Exosomes(Exos)are extracellular vesicles secreted by cells and serve as crucial mediators of intercellular communication.They play a pivotal role in the pathogenesis and progression of various diseases and offer promi...Exosomes(Exos)are extracellular vesicles secreted by cells and serve as crucial mediators of intercellular communication.They play a pivotal role in the pathogenesis and progression of various diseases and offer promising avenues for therapeutic interventions.Exos derived from mesenchymal stem cells(MSCs)have significant immunomodulatory properties.They effectively regulate immune responses by modulating both innate and adaptive immunity.These Exos can inhibit excessive inflammatory responses and promote tissue repair.Moreover,they participate in antigen presentation,which is essential for activating immune responses.The cargo of these Exos,including ligands,proteins,and microRNAs,can suppress T cell activity or enhance the population of immunosuppressive cells to dampen the immune response.By inhibiting lymphocyte proliferation,acting on macrophages,and increasing the population of regulatory T cells,these Exos contribute to maintaining immune and metabolic homeostasis.Furthermore,they can activate immune-related signaling pathways or serve as vehicles to deliver microRNAs and other bioactive substances to target tumor cells,which holds potential for immunotherapy applications.Given the immense therapeutic potential of MSC-derived Exos,this review comprehensively explores their mechanisms of immune regulation and therapeutic applications in areas such as infection control,tumor suppression,and autoimmune disease management.This article aims to provide valuable insights into the mechanisms behind the actions of MSC-derived Exos,offering theoretical references for their future clinical utilization as cell-free drug preparations.展开更多
The surface macromolecules of probiotic bacteria play crucial roles in modulating immune responses in the host.Exopolysaccharide(EPS)from lactic acid bacteria(LAB)have been widely reported to exhibit immunomodulatory ...The surface macromolecules of probiotic bacteria play crucial roles in modulating immune responses in the host.Exopolysaccharide(EPS)from lactic acid bacteria(LAB)have been widely reported to exhibit immunomodulatory activity.In this study,the EPS biosynthesis gene cluster of Lacticaseibacillus paracasei S-NB was analyzed and a deletion mutant S-NBΔ7576(two genes S-NB_2175/wze and S-NB_2176/wzd were responsible for the chain length determination and export of EPS)was successfully constructed,resulting a 40.02%decrease in the production of EPS.The deletion of wze and wzd had little effect on the monosaccharide composition and major groups of the two EPS fractions(BEPS1 and BEPS2).Both BEPS1 and BEPS2 could inhibit the transcriptional level of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),inducible nitric oxide synthase(i NOS)and cyclooxygenase-2(COX-2)mRNA in RAW 264.7 cells induced by lipopolysaccharide(LPS),and enhance host immune tolerance via suppressing NF-κB and MAPK signaling.Notably,the S-NBΔ7576 mutant supplied with the BEPS1/BEPS2 exhibited more significant inhibition of cytokines production and the phosphorylation of p65 and c-Jun N-terminal kinase(JNK)in LPS-stimulated cells compared with the S-NBΔ7576 mutant alone.Our study provided the immunomodulatory effect of BEPS1 and BEPS2 from L.paracasei S-NB,in which the wze and wzd genes associated with EPS biosynthesis may play an important role.展开更多
The biological activity of plant polysaccharides can be enhanced by sulfated modification.In this study,the immunomodulatory effect of sulfated Cyclocarya paliurus polysaccharides(SCP3)on macrophages RAW264.7 and its ...The biological activity of plant polysaccharides can be enhanced by sulfated modification.In this study,the immunomodulatory effect of sulfated Cyclocarya paliurus polysaccharides(SCP3)on macrophages RAW264.7 and its potential molecular mechanism were investigated.Results showed that SCP3 at 25-100μg/m L increased viability and improved phagocytosis of RAW264.7 cells.Meanwhile,SCP3 could activate mitogen-activated protein kinase(MAPK)and nuclear factor kappa B(NF-κB)signaling pathways,which increased the phosphorylation of Erk1/2,JNK,p38 and NF-κB p65,promoting secretion of cytokines tumor necrosis factorα(TNF-α),interleukin 6(IL-6)and nitric oxide(NO)as well as the production of reactive oxygen species(ROS).In addition,Toll-like receptor 4(TLR4)receptor inhibitors were able to block the production of NO and TNF-αby SCP3-stimulated macrophages.Based on Western blot analysis and validation using specific inhibitors against MAPK and NF-κB signaling pathways,the results demonstrated that SCP3 induced macrophages activation and enhanced TNF-αand NO production via TLR4-mediated MAPK and NF-κB pathways.In summary,SCP3 has significant immunomodulatory potential.The underlying molecular mechanism was that SCP3 activates macrophages via TLR4 receptors to promote ROS production,which in turn activates the downstream MAPK/NF-κB signaling pathway and then increases the secretion levels of cytokines and NO.展开更多
Diarrhea is a common enteric disease in piglets that leads to high mortality and economic losses in swine production worldwide.Antibiotics are commonly used to prevent or treat diarrhea in piglets.However,irrational a...Diarrhea is a common enteric disease in piglets that leads to high mortality and economic losses in swine production worldwide.Antibiotics are commonly used to prevent or treat diarrhea in piglets.However,irrational antibiotic use contributes to the development of resistance in bacteria and antibiotic residues in animal products,threatening public health,while causing gut microbiota dysbiosis and antibiotic-resistant bacterial infection in piglets.Therefore,the quest for alternative products(such as probiotics,prebiotics,organic acids,enzymes;essential oils,medium-chain fatty acids,zinc,and plant extracts)has recently been clearly emphasized through the increase in regulations regarding antibiotic use in livestock production.These antibiotic alternatives could lower the risk of antibiotic-resistant bacteria and meet consumer demand for antibiotic-free food.Several antibiotic alternatives have been proposed,including immunomodulatory probiotics,as candidates to reduce the need for antimicrobial therapy.Many studies have revealed that probiotics can avert and cure bacterial diarrhea by regulating the gut function and immune system of piglets.In this review,we focus on the major pathogenic bacteria causing piglet diarrhear the research sta of using probiotics to prevent and treat diarrhea,their possible mechanisms,and the safety issues related to the use of probiotics.Supplementation with probiotics is a possible alternative to antibiotics for the prevention or treatment of bacterial diarrhea in piglets.Furthermore,probiotics exe rt beneficial effects on feed efficiency and growth performance of piglets.Therefore,appropriate selection and strategies for the use of probiotics may have a positive effect on growth performance and also reduce diarrhea in piglets.This review provides useful information on probiotics for researchers,pig nutritionists,and the additive industry to support their use against bacterial,diarrhea in piglets.展开更多
The polysaccharides from edible fungus showed many kinds of biological activities,including anti-tumor,immunomodulatory,anti-inflammatory,anti-diabetes,improving functional constipation activities.In particular,the im...The polysaccharides from edible fungus showed many kinds of biological activities,including anti-tumor,immunomodulatory,anti-inflammatory,anti-diabetes,improving functional constipation activities.In particular,the immunomodulatory effects have been paid more and more attention by scholars,but there was no systematic introduction of their immunomodulatory mechanism.So,this review introduced the immunomodulatory effects and mechanism of edible fungus polysaccharides in recent years,and then the relationships between structure and immunomodulatory effect were also discussed.展开更多
The present study was designed to evaluate the immune-modulating effects of the polysaccharide from Grifola frondosa(GFP) by using mouse peritoneal macrophage and cytoxan(CTX) induced immunosuppression models. Our res...The present study was designed to evaluate the immune-modulating effects of the polysaccharide from Grifola frondosa(GFP) by using mouse peritoneal macrophage and cytoxan(CTX) induced immunosuppression models. Our results from the phagocytotic and mononuclear phagocytic system function assays showed that GFP-A(one component from GFP) stimulated the phagocytosis of the phagocytes. The splenocyte proliferation assay showed that GFP-A acted the effect combing Con A or LPS in splenocyte proliferation. The results showed that GFP-A increased indices of thymus and spleen, the levels of LDH and ACP in the spleen, the m RNA levels of IL-1β, IL-2, IL-6 and IFN-γ in splenocyte. And GFP-A also significantly increased the expression of CD4^+ and CD8^+ splenic T lymphocytes, which were suppressed by the CTX in peripheral blood. In conclusion, our results indicate that the GFP-A is involved in immunomodulatory effects leading to its modulatory effects on immunosuppression.展开更多
It is currently difficult for conventional treatments of acute pancreatitis (AP), which primarily consist of anti-inflammatory therapies, to prevent the progression of AP or to improve its outcome. This may be because...It is currently difficult for conventional treatments of acute pancreatitis (AP), which primarily consist of anti-inflammatory therapies, to prevent the progression of AP or to improve its outcome. This may be because the occurrence and progression of AP, which involves various inflammatory cells and cytokines, includes a series of complex immune events. Considering the complex immune system alterations during the course of AP, it is necessary to monitor the indicators related to immune cells and inflammatory mediators and to develop more individualized interventions for AP patients using immunomodulatory therapy. This review discusses the recent advances in immunomodulatory therapies. It has been suggested that overactive inflammatory responses should be inhibited and excessive immunosuppression should be avoided in the early stages of AP. The optimal duration of anti-inflammatory therapy may be shorter than previously expected (< 24 h), and appropriate immunostimulatory therapies should be administered during the period from the 3rd d to the 14th d in the course of AP. A combination therapy of anti-inflammatory and immune-stimulating drugs would hopefully constitute an alternative to anti-inflammatory drug monotherapy. Additionally, the detection of the genotypes of critical inflammatory mediators may be useful for screening populations of AP patients at high risk of severe infections to enable the administration of early interventions to improve their prognosis. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.展开更多
The most common age-related neurodegenerative disease is Alzheimer's disease(AD) characterized by aggregated amyloid-β(Aβ) peptides in extracellular plaques and aggregated hyperphosphorylated tau protein in intr...The most common age-related neurodegenerative disease is Alzheimer's disease(AD) characterized by aggregated amyloid-β(Aβ) peptides in extracellular plaques and aggregated hyperphosphorylated tau protein in intraneuronal neurofibrillary tangles,together with loss of cholinergic neurons,synaptic alterations,and chronic inflammation within the brain.These lead to progressive impairment of cognitive function.There is evidence of innate immune activation in AD with microgliosis.Classically-activated microglia(M1 state) secrete inflammatory and neurotoxic mediators,and peripheral immune cells are recruited to inflammation sites in the brain.The few drugs approved by the US FDA for the treatment of AD improve symptoms but do not change the course of disease progression and may cause some undesirable effects.Translation of active and passive immunotherapy targeting Aβ in AD animal model trials had limited success in clinical trials.Treatment with immunomodulatory/anti-inflammatory agents early in the disease process,while not preventive,is able to inhibit the inflammatory consequences of both Aβ and tau aggregation.The studies described in this review have identified several agents with immunomodulatory properties that alleviated AD pathology and cognitive impairment in animal models of AD.The majority of the animal studies reviewed had used transgenic models of early-onset AD.More effort needs to be given to creat models of late-onset AD.The effects of a combinational therapy involving two or more of the tested pharmaceutical agents,or one of these agents given in conjunction with one of the cell-based therapies,in an aged animal model of AD would warrant investigation.展开更多
Parkinson’s disease（PD） is an age-related neurodegenerative disease for which the characteristic motor symptoms emerge after an extensive loss of dopamine containing neurons.The cell bodies of these neurons are pre...Parkinson’s disease（PD） is an age-related neurodegenerative disease for which the characteristic motor symptoms emerge after an extensive loss of dopamine containing neurons.The cell bodies of these neurons are present in the substantia nigra,with the nerve terminals being in the striatum.Both innate and adaptive immune responses may contribute to dopaminergic neurodegeneration and disease progression is potentially linked to these.Studies in the last twenty years have indicated an important role for neuroinflammation in PD through degeneration of the nigrostriatal dopaminergic pathway.Characteristic of neuroinflammation is the activation of brain glial cells,principally microglia and astrocytes that release various soluble factors.Many of these factors are proinflammatory and neurotoxic and harmful to nigral dopaminergic neurons.Recent studies have identified several different agents with immunomodulatory properties that protected dopaminergic neurons from degeneration and death in animal models of PD.All of the agents were effective in reducing the motor deficit and alleviating dopaminergic neurotoxicity and,when measured,preventing the decrease of dopamine upon being administered therapeutically after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,6-hydroxydopamine,rotenone-lesioning or delivery of adeno-associated virus-α-synuclein to the ventral midbrain of animals.Some of these agents were shown to exert an anti-inflammatory action,decrease oxidative stress,and reduce lipid peroxidation products.Activation of microglia and astrocytes was also decreased,as well as infiltration of T cells into the substantia nigra.Pretreatment with fingolimod,tanshinoine I,dimethyl fumarate,thalidomide,or cocaine-and amphetamine-regulated transcript peptide as a preventive strategy ameliorated motor deficits and nigral dopaminergic neurotoxicity in brain-lesioned animals.Immunomodulatory agents could be used to treat patients with early clinical signs of the disease or potentially even prior to disease onset in those identified as having pre-disposing risk,including genetic factors.展开更多
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
Objective:To explore the immunomodulatory properties of 80% ethanol extract and butanol fraction of Gentiana olivieri(G. olivieri) Griseb on Balb/C mice.Methods:The study was performed with basic models of immunomodul...Objective:To explore the immunomodulatory properties of 80% ethanol extract and butanol fraction of Gentiana olivieri(G. olivieri) Griseb on Balb/C mice.Methods:The study was performed with basic models of immunomodulation such as the humoral antibody response(hemoglutination antibody titres), cell mediated immune response(delayed type hypersensitivity and in vivocarbon clearance or phagocytosis). Ethanol(80%) extract of flowering aerial parts of G.olivieriand its butanol fraction were administered p.o.(orally) to the mice. Levamisole, 2.5 mg/kg was used as standard drug.Results:There was a potentiation of immune response to sheep red blood cells by cellular and humoral mediated mechanisms comparable to levamisole(2.5 mg/kg) by both 80% ethanol extract and the butanol fraction at doses of 50-200 mg/kg in male Balb/C mice. Both significantly(P<0.01) potentiated the humoral immune response in cyclophosphamide(250 mg/kg)immunosupressed mice at 100 and 200 mg/kg of each extract and fraction as compared to control.The potentiation of delayed type hypersensitivity response was statistically significant(P<0.01) at200 mg/kg of ethanol extract and 100, 200 mg/kg of butanol fraction as compared to control. The phagocytosis was significant at 200 mg/kg with butanol fraction ofG. olivieri.Conclusions:The results reveal the immunostimulant effects of plantG. olivieriin mice by acting through cellular and humoral immunity in experimental models of immunity in mice. Butanol fraction is the most effective at a dose level of 200 mg/kg.展开更多
Seaweed Complex Preparation （SCP） is a clinical traditional Chinese medicine preparation which is composed of seven traditional Chinese herbs, and it has been used for treatment of lung cancer, liver cancer and dige...Seaweed Complex Preparation （SCP） is a clinical traditional Chinese medicine preparation which is composed of seven traditional Chinese herbs, and it has been used for treatment of lung cancer, liver cancer and digestive cancer. However, little infor- mation is available about the pharmacodynamic basis. The antitumor, immunomodulatory and free radical scavenging effects of SCP were evaluated in this study. Transplanted tumor in vivo method was used to determine the antitumor effect. The effects on spleno- cyte proliferation and phagocytosis of macrophages in tumor-bearing mice were measured by the MTT method and the phagocytizing cock red blood cell （CRBC） method respectively. The scavenging activities of SCP on DPPH and hydroxyl radicals in vitro were investigated. It was found that the medium-dose and high-dose of SCP could significantly inhibit the growth of transplanted hepatic tumor of murine hepatocarcinoma cell line H22, and promote proliferation of splenocytes and phagocytosis of macrophages. SCP possessed noticeable scavenging activities on DPPH and hydroxyl radicals. The antiturnor effects of SCP might be achieved by im- proving immune system and scavenging free radicals, which is in accordance with the viewpoint of traditional Chinese medicine in promoting the body resistance and eliminating pathogenic factors for cancer treatment.展开更多
Objective:In our continued efforts to isolate the active immunomodulatory and antiviral constituents of Loranthus micranthus Linn parasitic on Kola acuminata,we set out to fractionate the crude aqueous methanol extrac...Objective:In our continued efforts to isolate the active immunomodulatory and antiviral constituents of Loranthus micranthus Linn parasitic on Kola acuminata,we set out to fractionate the crude aqueous methanol extract of the plant.The establishment of the most potent fraction(s) as well as the isolation of the pure active secondary metabolite responsible for the immune stimulatory and antiviral activities in Eastern Nigeria mistletoe has become very needful.This will enable us prove our assumption that this particular specie is different from the European version,Viscum album.Methods:Five solvents of varying polarity namely n-hexane,chloroform, ethylacetate,acetone and methanol were successively employed in the complete fractionation of the crude aqueous -methanol extract of Eastern Nigerian mistletoe,Loranthus micranthus Linn.,harvested from Kola acuminata in that order.The fractions were dried in-vacuo using a rotary evaporator maintained at a temperature of(40±5)℃.The different fractions were screened for immunomodulatory activity using a universal model:the cellular - mediated delayed type hypersensivity test in experimental mice.This was performed by administering two different dose levels:250 mg/kg and 500 mg/kg of each fraction against standard positive and negative control. Results:Results of the study established dose-dependent immunostimulatory(upregulatory) effects of the five fractions of the extract as the model used in the study with different percentage stimulations compared to controls.At the dose levels of 500 mg/kg and 250 mg/kg body weight,the percentage stimulation observed were as following:chloroform fraction 311.11%and 122.22%,ethyl acetate fraction 193.38%and 95. 56%,n-hexane 155.56%and 3.50%,acetone fraction 95.56%and 51.11%and methanol fraction 68. 89%and 24.44%respectively.Levamisole,a known potent immunostimulant,afforded a stimulation of 68. 89%at a dose of 2.5 mg/kg.Conclusion:The study showed that the order of immunomodulatory potency is chloroform fraction > ethylacetate fraction > hexane fraction > acetone fraction > methanol fraction.Bioassayguided fractionation and purification of the active extracts led to the isolation of pure compounds phytochemically characterized as sterols and flavonoids.This work indicates that the main constituents of our local mistletoe responsible for immunostimulation are the flavonoids,terpenoids and or steroids.Glycosides,carbohydrates, tannins and alkaoids appear to augment the measured activities.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
AIM:To investigate the efficacy of Viusid,a nutritional supplement,as an antioxidant and an immunomodulator in patients with chronic hepatitis C.METHODS:Sixty patients with chronic hepatitis C who were non-responders ...AIM:To investigate the efficacy of Viusid,a nutritional supplement,as an antioxidant and an immunomodulator in patients with chronic hepatitis C.METHODS:Sixty patients with chronic hepatitis C who were non-responders to standard antiviral treatment were randomly assigned to receive Viusid(3 sachets daily,n=30) or placebo(n=30) for 24 wk.The primary outcome was the change in serum malondialdehyde and 4-hydroxyalkenals(lipid peroxidation products).Secondary outcomes were changes in serum tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ) and interleukin-10(IL-10).RESULTS:Statistically significant reductions in serum 4-hydroxyalkenals and malondialdehyde levels were observed in both groups in comparison with pretreatment values,but the patients who received Viusid showed a more marked reduction as compared with the control group(P=0.001).TNF-α levels significantly increased from 6.9 to 16.2 pg/mL(P< 0.01) in the patients who received placebo in comparison with almost unchanged levels,from 6.6 to 7.1 pg/mL(P=0.26),in the patients treated with Viusid(P=0.001).In addition,IL-10 levels were markedly increased in the patients treated with Viusid(from 2.6 to 8.3 pg/mL,P=0.04) in contrast to the patients assigned to placebo(from 2.8 to 4.1 pg/mL,P=0.09)(P=0.01).Likewise,the administration of Viusid markedly increased mean IFN-γ levels from 1.92 to 2.89 pg/mL(P< 0.001) in comparison with a reduction in mean levels from 1.80 to 1.68 pg/mL(P=0.70) in the placebo group(P< 0.0001).Viusid administration was well tolerated.CONCLUSION:Our results indicate that treatment with Viusid leads to a notable improvement of oxidative stress and immunological parameters in patients with chronic hepatitis C.展开更多
Crassostrea sikamea(C.sikamea)is an important edible and medicinal seafood in China.In the present study,a compound named flazin was separated and identified from the ethyl acetate extract of C.sikamea(EAECs)for the f...Crassostrea sikamea(C.sikamea)is an important edible and medicinal seafood in China.In the present study,a compound named flazin was separated and identified from the ethyl acetate extract of C.sikamea(EAECs)for the first time.In addition,the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetra zolium(MTS)assay revealed that EAECs and flazin inhibited the transformation of splenic lymphocytes in vitro.Moreover,flazin(20μg·mL^(−1))altered the populations of splenic lymphocyte subtypes.Real-time quantitative PCR(RT-qPCR)analysis and enzyme-linked immunosorbent assay(ELISA)showed that flazin suppressed the mRNA expression and secretion of TNF-αand IL-2,and reversed Concanavalin A(ConA)-induced mRNA up-regulation and protein secretion of TNF-αand IL-2.Western blot results showed that flazin reversed ConA-induced increases in p-ERK1/2 and p-p38 in splenocytes.In conclusion,flazin exhibits effective immunomodulatory function and may be useful for treating immune-related disorders,which indicates the application potential of C.sikamea as a functional food or immunomodulator.展开更多
Huang Qi(黄芪Astragalus membranaceus)is a well-known and widely used herb in traditional Chinese medicine(TCM)tonic preparations.It has been used for many ailments over the last 2000 years.Flavonoids,saponins,and poly...Huang Qi(黄芪Astragalus membranaceus)is a well-known and widely used herb in traditional Chinese medicine(TCM)tonic preparations.It has been used for many ailments over the last 2000 years.Flavonoids,saponins,and polysaccharides have been shown to be the main compounds responsible for the biological and pharmacological activities,especially the immunomodulatory properties,of such tonic preparations.This review summarizes the published data on Astragalus extracts and fractions and the natural compounds responsible for the immunomodulatory activity with special reference to the modulation of nuclear factor-kappa B and related pathways(e.g.,Nrf2).In addition,this review highlights the importance of Astragalus membranaceus in TCM for treating patients with diseases related to immunocompromised conditions,such as cancer and diabetes.展开更多
Objective: To evaluate the in vitro and in vivo effect of the Algerian propolis ethanolic extract(EEP) against Echinococcus granulosus(E. granulosus) infection. Methods: In vitro scolicidal activity of EEP was investi...Objective: To evaluate the in vitro and in vivo effect of the Algerian propolis ethanolic extract(EEP) against Echinococcus granulosus(E. granulosus) infection. Methods: In vitro scolicidal activity of EEP was investigated on the protoscolices of hydatid cyst. This in vitro study was conducted by using an in vivo assay. BALB/c mice were inoculated with E. granulosus and treated with propolis for three months. Hydatid cysts development was assessed. Nitric oxide(NO), tumor necrosis factor alpha(TNF-α) production and inducible NO synthase, NF-κB, and TNF-α spleen expression were estimated by Griess method and immunofluorescence respectively.Results: Our study revealed that EEP has a high scolicidal activity against E. granulosus. Oral administration of EEP decreased TNF-α, NF-κB and inducible NO synthase expression in the spleen tissues in the CE+EEP group, in comparison with the CE group. Concomitantly, EEP treatment caused an important systemic decrease in NO and TNF-α levels. These findings are associated with the reduction of CE development. Conclusions: This is the first report demonstrating with interest the antihydatic and immunomodulatory effects of the Algerian EEP, suggesting its therapeutic potential for the hydatid disease treatment.展开更多
Objective:To evaluate the scolicidal and immunomodulatory effect of the Ziziphora tenuior(Z.tenuior)extract and its fractions.Methods:Protoscolices were treated with six concentrations(3,5,10,25,50,and 100 mg/mL)of Z....Objective:To evaluate the scolicidal and immunomodulatory effect of the Ziziphora tenuior(Z.tenuior)extract and its fractions.Methods:Protoscolices were treated with six concentrations(3,5,10,25,50,and 100 mg/mL)of Z.tenuior extract and its fractions(ethanol,petroleum ether,ethyl acetate and chloroform)in periods of 10,20,30,40,50 and 60 minutes,and viability of protoscolices was evaluated using the 1.0%eosin.To examine the immunomodulatory effects of Ziziphora and its fractions on macrophage cells,the non-toxic concentration of extract and different fractions determined by MTT assay,and the Griess reaction was used to measure the level of nitrite as an indicator of nitric oxide by the macrophage cells in 10,100 and 200μg/mL in 24 hours at 37℃.Results:In this study,the Z.tenuior extract at 10 mg/mL concentration was able to kill all protoscolices during 20 minutes.By increasing the concentration to 25 mg/mL,the scolicidal time reduced to 10 minutes.Regarding the effect of different fractions of Z.tenuior,the ethanolic fraction showed the highest scolicidal activity.The extract demonstrated an inhibitory effect on the activity of macrophages and reduced nitric oxide production.Although the petroleum ether and ethanolic fractions of the extract reduced nitric oxide production,nevertheless,this effect was only significant at 10 and 100 ug/mL concentrations(P<0.05).Conclusion:The Z.tenuior extract and its fractions were effective against protoscolices yet the effect of total extract was considerable.Our findings indicates that the extract and its ethanolic and petroleum ether fractions could have anti-inflammatory properties.展开更多
Objective:To investigate the effects of 20 methanolic extracts from Malaysian selected plants on CD18/11 a expression and phagocytosis activity of leukocytes using flow cytometry analysis.Methods:The effects of methan...Objective:To investigate the effects of 20 methanolic extracts from Malaysian selected plants on CD18/11 a expression and phagocytosis activity of leukocytes using flow cytometry analysis.Methods:The effects of methanolic extracts on CD18/11 a expression and phagocytosis of leukocytes were measured by labelling the cells with CD18-fluorescein isolhiocyanaie and ingestion labelled with Escherichia coli-fluorescein isothiocyanate and then analyzed using flow cytometer.Results:About 12 out of 20 methanolic extracts of selected Malaysian medicinal plants significantly(P≤0.05) inhibited the CD18/1 la expression of leukocytes at both concentrations of 6.25 μg/mL and 100 μg/mL in dose dependent manner.The most active inhibitory was shown in Citrus aurantifolia(Christm.) Swingle and Alpinia galangal(L.) Willd.at dosage 100ug/mL.Moreover,the Orthosiphon aristatus(Blume) Miq(O.aristatus).showed the highest stimulatory activity at the concentration of 100 μg/mL.Other than that,four plant extracts significantly(P<0.05) rose the phagocytosis activities of leukocytes in dose dependent manner.However,Annona muricata L.and O.aristatus showed the highest stimulated activities at the 100 pg/mL concentration.Conclusions:The results suggest that methanolic extracts of Cirrus aurantifolia.Alpinia gaiangal,O.aristatus and Annona muricata are able to modulate innate immune system and can potentially be recognized as therapeutic agents for modulating immune system.展开更多
基金Supported by the National Natural Science Foundation of China,No.82072537the General Project of Hunan Natural Science Foundation,No.2022JJ30412 and No.2021JJ30464.
文摘Exosomes(Exos)are extracellular vesicles secreted by cells and serve as crucial mediators of intercellular communication.They play a pivotal role in the pathogenesis and progression of various diseases and offer promising avenues for therapeutic interventions.Exos derived from mesenchymal stem cells(MSCs)have significant immunomodulatory properties.They effectively regulate immune responses by modulating both innate and adaptive immunity.These Exos can inhibit excessive inflammatory responses and promote tissue repair.Moreover,they participate in antigen presentation,which is essential for activating immune responses.The cargo of these Exos,including ligands,proteins,and microRNAs,can suppress T cell activity or enhance the population of immunosuppressive cells to dampen the immune response.By inhibiting lymphocyte proliferation,acting on macrophages,and increasing the population of regulatory T cells,these Exos contribute to maintaining immune and metabolic homeostasis.Furthermore,they can activate immune-related signaling pathways or serve as vehicles to deliver microRNAs and other bioactive substances to target tumor cells,which holds potential for immunotherapy applications.Given the immense therapeutic potential of MSC-derived Exos,this review comprehensively explores their mechanisms of immune regulation and therapeutic applications in areas such as infection control,tumor suppression,and autoimmune disease management.This article aims to provide valuable insights into the mechanisms behind the actions of MSC-derived Exos,offering theoretical references for their future clinical utilization as cell-free drug preparations.
基金co-financed by the International Science&Technology Cooperation Program of Hainan Province(GHYF2023009)Jiangsu Provincial Key Research and Development Program(BE2022325)+1 种基金Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX23_0777)Qing Lan Project of Jiangsu Province and Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)。
文摘The surface macromolecules of probiotic bacteria play crucial roles in modulating immune responses in the host.Exopolysaccharide(EPS)from lactic acid bacteria(LAB)have been widely reported to exhibit immunomodulatory activity.In this study,the EPS biosynthesis gene cluster of Lacticaseibacillus paracasei S-NB was analyzed and a deletion mutant S-NBΔ7576(two genes S-NB_2175/wze and S-NB_2176/wzd were responsible for the chain length determination and export of EPS)was successfully constructed,resulting a 40.02%decrease in the production of EPS.The deletion of wze and wzd had little effect on the monosaccharide composition and major groups of the two EPS fractions(BEPS1 and BEPS2).Both BEPS1 and BEPS2 could inhibit the transcriptional level of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),inducible nitric oxide synthase(i NOS)and cyclooxygenase-2(COX-2)mRNA in RAW 264.7 cells induced by lipopolysaccharide(LPS),and enhance host immune tolerance via suppressing NF-κB and MAPK signaling.Notably,the S-NBΔ7576 mutant supplied with the BEPS1/BEPS2 exhibited more significant inhibition of cytokines production and the phosphorylation of p65 and c-Jun N-terminal kinase(JNK)in LPS-stimulated cells compared with the S-NBΔ7576 mutant alone.Our study provided the immunomodulatory effect of BEPS1 and BEPS2 from L.paracasei S-NB,in which the wze and wzd genes associated with EPS biosynthesis may play an important role.
基金the financial supports by the National Natural Science Foundation of China(82060594)the Natural Science Foundation of Jiangxi Province,China(20202BAB205006)。
文摘The biological activity of plant polysaccharides can be enhanced by sulfated modification.In this study,the immunomodulatory effect of sulfated Cyclocarya paliurus polysaccharides(SCP3)on macrophages RAW264.7 and its potential molecular mechanism were investigated.Results showed that SCP3 at 25-100μg/m L increased viability and improved phagocytosis of RAW264.7 cells.Meanwhile,SCP3 could activate mitogen-activated protein kinase(MAPK)and nuclear factor kappa B(NF-κB)signaling pathways,which increased the phosphorylation of Erk1/2,JNK,p38 and NF-κB p65,promoting secretion of cytokines tumor necrosis factorα(TNF-α),interleukin 6(IL-6)and nitric oxide(NO)as well as the production of reactive oxygen species(ROS).In addition,Toll-like receptor 4(TLR4)receptor inhibitors were able to block the production of NO and TNF-αby SCP3-stimulated macrophages.Based on Western blot analysis and validation using specific inhibitors against MAPK and NF-κB signaling pathways,the results demonstrated that SCP3 induced macrophages activation and enhanced TNF-αand NO production via TLR4-mediated MAPK and NF-κB pathways.In summary,SCP3 has significant immunomodulatory potential.The underlying molecular mechanism was that SCP3 activates macrophages via TLR4 receptors to promote ROS production,which in turn activates the downstream MAPK/NF-κB signaling pathway and then increases the secretion levels of cytokines and NO.
基金supported by Grants-in-Aid for Scientific Research(A)(19H00965,23H00354 HK)Grant-in-Aid for Scientific Research(B)(23H02358,KN)+4 种基金Grant-in-Aid for Research Activity Start-up(23K19327,FN)Challenging Research(Exploratory,23K18072,HK)JSPS Fellows(22F22080,HK)from the Japan Society for the Promotion of Science(JSPS)supported by the Research Program on Development of Innovative Technology Grants(JPJ007097)from the Project of the Bio-Oriented Technology Research Advancement Institution(BRAIN)and by the Japan Racing Association to HKsupported by the JSPS Core-to-Core Program,A.Advanced Research Networks,titled Establishment of the International Agricultural Immunology Research Core for Quantum Improvement in Food Safety。
文摘Diarrhea is a common enteric disease in piglets that leads to high mortality and economic losses in swine production worldwide.Antibiotics are commonly used to prevent or treat diarrhea in piglets.However,irrational antibiotic use contributes to the development of resistance in bacteria and antibiotic residues in animal products,threatening public health,while causing gut microbiota dysbiosis and antibiotic-resistant bacterial infection in piglets.Therefore,the quest for alternative products(such as probiotics,prebiotics,organic acids,enzymes;essential oils,medium-chain fatty acids,zinc,and plant extracts)has recently been clearly emphasized through the increase in regulations regarding antibiotic use in livestock production.These antibiotic alternatives could lower the risk of antibiotic-resistant bacteria and meet consumer demand for antibiotic-free food.Several antibiotic alternatives have been proposed,including immunomodulatory probiotics,as candidates to reduce the need for antimicrobial therapy.Many studies have revealed that probiotics can avert and cure bacterial diarrhea by regulating the gut function and immune system of piglets.In this review,we focus on the major pathogenic bacteria causing piglet diarrhear the research sta of using probiotics to prevent and treat diarrhea,their possible mechanisms,and the safety issues related to the use of probiotics.Supplementation with probiotics is a possible alternative to antibiotics for the prevention or treatment of bacterial diarrhea in piglets.Furthermore,probiotics exe rt beneficial effects on feed efficiency and growth performance of piglets.Therefore,appropriate selection and strategies for the use of probiotics may have a positive effect on growth performance and also reduce diarrhea in piglets.This review provides useful information on probiotics for researchers,pig nutritionists,and the additive industry to support their use against bacterial,diarrhea in piglets.
基金This research was financially supported by Major Public Welfare Projects in Henan Province(201300110200)National Key R&D Program of China(2018YFD0400200)+2 种基金Key scientific and technological key projects of Henan science and Technology Department(192102110214 and 202102110283)Henan Province Industry-University-Research Cooperation Project(182107000033)the special fund project of Zhengzhou basic and applied basic research(ZZSZX202003).
文摘The polysaccharides from edible fungus showed many kinds of biological activities,including anti-tumor,immunomodulatory,anti-inflammatory,anti-diabetes,improving functional constipation activities.In particular,the immunomodulatory effects have been paid more and more attention by scholars,but there was no systematic introduction of their immunomodulatory mechanism.So,this review introduced the immunomodulatory effects and mechanism of edible fungus polysaccharides in recent years,and then the relationships between structure and immunomodulatory effect were also discussed.
基金supported by Key Projects in National Science&Technology Pillar Program during the 12th Five-Year Plan Period(No.2012BAD33B04)Quality of Commodity Grain and Oil Resources and Processing Database Research–Grains(No.201313006)+5 种基金Key Projects of Tianjin Natural Science Foundation(No.13JCZDJC29800)863 National Plan(No.2012 AA022108)Agricultural Science and Technology Transformation Fund(No.2012GB2A100016)Plan for the Development of Changjiang Scholars and Innovative Research Team(No.IRT1166)National Nature Science Foundation of China(Nos.31000768 and 31171731)Tianjin Science and Technology Support Plan(No.10ZCZDSY 07000)
文摘The present study was designed to evaluate the immune-modulating effects of the polysaccharide from Grifola frondosa(GFP) by using mouse peritoneal macrophage and cytoxan(CTX) induced immunosuppression models. Our results from the phagocytotic and mononuclear phagocytic system function assays showed that GFP-A(one component from GFP) stimulated the phagocytosis of the phagocytes. The splenocyte proliferation assay showed that GFP-A acted the effect combing Con A or LPS in splenocyte proliferation. The results showed that GFP-A increased indices of thymus and spleen, the levels of LDH and ACP in the spleen, the m RNA levels of IL-1β, IL-2, IL-6 and IFN-γ in splenocyte. And GFP-A also significantly increased the expression of CD4^+ and CD8^+ splenic T lymphocytes, which were suppressed by the CTX in peripheral blood. In conclusion, our results indicate that the GFP-A is involved in immunomodulatory effects leading to its modulatory effects on immunosuppression.
基金Supported by National Natural Science Foundation of China,No.81170384
文摘It is currently difficult for conventional treatments of acute pancreatitis (AP), which primarily consist of anti-inflammatory therapies, to prevent the progression of AP or to improve its outcome. This may be because the occurrence and progression of AP, which involves various inflammatory cells and cytokines, includes a series of complex immune events. Considering the complex immune system alterations during the course of AP, it is necessary to monitor the indicators related to immune cells and inflammatory mediators and to develop more individualized interventions for AP patients using immunomodulatory therapy. This review discusses the recent advances in immunomodulatory therapies. It has been suggested that overactive inflammatory responses should be inhibited and excessive immunosuppression should be avoided in the early stages of AP. The optimal duration of anti-inflammatory therapy may be shorter than previously expected (< 24 h), and appropriate immunostimulatory therapies should be administered during the period from the 3rd d to the 14th d in the course of AP. A combination therapy of anti-inflammatory and immune-stimulating drugs would hopefully constitute an alternative to anti-inflammatory drug monotherapy. Additionally, the detection of the genotypes of critical inflammatory mediators may be useful for screening populations of AP patients at high risk of severe infections to enable the administration of early interventions to improve their prognosis. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.
文摘The most common age-related neurodegenerative disease is Alzheimer's disease(AD) characterized by aggregated amyloid-β(Aβ) peptides in extracellular plaques and aggregated hyperphosphorylated tau protein in intraneuronal neurofibrillary tangles,together with loss of cholinergic neurons,synaptic alterations,and chronic inflammation within the brain.These lead to progressive impairment of cognitive function.There is evidence of innate immune activation in AD with microgliosis.Classically-activated microglia(M1 state) secrete inflammatory and neurotoxic mediators,and peripheral immune cells are recruited to inflammation sites in the brain.The few drugs approved by the US FDA for the treatment of AD improve symptoms but do not change the course of disease progression and may cause some undesirable effects.Translation of active and passive immunotherapy targeting Aβ in AD animal model trials had limited success in clinical trials.Treatment with immunomodulatory/anti-inflammatory agents early in the disease process,while not preventive,is able to inhibit the inflammatory consequences of both Aβ and tau aggregation.The studies described in this review have identified several agents with immunomodulatory properties that alleviated AD pathology and cognitive impairment in animal models of AD.The majority of the animal studies reviewed had used transgenic models of early-onset AD.More effort needs to be given to creat models of late-onset AD.The effects of a combinational therapy involving two or more of the tested pharmaceutical agents,or one of these agents given in conjunction with one of the cell-based therapies,in an aged animal model of AD would warrant investigation.
文摘Parkinson’s disease（PD） is an age-related neurodegenerative disease for which the characteristic motor symptoms emerge after an extensive loss of dopamine containing neurons.The cell bodies of these neurons are present in the substantia nigra,with the nerve terminals being in the striatum.Both innate and adaptive immune responses may contribute to dopaminergic neurodegeneration and disease progression is potentially linked to these.Studies in the last twenty years have indicated an important role for neuroinflammation in PD through degeneration of the nigrostriatal dopaminergic pathway.Characteristic of neuroinflammation is the activation of brain glial cells,principally microglia and astrocytes that release various soluble factors.Many of these factors are proinflammatory and neurotoxic and harmful to nigral dopaminergic neurons.Recent studies have identified several different agents with immunomodulatory properties that protected dopaminergic neurons from degeneration and death in animal models of PD.All of the agents were effective in reducing the motor deficit and alleviating dopaminergic neurotoxicity and,when measured,preventing the decrease of dopamine upon being administered therapeutically after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,6-hydroxydopamine,rotenone-lesioning or delivery of adeno-associated virus-α-synuclein to the ventral midbrain of animals.Some of these agents were shown to exert an anti-inflammatory action,decrease oxidative stress,and reduce lipid peroxidation products.Activation of microglia and astrocytes was also decreased,as well as infiltration of T cells into the substantia nigra.Pretreatment with fingolimod,tanshinoine I,dimethyl fumarate,thalidomide,or cocaine-and amphetamine-regulated transcript peptide as a preventive strategy ameliorated motor deficits and nigral dopaminergic neurotoxicity in brain-lesioned animals.Immunomodulatory agents could be used to treat patients with early clinical signs of the disease or potentially even prior to disease onset in those identified as having pre-disposing risk,including genetic factors.
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financially supported by Goverment of India(grant No.SR/FT/LS-0083/2008)
文摘Objective:To explore the immunomodulatory properties of 80% ethanol extract and butanol fraction of Gentiana olivieri(G. olivieri) Griseb on Balb/C mice.Methods:The study was performed with basic models of immunomodulation such as the humoral antibody response(hemoglutination antibody titres), cell mediated immune response(delayed type hypersensitivity and in vivocarbon clearance or phagocytosis). Ethanol(80%) extract of flowering aerial parts of G.olivieriand its butanol fraction were administered p.o.(orally) to the mice. Levamisole, 2.5 mg/kg was used as standard drug.Results:There was a potentiation of immune response to sheep red blood cells by cellular and humoral mediated mechanisms comparable to levamisole(2.5 mg/kg) by both 80% ethanol extract and the butanol fraction at doses of 50-200 mg/kg in male Balb/C mice. Both significantly(P<0.01) potentiated the humoral immune response in cyclophosphamide(250 mg/kg)immunosupressed mice at 100 and 200 mg/kg of each extract and fraction as compared to control.The potentiation of delayed type hypersensitivity response was statistically significant(P<0.01) at200 mg/kg of ethanol extract and 100, 200 mg/kg of butanol fraction as compared to control. The phagocytosis was significant at 200 mg/kg with butanol fraction ofG. olivieri.Conclusions:The results reveal the immunostimulant effects of plantG. olivieriin mice by acting through cellular and humoral immunity in experimental models of immunity in mice. Butanol fraction is the most effective at a dose level of 200 mg/kg.
基金supported by the National Natural Science Foundation of China(No.30572314)the Basic Research Program of Science and Technology,Ministry of Science and Technology of China(No.2007FY210500)+1 种基金the Program of Chinese Offshore Investigation and Assessment,State Oceanic Administration of China(Nos.908-01-ST12,908-02-05-04)Science and Technology Program of Shandong Province,China(No.03BS109)
文摘Seaweed Complex Preparation （SCP） is a clinical traditional Chinese medicine preparation which is composed of seven traditional Chinese herbs, and it has been used for treatment of lung cancer, liver cancer and digestive cancer. However, little infor- mation is available about the pharmacodynamic basis. The antitumor, immunomodulatory and free radical scavenging effects of SCP were evaluated in this study. Transplanted tumor in vivo method was used to determine the antitumor effect. The effects on spleno- cyte proliferation and phagocytosis of macrophages in tumor-bearing mice were measured by the MTT method and the phagocytizing cock red blood cell （CRBC） method respectively. The scavenging activities of SCP on DPPH and hydroxyl radicals in vitro were investigated. It was found that the medium-dose and high-dose of SCP could significantly inhibit the growth of transplanted hepatic tumor of murine hepatocarcinoma cell line H22, and promote proliferation of splenocytes and phagocytosis of macrophages. SCP possessed noticeable scavenging activities on DPPH and hydroxyl radicals. The antiturnor effects of SCP might be achieved by im- proving immune system and scavenging free radicals, which is in accordance with the viewpoint of traditional Chinese medicine in promoting the body resistance and eliminating pathogenic factors for cancer treatment.
文摘Objective:In our continued efforts to isolate the active immunomodulatory and antiviral constituents of Loranthus micranthus Linn parasitic on Kola acuminata,we set out to fractionate the crude aqueous methanol extract of the plant.The establishment of the most potent fraction(s) as well as the isolation of the pure active secondary metabolite responsible for the immune stimulatory and antiviral activities in Eastern Nigeria mistletoe has become very needful.This will enable us prove our assumption that this particular specie is different from the European version,Viscum album.Methods:Five solvents of varying polarity namely n-hexane,chloroform, ethylacetate,acetone and methanol were successively employed in the complete fractionation of the crude aqueous -methanol extract of Eastern Nigerian mistletoe,Loranthus micranthus Linn.,harvested from Kola acuminata in that order.The fractions were dried in-vacuo using a rotary evaporator maintained at a temperature of(40±5)℃.The different fractions were screened for immunomodulatory activity using a universal model:the cellular - mediated delayed type hypersensivity test in experimental mice.This was performed by administering two different dose levels:250 mg/kg and 500 mg/kg of each fraction against standard positive and negative control. Results:Results of the study established dose-dependent immunostimulatory(upregulatory) effects of the five fractions of the extract as the model used in the study with different percentage stimulations compared to controls.At the dose levels of 500 mg/kg and 250 mg/kg body weight,the percentage stimulation observed were as following:chloroform fraction 311.11%and 122.22%,ethyl acetate fraction 193.38%and 95. 56%,n-hexane 155.56%and 3.50%,acetone fraction 95.56%and 51.11%and methanol fraction 68. 89%and 24.44%respectively.Levamisole,a known potent immunostimulant,afforded a stimulation of 68. 89%at a dose of 2.5 mg/kg.Conclusion:The study showed that the order of immunomodulatory potency is chloroform fraction > ethylacetate fraction > hexane fraction > acetone fraction > methanol fraction.Bioassayguided fractionation and purification of the active extracts led to the isolation of pure compounds phytochemically characterized as sterols and flavonoids.This work indicates that the main constituents of our local mistletoe responsible for immunostimulation are the flavonoids,terpenoids and or steroids.Glycosides,carbohydrates, tannins and alkaoids appear to augment the measured activities.
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.
基金Supported by (in part) A grant from Catalysis Laboratories,Spain
文摘AIM:To investigate the efficacy of Viusid,a nutritional supplement,as an antioxidant and an immunomodulator in patients with chronic hepatitis C.METHODS:Sixty patients with chronic hepatitis C who were non-responders to standard antiviral treatment were randomly assigned to receive Viusid(3 sachets daily,n=30) or placebo(n=30) for 24 wk.The primary outcome was the change in serum malondialdehyde and 4-hydroxyalkenals(lipid peroxidation products).Secondary outcomes were changes in serum tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ) and interleukin-10(IL-10).RESULTS:Statistically significant reductions in serum 4-hydroxyalkenals and malondialdehyde levels were observed in both groups in comparison with pretreatment values,but the patients who received Viusid showed a more marked reduction as compared with the control group(P=0.001).TNF-α levels significantly increased from 6.9 to 16.2 pg/mL(P< 0.01) in the patients who received placebo in comparison with almost unchanged levels,from 6.6 to 7.1 pg/mL(P=0.26),in the patients treated with Viusid(P=0.001).In addition,IL-10 levels were markedly increased in the patients treated with Viusid(from 2.6 to 8.3 pg/mL,P=0.04) in contrast to the patients assigned to placebo(from 2.8 to 4.1 pg/mL,P=0.09)(P=0.01).Likewise,the administration of Viusid markedly increased mean IFN-γ levels from 1.92 to 2.89 pg/mL(P< 0.001) in comparison with a reduction in mean levels from 1.80 to 1.68 pg/mL(P=0.70) in the placebo group(P< 0.0001).Viusid administration was well tolerated.CONCLUSION:Our results indicate that treatment with Viusid leads to a notable improvement of oxidative stress and immunological parameters in patients with chronic hepatitis C.
基金Education Department of Jilin Province(No.JJKH20201177KJ)the Foundation of Department of Human Resources and Social Security of Jilin Province(No.2020009)the Foundation of Jilin Province Development and Reform Commission(No.2020C015).
文摘Crassostrea sikamea(C.sikamea)is an important edible and medicinal seafood in China.In the present study,a compound named flazin was separated and identified from the ethyl acetate extract of C.sikamea(EAECs)for the first time.In addition,the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetra zolium(MTS)assay revealed that EAECs and flazin inhibited the transformation of splenic lymphocytes in vitro.Moreover,flazin(20μg·mL^(−1))altered the populations of splenic lymphocyte subtypes.Real-time quantitative PCR(RT-qPCR)analysis and enzyme-linked immunosorbent assay(ELISA)showed that flazin suppressed the mRNA expression and secretion of TNF-αand IL-2,and reversed Concanavalin A(ConA)-induced mRNA up-regulation and protein secretion of TNF-αand IL-2.Western blot results showed that flazin reversed ConA-induced increases in p-ERK1/2 and p-p38 in splenocytes.In conclusion,flazin exhibits effective immunomodulatory function and may be useful for treating immune-related disorders,which indicates the application potential of C.sikamea as a functional food or immunomodulator.
文摘Huang Qi(黄芪Astragalus membranaceus)is a well-known and widely used herb in traditional Chinese medicine(TCM)tonic preparations.It has been used for many ailments over the last 2000 years.Flavonoids,saponins,and polysaccharides have been shown to be the main compounds responsible for the biological and pharmacological activities,especially the immunomodulatory properties,of such tonic preparations.This review summarizes the published data on Astragalus extracts and fractions and the natural compounds responsible for the immunomodulatory activity with special reference to the modulation of nuclear factor-kappa B and related pathways(e.g.,Nrf2).In addition,this review highlights the importance of Astragalus membranaceus in TCM for treating patients with diseases related to immunocompromised conditions,such as cancer and diabetes.
基金financially supported by Research Agency in Health Sciences ATRSS(N.59/DFPR/ATRSS)
文摘Objective: To evaluate the in vitro and in vivo effect of the Algerian propolis ethanolic extract(EEP) against Echinococcus granulosus(E. granulosus) infection. Methods: In vitro scolicidal activity of EEP was investigated on the protoscolices of hydatid cyst. This in vitro study was conducted by using an in vivo assay. BALB/c mice were inoculated with E. granulosus and treated with propolis for three months. Hydatid cysts development was assessed. Nitric oxide(NO), tumor necrosis factor alpha(TNF-α) production and inducible NO synthase, NF-κB, and TNF-α spleen expression were estimated by Griess method and immunofluorescence respectively.Results: Our study revealed that EEP has a high scolicidal activity against E. granulosus. Oral administration of EEP decreased TNF-α, NF-κB and inducible NO synthase expression in the spleen tissues in the CE+EEP group, in comparison with the CE group. Concomitantly, EEP treatment caused an important systemic decrease in NO and TNF-α levels. These findings are associated with the reduction of CE development. Conclusions: This is the first report demonstrating with interest the antihydatic and immunomodulatory effects of the Algerian EEP, suggesting its therapeutic potential for the hydatid disease treatment.
基金the Research Division of Qazvin University of Medical Sciences for supporting the project financiallythe Medicinal Plants Research Center,Institute of Medicinal Plants,(ACECR),Karaj,Iran
文摘Objective:To evaluate the scolicidal and immunomodulatory effect of the Ziziphora tenuior(Z.tenuior)extract and its fractions.Methods:Protoscolices were treated with six concentrations(3,5,10,25,50,and 100 mg/mL)of Z.tenuior extract and its fractions(ethanol,petroleum ether,ethyl acetate and chloroform)in periods of 10,20,30,40,50 and 60 minutes,and viability of protoscolices was evaluated using the 1.0%eosin.To examine the immunomodulatory effects of Ziziphora and its fractions on macrophage cells,the non-toxic concentration of extract and different fractions determined by MTT assay,and the Griess reaction was used to measure the level of nitrite as an indicator of nitric oxide by the macrophage cells in 10,100 and 200μg/mL in 24 hours at 37℃.Results:In this study,the Z.tenuior extract at 10 mg/mL concentration was able to kill all protoscolices during 20 minutes.By increasing the concentration to 25 mg/mL,the scolicidal time reduced to 10 minutes.Regarding the effect of different fractions of Z.tenuior,the ethanolic fraction showed the highest scolicidal activity.The extract demonstrated an inhibitory effect on the activity of macrophages and reduced nitric oxide production.Although the petroleum ether and ethanolic fractions of the extract reduced nitric oxide production,nevertheless,this effect was only significant at 10 and 100 ug/mL concentrations(P<0.05).Conclusion:The Z.tenuior extract and its fractions were effective against protoscolices yet the effect of total extract was considerable.Our findings indicates that the extract and its ethanolic and petroleum ether fractions could have anti-inflammatory properties.
基金Supported by Ministry of Higher Education.Malaysia(Grant No.GUP-SK-07-23-042)
文摘Objective:To investigate the effects of 20 methanolic extracts from Malaysian selected plants on CD18/11 a expression and phagocytosis activity of leukocytes using flow cytometry analysis.Methods:The effects of methanolic extracts on CD18/11 a expression and phagocytosis of leukocytes were measured by labelling the cells with CD18-fluorescein isolhiocyanaie and ingestion labelled with Escherichia coli-fluorescein isothiocyanate and then analyzed using flow cytometer.Results:About 12 out of 20 methanolic extracts of selected Malaysian medicinal plants significantly(P≤0.05) inhibited the CD18/1 la expression of leukocytes at both concentrations of 6.25 μg/mL and 100 μg/mL in dose dependent manner.The most active inhibitory was shown in Citrus aurantifolia(Christm.) Swingle and Alpinia galangal(L.) Willd.at dosage 100ug/mL.Moreover,the Orthosiphon aristatus(Blume) Miq(O.aristatus).showed the highest stimulatory activity at the concentration of 100 μg/mL.Other than that,four plant extracts significantly(P<0.05) rose the phagocytosis activities of leukocytes in dose dependent manner.However,Annona muricata L.and O.aristatus showed the highest stimulated activities at the 100 pg/mL concentration.Conclusions:The results suggest that methanolic extracts of Cirrus aurantifolia.Alpinia gaiangal,O.aristatus and Annona muricata are able to modulate innate immune system and can potentially be recognized as therapeutic agents for modulating immune system.
