial membrane potential assay),mutagenic(using a micronucleus test)and immunomodulatory(using flow cytometry)activities of the ethanolic extract of KG and its bioactive component,EPMC,against two cholangiocarcinoma(CCA)cell lines,CL-6 and HuCCT1,and one normal human cell line,OUMS-36 T-1 F.Results:Both KG extract and EPMC exhibited moderate cytotoxic activity against both CCA cells.The cytotoxic activity was supported by their concentration-dependent induction of apoptosis.CL-6 was most sensitive(3–4 fold)and selective to 5-fluorouracil(5-FU),compared with KG extract and EPMC[median half inhibiting concentration(IC50)and selectivity index(SI)were 23.01 lg/mL and 17.32;78.41 lg/mL and 4.44;100.76 lg/mL and 2.20,respectively for 5-FU vs.KG extract vs.EPMC].HuCCT1 was relatively more sensitive and selective to 5-FU and EPMC than KG extract[median IC50 and SI were 66.03 lg/mL and6.04;60.90 lg/mL and 3.65;156.60 lg/mL and 2.23,respectively for 5-FU vs.EPMC vs.KG extract].EPMC produced relatively potent cytotoxic activity against polymorphonuclear cells(IC50=92.20 lg/mL).KG extract and EPMC exhibited concentration-dependent mutagenic activity,as well as inhibition of tumor necrosis factor-a and interleukin-6.Conclusion:Considering cytotoxic,apoptotic,immunomodulatory and mutagenic activities,further development of KG as a drug candidate is likely to focus on the oral pharmaceutical formulation of a standardized KG extract rather than isolated compounds.展开更多
Moderate steaming(4 h)enhances immunomodulatory activities of Polygonatum cyrtonema polysaccharides(PCPs);however,the bioactive fractions and their underlying mechanisms remain unclear.Herein,fractionation of steamed ...Moderate steaming(4 h)enhances immunomodulatory activities of Polygonatum cyrtonema polysaccharides(PCPs);however,the bioactive fractions and their underlying mechanisms remain unclear.Herein,fractionation of steamed rhizomes(PCP-4h)yielded five active fractions:two neutral polysaccharides(D1 and D2)and three acidic polysaccharides(D3-D5).Each fraction has a distinct molecular weight and monosaccharide composition.Acidic polysaccharides demonstrated superior immunomodulatory activities over neutral polysaccharides.RNA-seq revealed 3639,3668,and 3663 differentially expressed genes(DEGs)induced by D3-D5 that were enriched in TLR4-mediated MAPK(p-p38,p-ERK1/2 and p-JNK)and NF-κB(p-IκBαand p-p65)pathways.D3 exerted the strongest pathway effect,correlating with its superior bioactivity.Acidic polysaccharide fractions were identified as key bioactive drivers of PCP-4h immunomodulation via the TLR4-MAPK/NF-κB signaling pathway,facilitating the enhancement of bioactivity through optimized processing methods.展开更多
Russula vinosa Lindblad(R.vinosa Lindblad)is a nutrient-rich wild edible fungus,abundant in car-bohydrates.In this study,two polysaccharides(Russula polysaccharides extracted from 1%KOH(RP-1)and Russula polysaccharide...Russula vinosa Lindblad(R.vinosa Lindblad)is a nutrient-rich wild edible fungus,abundant in car-bohydrates.In this study,two polysaccharides(Russula polysaccharides extracted from 1%KOH(RP-1)and Russula polysaccharides extracted from 5%KOH(RP-5))were extracted from Russula fruit bodies using KOH-graded extraction technology.The molecular weights of RP-1 and RP-5 were 187000 and 97300 u,respectively.Their glycosyl compositions(galactose꞉glucose꞉xylose꞉mannose,i.e.,Gal꞉Glu꞉Xyl꞉Man)were 0.27:1.00:0.01:0.16 for RP-1 and 0.12:1.00:0.03:0.19 for RP-5.Nuclear magnetic resonance(NMR)analysis revealed that the main structural component of RP-1 was→3,6)-β-d-Glu p-(1→,with a→6)-β-d-Glu p-(1→residue linked at sites 1 and 6,and a→3)-β-d-Glu p-(1→residue linked at sites 3.The RP-5 shared this structure with an additional→4)-β-d-Man p-(1→residue attached to the→3)-β-d-Glu p-(1→.Phagocytosis assay demonstrated that RP-5,with a lower molecular weight,lower galactose content,and higher xylose and man-nose content,enhanced RAW 264.7 cell phagocytic activity by 121.04%,outperforming RP-1,which showed a 42.15%increase at the same concentration of 600𝜇g/mL.Furthermore,both RP-1 and RP-5 reduced the release of inflammatory factors and induced the nuclear translocation of the nuclear transcription factor-𝜅B(NF-𝜅B)pathway in RAW 264.7 cells.This study provided insights into the structural characteristics and immunomodulatory properties of Russula polysac-charides,offering potential for further applications in bioactive compound development.展开更多
Polysaccharides from Lentinula edodes mushrooms(LePS)are well-known for their immunomodulatory activities,which may have a functional connection with probiotic fermentation in the gut microbiota.This study was to eval...Polysaccharides from Lentinula edodes mushrooms(LePS)are well-known for their immunomodulatory activities,which may have a functional connection with probiotic fermentation in the gut microbiota.This study was to evaluate the bifidogenic properties and impact of Bifidobacterial fermentation on the LePS molecules and immunoactivities.Two LePS fractions,LePS-40(3.97×10^(7) Da)and LePS-80(1.43×10^(5) Da)with differences in molecular weight(MW)and chemical composition were isolated from the mushroom hot-water extract and fermented with a Bifidobacterium breve strain.The higher-MW fraction LePS-40 was more significantly consumed and utilized by the bacteria for growth and acetic acid production during the fermentation,due probably to its higher total carbohydrate content and glucose-abundant composition.The Bifidobacterial fermentation caused a notable MW reduction of both LePS fractions and,more interestingly,also led to a higher immunostimulatory activity in RAW 264.7 macrophage cells.Further assessment of the separated fractions by ultrafiltration of the fermentation liquid(digesta)suggested that the immunoactivity was mainly attributed to the partially degraded LePS instead of the small-molecule metabolite products derived from the Bifidobacterial fermentation.In summary,monosaccharide composition was a more significant determinant than MW on the bifidogenic properties of LePS and the immunomodulatory activities after fermentation.展开更多
In this study,casein hydrolysate was prepared by a two-step enzymatic method,and it was demonstrated that casein hydrolysate has good immunomodulatory activity in vitro and in vivo by cell and animal experiments.The c...In this study,casein hydrolysate was prepared by a two-step enzymatic method,and it was demonstrated that casein hydrolysate has good immunomodulatory activity in vitro and in vivo by cell and animal experiments.The casein hydrolysate prepared by two-step enzymatic method was characterized by high hydrolysis,of which 62.70%had molecular weight less than 1000 Da.Interestingly,the casein hydrolysate prepared by two-step enzymatic hydrolysis could activate macrophages and promote the phagocytosis of RAW 264.7 cells and the production of inflammatory factors.Additionally,the two-step enzymatic preparation of casein hydrolysate restored T-lymphocyte proliferation and natural killer cell activity and promoted the production of immunoglobulins and serum cytokines(IL-6,IL-1βand TNF-α)in immunocompromised treated mice.This study provides new ideas for developing novel functional foods or nutraceuticals.展开更多
基金supported by the Open Project Program of Irradiation Preservation Technology Key Laboratory of Sichuan Province,Sichuan Institute of Atomic Energy(FZBC2020009)the Open Research Fund Program of Departmental and Municipal Co-construction of Crops Genetic Improvement of Hill Land Key Laboratory of Sichuan Province(2021CGIHL02)+2 种基金Science and Technology Support Project of Nanchong Science and Technology Bureau of Sichuan Province(20YFZJ0053 and 20YFZJ0054)the Sericulture Innovation Team of Sichuan Province(SCCXTD-2021-17)Laboratory of Sichuan Province(2021CGIHL02)。
文摘A new water-soluble heteropolysaccharide with a molecular weight of 15 k Da was isolated from the fruiting bodies of Boletus reticulatus Schaeff.Structural characterization results revealed that B.reticulatus Schaeff polysaccharide(BRS-X)had a backbone of 1,6-linkedα-D-galactose and 1,2,6-linkedα-D-galactose which branches were mainly composed of a terminal 4-linkedβ-D-glucose and the ratio of D-galactose and D-glucose was 5:1.Bioactivity assays indicated that BRS-X displayed a strong proliferative activity in T cells and B cells and promoted the secretion of immunoglobulin G(Ig G),Ig E,Ig D and Ig M.In addition,BRS-X could facilitate the proliferation and phagocytosis of RAW264.7 cells and could significantly inhibit the growth of tumors in S180-bearing mice.The results of transcriptome sequencing analysis illustrated that total 46 genes enriched in MAPK and total 34 genes enriched in PI3 K/Akt signaling pathways in BRS-X group.The protein VEGF and VEGFR expression were significantly reduced under the treatment with BRS-X.These findings provide a scientific basis for the edible and medicinal value of BRS-X.
基金Project supported by the National Key Technology R&D Program of China(No.2012BAK01B03)
文摘Bamboo shavings, the outer or intermediate layer of bamboo stems, are the bulk of by-products produced in bamboo processing. In this study we investigated the isolation, chemical characterization, and immunostimulatory activity in vitro of the hemicelluloses from bamboo shavings. Shavings were first pretreated by steam explosion. The optimal pretreatment was found to be steam explosion at 2.2 MPa for 1 min. Following this pretreatment, the yield of hemicelluloses reached（2.05±0.22）%（based on the dry dewaxed raw materials）, which was 5.7-fold higher than that of untreated samples. Bamboo-shavings hemicellulose（BSH） was then prepared by hot water extraction and ethanol precipitation from the steam-exploded shavings. Purification of BSH by anion-exchange chromatography of diethylaminoethanol（DEAE）-sepharose Fast Flow resulted in a neutral fraction（BSH-1, purity of 95.3%, yield of 1.06%） and an acidic fraction（BSH-2, purity of 92.5%, yield of 0.79%）. The weight-average molecular weights（Mw） of BSH-1 and BSH-2 were 12 800 and 11 300 g/mol, respectively. Chemical and structural analyses by Fourier transform infrared spectroscopy（FT-IR）, 1D（^1H and ^13C） and 2D（heteronuclear single quantum correlation（HSQC）） nuclear magnetic resonance（NMR） spectra revealed that BSH-1 was O-acetylated-arabinoxylan and BSH-2 was O-acetylated-（4-Omethylglucurono）-arabinoxylan. BSH-1 had a higher content of acetyl groups than BSH-2. For the immunomodulatory activity in vitro, BSH and BSH-2 significantly stimulated mouse splenocyte proliferation while BSH-1 had no effect; BSH, BSH-1, and BSH-2 markedly enhanced the phagocytosis activity and nitric oxide production of the murine macrophage RAW264.7 in a dose-dependent manner. Our results suggest that the water-extractable hemicelluloses from steam-exploded bamboo shavings are naturally acetylated and have immunostimulatory activity.
文摘To fully understand the proliferation of splenocyte in vitro of natto ingredients,two kinds of polysaccharideprotein complexes,named as NPPC-1-b and NPPC-2-a,were extracted and purified from natto by DEAE-52 cellulose ionexchange chromatography and Sephadex G-100 gel filtration chromatography.Their molecular weights were determined by performance gel permeation chromatography to be approximately 26.93 and 357.60 k D for NPPC-1-b and NPPC-2-a,respectively.The two complexes were further characterized by FT-IR,UV-visible spectrophotometry,monosaccharide and amino acid composition analysis.The results showed that NPPC-1-b contained an O-glycopeptide bond,while NPPC-2-a contained an N-glycopeptide bond.NPPC-1-b was mainly composed of mannose(Man),rhamnose(Rha)and arabinose(Ara),with the contents of 67.45%,25.67%and 2.44%,respectively.However,NPPC-2-a was mainly composed of glucose(Glc),mannose(Man),arabinose(Ara),xylose(Xyl)and galactose(Gal),accounting for 36.64%,21.71%,10.35%,9.00%and 5.17%,respectively.Seventeen amino acids were identified in both complexes.NPPC-1-b was mainly composed of glutamic(Glu),proline(Pro),lysine(Lys)and arginine(Arg)with contents of 0.971%,0.791%,0.708%and 0.603%,while NPPC-2-a was mainly composed of Glu,Pro and aspartic(Asp)acid with contents of 0.903%,0.689%and 0.504%.Besides,preliminary in vitro tests showed that NPPC-1-b(100-200μg/m L)and NPPC-2-a(12.5-200μg/m L)exhibited significantly higher immunomodulatory activities against the proliferation of lymphocytes(P 0.05),and the effect of 100μg/m L NPPC-2-a was the best.In respect of cytokines expression,NPPC-1-b and NPPC-2-a significantly enhanced the expression of interleukin-2(IL-2)and interferon-γ(INF-γ),and 50μg/m L NPPC-1-b showed a strong effect on IL-2 secretion,200μg/m L NPPC-2-a exhibited a strong effect on INF-γsecretion.These results suggest that NPPC-1-b and NPPC-2-a can effectively increase immunomodulatory activity.
基金supported by the Research Project of State Key Laboratory of Food Science and Resources,Nanchang University(project no.SKLF-ZZB202314).
文摘Microbial fermentation improves the physicochemical properties,structure,and biological activity of plant polysaccharides,and is an environmentally safer processing method.In this study,Cyclocarya paliurus(C.paliurus)polysaccharide(CP)was obtained through fermentation with Penicillium EF-2.Physicochemical characterisation and macrophage RAW264.7 revealed that fermentation altered the monosaccharide composition and structure of fermented C.paliurus polysaccharide(FCP),enhancing its thermal stability,apparent viscosity,and in vitro immune activity.Metabolomics analysis further indicated that the metabolic pathway of cellulose was activated,facilitating the dissolution of cellulose and hemicellulose in the fermentation broth through the degradation of cellulose in the cell wall of C.paliurus.This process increased polysaccharide production and modified the polysaccharide structure.This study provides a theoretical foundation for the development and utilisation of microbial fermentation-modified polysaccharides and CP.
基金supported by the Youth Fund of the National Natural Science Foundation of China(32302014)Program for National Key R&D Program of China(2022YFF1100202)+2 种基金GanPoJunCai Young Technology Talent Support Program of Jiangxi Province(2025QT01)General Program of Natural Science Foundation of Jiangxi Province(20224BAB205040)Key Laboratory of Bioactive Polysaccharides of Jiangxi Province(20212BCD42016).
文摘In order to better the structure and immunomodulatory activity relationships of Dendrobium officinale polysaccharides,this study partially degraded DOP with a molecular weight of 264 kDa using endo-β-1,4-mannanase.Dendrobium offinale polysaccharides(DOP)and two degraded fractions(DOP-30:51 kDa and DOP-60:28 kDa)were structurally characterized and evaluated for in vitro immunomodulatory activity.Structural analysis indicated that enzymatic hydrolysis of DOP can effectively produce low molecular weight polysaccharides with similar structures but slightly different chemical compositions.The backbone structures of DOPs were all consisted of→4)-β-D-Manp-(1→,→4)-β-D-Glcp-(1→,→4)-2-O-acetyl-β-D-Manp-(1→and→4)-3-O-acetyl-β-D-Manp-(1→.All DOPs enhanced the proliferation and phagocytosis of RAW264.7 macrophages,promoted the secretion of immune effector molecules,and facilitated the polarized of macrophages to the M1 phenotype,as well as the expression of Toll-like receptor 4(TLR4)in vitro.Among them,DOP-60 showed relatively strong immunomodulatory activity.Correlation analysis further indicated that molecular weight(Mw)was most closely correlated with macrophage activation by DOP,suggesting that low molecular weight DOP has a greater potential to activate macrophages.
基金supported by Yunnan fundamental Research Projects(202301as070014)Yunnan Department of science and technology innovation Guidance and technology Enterprise Cultivation Plan(202204BP090031).
文摘Glycoprotein complexes,a kind of structural biomolecules,are characterized by extensive functions,such as immunomodulatory and anti-inflammatory activities.Glycosylation of protein has an important impact on conformational stability and active function of glycoprotein complex.Clarifying the structure of glycoprotein complex is the basis for further exploring its biological activities,and the release of sugar chains is one of the key points in the analysis of glycoprotein structures.Glycoprotein complex can affect the expression of immune-related proteins and factors by activating cell surface receptors,regulating intracellular immune signal transduction,and ultimately play an immunomodulatory role in the body.Meanwhile,the chemical structure and advanced structure of glycoprotein complex can significantly affect the immunomodulatory activity.this review focuses on chemical and advanced structural information of glycoprotein,the regulation mechanism of immunomodulation and the structure-activity relationship,which aims to provide a theoretical basis for the basic research on the immunomodulatory activity of food-derived glycoproteins and the development of related functional products.
基金supported by grants from the Natural Science Foundation of China (81760778)the Fundamental Research Funds for Public-interest Scientific Institution in Xinjiang Uygur Autonomous Region (KYGY2016169)CAMS Innovation Fund for Medical Sciences (2017-I2M-1-012)
文摘Objective:To investigate the immunomodulatory activity of polysaccharides from the roots of Brassica rapa.Methods:The crude polysaccharide from roots of B.rapa(BRP)was extracted and purified to further investigate the active fraction of BRT for inducing macrophage phagocytosis.Results:Effects on RAW264.7 cells demonstrated that BRP behaved better phagocytic capacity and had potent immunomodulatory activity,including increasing production of nitric oxide(NO),tumor necrosis factor a(TNFa)and upregulating mRNA levels of inducible NO synthase(iNOS)and TNFa.Furthermore,modulation of macrophage by BRP was indicated to be mediated via the activation of Akt and nuclear factor-kappa B(NF-κB).Conclusion:The beneficial effects of BRP could be used as an immunotherapeutic adjuvant in treatment of inflammatory diseases.
基金funded by the National Natural Science Foundation of China(32072354)Key R&D Program of Ningxia Hui Autonomous Region(No.2022BBF03016)Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘In order to reveal the intrinsic nature of the reduction or disappearance of biological activity in the processing and preparation of polysaccharides,and realize the effective control of highly active polysaccharides,the correlation between conformation and immunomodulatory activity of lentinan under different subcritical water temperatures was investigated.The results showed that,compared with the lentinan extracted by hot water(HW-L),with the increase of temperature(100–160℃),the molecular weight of lentinans decreased(5.041×10^(5)–1.754×10^(6) g/mol)and the rigidity of the chain weakened.The chains gradually loosened and a rigid-flexible transition occurred.At 160°C,the conformation of lentinan completely changed from triple helix to random coil.In-vitro cell experiments showed that,lentinan at 120℃ could more efficiently promote the proliferation and phagocytosis of RAW264.7 cells,and significantly promote the secretion of NO,TNF-α,IL-6 and IL-1β,exhibiting stronger immunomodulatory activity.But the activity of lentinan decreased sharply at 150–160℃.These results suggest a significant correlation between polysaccharide chain conformation and immunomodulatory activity under different subcritical water temperature conditions.By adjusting the temperature of subcritical water,the chain conformation of polysaccharides can be controlled,resulting in more efficient extraction of highly active polysaccharides.
基金supported by the National Key Research and Development Program of China(The integration and demonstration of key technologies of characteristic cash crops,fruit and vegetable industry in Qinba Mountain area of Shaanxi Province,No.2022YFD1602000)the National Natural Science Foundation of China(No.32272428,31801491)+4 种基金the Scientific Program Funded by Xi’an Science and Technology Bureau(No.22NYYF032)Young Talent Lifting Project Funded by Shaanxi Association for Science and Technology(No.20220216)National Foreign Expert Project Funded by the Ministry of Science and Technology of China(G2022041012L)Xi’an Weiyang District of Technology and Industrial Information Bureau(No.202134)Shaanxi Administration of Traditional Chinese Medicine(SZY-KJCYC-2023-014).
文摘Stipes are the major waste from the processing of Lentinus edodes.To make full use of L.edodes stipes(LES),differ-ent fractions of LES polysaccharides(LESPs)were first obtained by water extraction and gradient ethanol precipitation.Afterwards,the LES residues were treated with an optimal combination of Aspergillus niger and Saccharomyces cerevisiae for the preparation of soluble/insoluble dietary fibers(LESS/LESI)using the response surface methodology and the Box-Behnken design.Subsequently,the in vitro immunomodulatory activity of LESPs and LESS,as well as the adsorption capacities of LESI were evaluated.The results showed that LESPs were neutral polysaccharides,mainly containing glucose.The optimal parameters for modifying the residues of LES were the followings:4%(w/w)A.niger,8%(w/w)S.cerevisiae,31℃,3 d,and a solid-liquid ratio of 1:12.5 in a yield of 14.73%/82.45%of LESS/LESI,respectively.The in vitro immunomodulatory activity assays revealed that LESPs and LESS had potent immunostimulatory activity to increase phagocytosis,acid phosphatase activity and nitric oxide production of RAW264.7 murine cell macrophages.The evaluation of adsorption capacities revealed that LESI owned stronger water holding capacity,oil holding capacity and water swelling capacity.This research could provide an effective way to fully utilize discarded L.edodes stipes with high added-value.
基金financially supported by the Research and Development Fund,Burapha University(Grant no.12/2562&10/2565)the Science Innovation Facility,Faculty of Science,Burapha University(SIF-IN-60300003)+2 种基金the Center of Excellence for Innovation in Chemistry(PERCH-CIC)the Commission on Higher Education,Ministry of Education,Thailandthe Scientific Instruments Center,School of Science,King Mongkut’s Institute of Technology Ladkrabang.
文摘Levan is a fructose homopolymer obtained from both plants and microorganisms.Microbial levan is typically produced in a variety of molecular weights(MW).Previous studies have shown that different MW of levan exhibit different biological activities.Though levan was reported for its immunomodulatory effect by increasing nitric oxide(NO)production in RAW264.7 macrophage cells,whether its MW can affect this activity remains unknown.In this study,the effect of different levan MW from Bacillus subtilis on its immunoregulatory properties was investigated.B.subtilis was cultivated using various cultivation parameters to obtain levan of different MW.Three weight average MW of levan,>8×10^(5) Da(M1),1.5×10^(4) Da(M2)and 3.7×10^(3) Da(M3),were selected to test for their effect on modulating NO levels in RAW264.7 cells.Our results showed that M2 increased NO production in a dose-dependent manner,and more effectively than that of M1 and M3.Consistent with these findings,M2 significantly stimulated inducible nitric oxide synthase(iNOS)and cyclooxygenase-2(COX2)protein expression,while less pronounced effects were observed in the cells treated with M1 and M3.Therefore,our results demonstrate that various MW of levan have varying effects on its immunoregulatory activities in RAW264.7 cells.Furthermore,our findings suggest that the size of levan should be taken into account when employing levan as one of the active ingredients in functional foods and immunomodulatory products.
文摘Background:Lysozyme is a naturally occurring antimicrobial protein with known enzymatic and immunomodulatory properties.In addition to the well-characterized monomeric form,a dimeric form of lysozyme is clinically used as an immunomodulatory drug.However,the biological activity of higher-order oligomers remains poorly understood,particularly in the context of innate immune signaling.Objective:This study aimed to develop a simplified method for lysozyme oligomerization and to characterize the resulting preparations with respect to their antimicrobial and immunomodulatory activity,particularly their ability to activate the nuclear factor kappa B signaling pathway.Methodology:Lysozyme hydrochloride was thermochemically modified using hydrogen peroxide at 90℃for 20 min,followed by catalase neutralization.Size-exclusion high-performance liquid chromatography was used to quantify oligomer content.Enzymatic activity against Gram-positive bacteria was assessed spectrophotometrically,while antibacterial activity against Gram-negative bacteria was evaluated by turbidimetric assay.Immunomodulatory properties were examined using THP1-Blue^(TM)NF-κB reporter cells.Results:The proposed method enabled efficient oligomerization without the need for pH adjustment or multistep procedures.Oligomer content increased proportionally with hydrogen peroxide concentration and was inversely correlated with enzymatic(muramidase)activity.All modified preparations exhibited approximately two-fold increased antibacterial activity against Gram-negative bacteria compared to native lysozyme.Notably,the oligomer-rich preparations induced significantly higher NF-κB activation in THP1-Blue^(TM)cells(up to three-fold compared to native lysozyme),suggesting enhanced immunomodulatory potential.Conclusions:Thermochemically generated lysozyme oligomers retain and even improve biological activity despite reduced enzymatic capacity.Their ability to activate innate immune signaling highlights their potential as dual-action bioactive agents with antimicrobial and immunostimulatory properties.
基金supported by the Natural Science Foundation of Tianjin(No.24JCYBJC00440).
文摘Chroogomphis rutilus is a kind of delicious edible fungus rich in bioactive components such as polysaccharides,and has high nutritional values.However,the researches on the structure-activity relationship of polysaccharide components are still ambiguous.In this study,the C.rutilus water-extracted polysaccharide(CRWP)and alkali-extracted polysaccharide(CRAP)were obtained using deionized water and weak alkali solutions,respectively,and purified by dialysis,and the gut microbiota mediated immune regulatory activities were further studied.Structural analysis results showed that both CRWP and CRAP exhibited typical polysaccharide characteristics,showing the main chains ofβ-(1→6)-Manp andβ-(1→6)-Glcp linkedβ-(1→6)-Manp,respectively,with the molecular weights of 1.91×10^(7) Da and 2.19×10^(7) Da.In cyclophosphamide induced immune-injured mice,CRWP and CRAP effectively regulated the Lactobacillaceae/Lactobacillus mediated plant hormone signal trans-duction pathway and Akkermansiacae/Akkermansia mediated lysine degradation pathway,respectively.Besides,CRWP exhibited superior immunomodulatory effects on the proportions of CD19+B cells and CD3+T cells in peripheral blood compared with CRAP.These findings provide experimental data and theoretical basis for the development and application of C.rutilus polysaccharides in functional food fields.
基金supported by a grant from the 2023 Jiangsu Province Industry-University-Research Cooperation Project(BY20230427)the Yancheng Science and Technology Planning Project(YCBK202250)the Yancheng Institute of Technology School-level Talent Project(xjr2021025).
文摘This study investigates the efficacy of polysaccharides derived from Osmunda japonica Thunb in the context of immunoinflammation and elucidates its underlying mechanisms.The findings demonstrate that Osmunda japonica Thunb polysaccharides(OP)significantly enhances microcirculation in vivo,facilitates immune regu-lation,and markedly promotes cell proliferation.Notably,the high-dose OP group exhibited a 45.18%inhibition rate on ear edema in mice,with a maximum vasodilatory effect of 16.72%.Additionally,after 24 h of OP stimulation of macrophages,the most pronounced promotion of activity was observed at 151.36%when the OP concentration reached 100μg/mL.OP also stimulates the secretion of nitric oxide(NO)and pro-inflammatory cytokines,including interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-α),prostaglandin E2(PGE2),and interleukin-1β(IL-1β),indicating its potent biological activity.Furthermore,OP promotes macrophage activation and NO release by activating the mitogen-activated protein kinase(MAPK)and nuclear factor-kappa B(NF-κB)signaling pathways,with particular emphasis on the NF-κB pathway,as well as c-Jun N-terminal kinase(JNK)and p38 MAPK within the MAPK pathway.These findings not only elucidate the mechanisms by which OP functions in the realm of immune inflammation but also provide a scientific foundation for the development of immune-regulating food products,thereby contributing to enhanced human health.
基金financially supported by the National Natural Science Foundation of China(32172211)the Program for Science&Technology Innovation Talents in Universities of Henan Province(22HASTIT037).
文摘Mustard seeds is a traditional Chinese natural product of pharmaceutical and dietary origin,rich in polyphenols,flavonoids,and other active ingredients,exhibiting multiple bioactivities.In order to improve the yield,polyphenols from brown and white mustard seeds were extracted under better circumstances using Response Surface Methodology(RSM).Subsequently,components were assessed using LC-MS/MS.A total of 8 phenolic compounds and 3 flavonoid compounds were identified in brown mustard seeds extracts(BMSE),and 14 phenolic compounds and 4 flavonoid compounds were identified in white mustard seeds extracts(WMSE).Meanwhile,the biological activities of BMSE and WMSE were compared via in vitro free radical scavenging,hepatocyte oxidative injury protection,and macrophage immunoregulation models.The results showed that both BMSE and WMSE exhibited antioxidant activity and oxidative damage protection activity on HL-7702 cells,and BMSE was more effective.The viability of HL-7702 cells induced oxidative damage by hydrogen peroxide treated with BMSE and WMSE was increased by 36.7%and 32.8%,respectively.WMSE exhibited better in vitro immunomodulatory activities than BMSE,including proliferation promoting,phagocytosis,and NO release abilities on RAW264.7 cells.This study can contribute to the application of mustard seeds polyphenols in the field of functional foods,as well as provide a direction for the high-value utilization of mustard seeds.
基金support by the Establishment of Sino-Austria“Belt and Road”Joint Laboratory on Traditional Chinese Medicine for Severe Infectious Diseases and Joint Research,China(Grant No.:2020YFE0205100)the National Key Research and Development Program of China(Grant Nos.:2020YFA0908000,2022YFC2303600)+9 种基金the Distinguished Expert Project of Sichuan Province Tianfu Scholar(Grant No.:CW202002)the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine,China(Grant No.:ZYYCXTD-C-202002)the National Natural Science Foundation of China(Grant Nos.:82141001,82274182,82074098,82173914)the China Academy of Chinese Medical Sciences(CACMS)Innovation Fund,China(Grant Nos.:CI2021A05101,CI2021A05104)the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences(Grant No.:CI2021B014)the Science and Technology Foundation of Shenzhen,China(Grant No.:JCYJ20210324115800001)the Science and Technology Foundation of Shenzhen,China(Shenzhen Clinical Medical Research Center for Geriatric Diseases),the National Key R&D Program of China Key Projects for International Cooperation on Science,Technology and Innovation(Grant No.:2020YFE0205100)the Fundamental Research Funds for the Central Public Welfare Research Institutes,China(Grant Nos.:ZZ14-YQ-050,ZZ14-YQ-051,ZZ14-YQ-052,ZZ14-FL-002,ZZ14-ND-010,ZZ15-ND-10),Shenzhen Governmental Sustainable Development Fund,China(Grant No.:KCXFZ20201221173612034)Shenzhen key Laboratory of Kidney Diseases,China(Grant No.:ZDSYS201504301616234)Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties,China(Grant No.:SZGSP001).
文摘Sepsis is characterized by a severe and life-threatening host immune response to polymicrobial infection accompanied by organ dysfunction.Studies on the therapeutic effect and mechanism of immunomodulatory drugs on the sepsis-induced hyperinflammatory or immunosuppression states of various immune cells remain limited.This study aimed to investigate the protective effects and underlying mechanism of artesunate(ART)on the splenic microenvironment of cecal ligation and puncture-induced sepsis model mice using single-cell RNA sequencing(scRNA-seq)and experimental validations.The scRNA-seq analysis revealed that ART inhibited the activation of pro-inflammatory macrophages recruited during sepsis.ART could restore neutrophils’chemotaxis and immune function in the septic spleen.It inhibited the activation of T regulatory cells but promoted the cytotoxic function of natural killer cells during sepsis.ART also promoted the differentiation and activity of splenic B cells in mice with sepsis.These results indicated that ART could alleviate the inflammatory and/or immunosuppressive states of various immune cells involved in sepsis to balance the immune homeostasis within the host.Overall,this study provided a comprehensive investigation of the regulatory effect of ART on the splenic microenvironment in sepsis,thus contributing to the application of ART as adjunctive therapy for the clinical treatment of sepsis.
基金funded by Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma of Thammasat UniversityThammasat University Research fund under the TU Research Scholar(Contract No.03/2561)。
文摘Objective:To evaluate the cytotoxic,apoptotic,mutagenic and immunomodulatory activities of Kaempferia galanga Linn.(KG)extract and ethyl-p-methoxycinnamate(EPMC)in vitro.Methods:The present study investigated the cytotoxic[using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphe nyl-2-H-tetrazolium bromide test],apoptotic(using a mitochondrial membrane potential assay),mutagenic(using a micronucleus test)and immunomodulatory(using flow cytometry)activities of the ethanolic extract of KG and its bioactive component,EPMC,against two cholangiocarcinoma(CCA)cell lines,CL-6 and HuCCT1,and one normal human cell line,OUMS-36 T-1 F.Results:Both KG extract and EPMC exhibited moderate cytotoxic activity against both CCA cells.The cytotoxic activity was supported by their concentration-dependent induction of apoptosis.CL-6 was most sensitive(3–4 fold)and selective to 5-fluorouracil(5-FU),compared with KG extract and EPMC[median half inhibiting concentration(IC50)and selectivity index(SI)were 23.01 lg/mL and 17.32;78.41 lg/mL and 4.44;100.76 lg/mL and 2.20,respectively for 5-FU vs.KG extract vs.EPMC].HuCCT1 was relatively more sensitive and selective to 5-FU and EPMC than KG extract[median IC50 and SI were 66.03 lg/mL and6.04;60.90 lg/mL and 3.65;156.60 lg/mL and 2.23,respectively for 5-FU vs.EPMC vs.KG extract].EPMC produced relatively potent cytotoxic activity against polymorphonuclear cells(IC50=92.20 lg/mL).KG extract and EPMC exhibited concentration-dependent mutagenic activity,as well as inhibition of tumor necrosis factor-a and interleukin-6.Conclusion:Considering cytotoxic,apoptotic,immunomodulatory and mutagenic activities,further development of KG as a drug candidate is likely to focus on the oral pharmaceutical formulation of a standardized KG extract rather than isolated compounds.
基金supported by the Fujian Provincial Natural Science Foundation of China[2023J05288,2023]the Xiamen Medical and Health Guidance Project,China[3502Z20224ZD1297,2022]+3 种基金the Research Program of the Department of Education from Fujian Province[No.JAT241169,2024]the Engineering Research Center of Natural Cosmeceuticals College of Fujian Province Fund(Xiamen Medical College)(No.XMMC-OP2024010)the Joint Funds for the innovation of science and Technology,Fujian Province[2024Y9708]the Xiamen Medical College Undergraduate Innovation and Entrepreneurship Training Program[X202312631068,2024].
文摘Moderate steaming(4 h)enhances immunomodulatory activities of Polygonatum cyrtonema polysaccharides(PCPs);however,the bioactive fractions and their underlying mechanisms remain unclear.Herein,fractionation of steamed rhizomes(PCP-4h)yielded five active fractions:two neutral polysaccharides(D1 and D2)and three acidic polysaccharides(D3-D5).Each fraction has a distinct molecular weight and monosaccharide composition.Acidic polysaccharides demonstrated superior immunomodulatory activities over neutral polysaccharides.RNA-seq revealed 3639,3668,and 3663 differentially expressed genes(DEGs)induced by D3-D5 that were enriched in TLR4-mediated MAPK(p-p38,p-ERK1/2 and p-JNK)and NF-κB(p-IκBαand p-p65)pathways.D3 exerted the strongest pathway effect,correlating with its superior bioactivity.Acidic polysaccharide fractions were identified as key bioactive drivers of PCP-4h immunomodulation via the TLR4-MAPK/NF-κB signaling pathway,facilitating the enhancement of bioactivity through optimized processing methods.
基金supported by the National Key Research and Development Program of China(No.2022YFD2200804).
文摘Russula vinosa Lindblad(R.vinosa Lindblad)is a nutrient-rich wild edible fungus,abundant in car-bohydrates.In this study,two polysaccharides(Russula polysaccharides extracted from 1%KOH(RP-1)and Russula polysaccharides extracted from 5%KOH(RP-5))were extracted from Russula fruit bodies using KOH-graded extraction technology.The molecular weights of RP-1 and RP-5 were 187000 and 97300 u,respectively.Their glycosyl compositions(galactose꞉glucose꞉xylose꞉mannose,i.e.,Gal꞉Glu꞉Xyl꞉Man)were 0.27:1.00:0.01:0.16 for RP-1 and 0.12:1.00:0.03:0.19 for RP-5.Nuclear magnetic resonance(NMR)analysis revealed that the main structural component of RP-1 was→3,6)-β-d-Glu p-(1→,with a→6)-β-d-Glu p-(1→residue linked at sites 1 and 6,and a→3)-β-d-Glu p-(1→residue linked at sites 3.The RP-5 shared this structure with an additional→4)-β-d-Man p-(1→residue attached to the→3)-β-d-Glu p-(1→.Phagocytosis assay demonstrated that RP-5,with a lower molecular weight,lower galactose content,and higher xylose and man-nose content,enhanced RAW 264.7 cell phagocytic activity by 121.04%,outperforming RP-1,which showed a 42.15%increase at the same concentration of 600𝜇g/mL.Furthermore,both RP-1 and RP-5 reduced the release of inflammatory factors and induced the nuclear translocation of the nuclear transcription factor-𝜅B(NF-𝜅B)pathway in RAW 264.7 cells.This study provided insights into the structural characteristics and immunomodulatory properties of Russula polysac-charides,offering potential for further applications in bioactive compound development.
基金supported financially by the Hong Kong Polytechnic University.
文摘Polysaccharides from Lentinula edodes mushrooms(LePS)are well-known for their immunomodulatory activities,which may have a functional connection with probiotic fermentation in the gut microbiota.This study was to evaluate the bifidogenic properties and impact of Bifidobacterial fermentation on the LePS molecules and immunoactivities.Two LePS fractions,LePS-40(3.97×10^(7) Da)and LePS-80(1.43×10^(5) Da)with differences in molecular weight(MW)and chemical composition were isolated from the mushroom hot-water extract and fermented with a Bifidobacterium breve strain.The higher-MW fraction LePS-40 was more significantly consumed and utilized by the bacteria for growth and acetic acid production during the fermentation,due probably to its higher total carbohydrate content and glucose-abundant composition.The Bifidobacterial fermentation caused a notable MW reduction of both LePS fractions and,more interestingly,also led to a higher immunostimulatory activity in RAW 264.7 macrophage cells.Further assessment of the separated fractions by ultrafiltration of the fermentation liquid(digesta)suggested that the immunoactivity was mainly attributed to the partially degraded LePS instead of the small-molecule metabolite products derived from the Bifidobacterial fermentation.In summary,monosaccharide composition was a more significant determinant than MW on the bifidogenic properties of LePS and the immunomodulatory activities after fermentation.
基金The National Key Research and Development Project(2021YFD2100702)The Liaoning Provincial Department of Education Funding for Basic Scientific Research Project in University,China(LJKZZ20220062).
文摘In this study,casein hydrolysate was prepared by a two-step enzymatic method,and it was demonstrated that casein hydrolysate has good immunomodulatory activity in vitro and in vivo by cell and animal experiments.The casein hydrolysate prepared by two-step enzymatic method was characterized by high hydrolysis,of which 62.70%had molecular weight less than 1000 Da.Interestingly,the casein hydrolysate prepared by two-step enzymatic hydrolysis could activate macrophages and promote the phagocytosis of RAW 264.7 cells and the production of inflammatory factors.Additionally,the two-step enzymatic preparation of casein hydrolysate restored T-lymphocyte proliferation and natural killer cell activity and promoted the production of immunoglobulins and serum cytokines(IL-6,IL-1βand TNF-α)in immunocompromised treated mice.This study provides new ideas for developing novel functional foods or nutraceuticals.
