Parkinson’s disease(PD)is a common neurodegenerative disorder with no cure.Astragalus membranaceus is used in Chinese culture as a food supplement to boost immunity.The present study aimed to explore the neuroprotect...Parkinson’s disease(PD)is a common neurodegenerative disorder with no cure.Astragalus membranaceus is used in Chinese culture as a food supplement to boost immunity.The present study aimed to explore the neuroprotective effects of total flavonoids extracted from A.membranaceus(TFA)and their protective mechanisms.TFA offered neuroprotection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)in the mouse model of Parkinsonism,by improving behavior performance in the gait analysis and pole test,and inhibiting the decline of tyrosine hydroxylase(TH)positive neurons and TH protein expression in substantia nigra of mice.TFA also prevented 1-methyl-4-phenylpyridinium(MPP+)induced neurotoxicity in SHSY5Y cells,by increasing GSH and GSH/GSSG ratio,and reducing reactive oxygen species.In addition,the neuroprotective effects of TFA were associated with its ability to restore MPTP/MPP+induced downregulation of SLC7A11 and glutathione peroxidase 4(GPX-4).In conclusion,we demonstrated that TFA exerted significant neuroprotection against MPTP/MPP+induced neurodegeneration by inhibiting ferroptosis through the regulation of SLC7A11/GPX-4 axis,suggesting the use of TFA as a possible food supplement in the prevention of PD.展开更多
[Objectives]This study was conducted to investigate the effects of Astragalus membranaceus in different groups on energy metabolism and CNTF protein expression in skeletal muscle of exercise-induced fatigue rats.[Meth...[Objectives]This study was conducted to investigate the effects of Astragalus membranaceus in different groups on energy metabolism and CNTF protein expression in skeletal muscle of exercise-induced fatigue rats.[Methods]Thirty-five clean male SD rats were randomly divided into a normal group,and low-,meddle-and high-dose groups of A.membranaceus aqueous solution,with 7 rats in each group.The low-dose,medium-dose and high-dose groups were given by gavage at 0.65,1.3 and 2.6 g/kg,respectively,while the normal group and the model group were given normal food and water.The weight of rats was observed.The contents of serum urea,lactate,muscle glycogen,liver glycogen and CNTF expression were detected.[Results]After modeling,compared with the normal group,the serum lactate and urea contents of rats in the model group significantly increased(P<0.01),while the muscle glycogen content(P<0.01)and liver glycogen content(P<0.05)of the skeletal muscle significantly decreased.Compared with the model group,the low-,meddle-and high-dose groups of A.membranaceus significantly reduced the levels of lactate and urea in serum(P<0.01),while the levels of muscle glycogen and liver glycogen in the skeletal muscle significantly increased(P<0.01,P<0.05).[Conclusions]This study provides a good research foundation for the treatment of exercise-induced fatigue using traditional Chinese herb A.membranaceus in modern clinical practice.展开更多
As a traditional Chinese medicine,the root of Astragalus membranaceus var.mongholicus(AMM)or A.membranaceus(AM)has been widely used in China and other Asian countries for thousands of years.Till now,the flavonoids,phe...As a traditional Chinese medicine,the root of Astragalus membranaceus var.mongholicus(AMM)or A.membranaceus(AM)has been widely used in China and other Asian countries for thousands of years.Till now,the flavonoids,phenolic acids and saponins are considered as the main active components contributing to their therapeutic effect in these plants.In order to clarify the distribution and contents of these compounds in different organs of these plants,a rapid and sensitive analytical method for simultaneous determination of 25 active compounds including seven types(i.e.dihydroflavones,isoflavane,isoflavones,flavones,pterocarpans,phenolic acid and saponins)within 10 min was established using ultra-pressure liquid chromatography coupled with tandem mass spectrometry(UPLCeMS/MS).Then,the established method was fully validated and successfully applied to the determination of the contents of these analytes in different parts(root,rhizome,stem,leaf and flower)of AMM and AM.The results indicated that the contents of the same type of compounds in two different species plants were significantly different.Moreover,the obvious differences were also found for the distribution and contents of different type of compounds in five organs of the same species.The present study could provide necessary information for the rational development and utilization of AMM and AM resource.展开更多
A new isoflavane named astraganoside,together with five known compounds had been isolated from the processed Astragralus membranaceus.The structure of the novel compound was elucidated as(3R,4R)-3-(2-hydroxy-3,4-dimet...A new isoflavane named astraganoside,together with five known compounds had been isolated from the processed Astragralus membranaceus.The structure of the novel compound was elucidated as(3R,4R)-3-(2-hydroxy-3,4-dimethoxyphenyl)chroman- 4,7-diol-7-O-β-D-glucopyranoside(1)based on spectroscopic methods including UV,IR,ESI-MS,1D NMR and 2D NMR techniques.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 explore the anti-cancer mechanism of active ingredients of Astragalus membranaceus (AM) through network pharmacology. Methods: TCMSP, PubChem, STICTH and GeneCards databases were used to predict and scre...Objective: To explore the anti-cancer mechanism of active ingredients of Astragalus membranaceus (AM) through network pharmacology. Methods: TCMSP, PubChem, STICTH and GeneCards databases were used to predict and screen the main active ingredients and anti-cancer targets of AM. Active ingredient-target-disease network was constructed by Cytoscape 3.7.0 software, and protein interaction network was constructed by STRING platform. KEGG signaling pathway and GO biological process of targets were analyzed by Bioconductor database. Results: Twenty-four active ingredients were screened from AM, which acted on 106 cancer targets such as PTGS, NCOA2, ADRB2, PRSS1, NOS2, NOS3, GABRA1. Through these targets, the anti-cancer effect of AM mainly acts on small cell lung cancer, colorectal cancer, thyroid cancer, breast cancer, non-small cell lung cancer, hepatocellular carcinoma, pancreatic cancer, gastric cancer, endometrial cancer, enriched in chemical carcinogenesis, Platinum drug resistance, Epstein-Barr virus infection, TNF signaling pathway, Toll-like receptor signaling pathway, p53 signaling pathway, VEGF signaling pathway, NF-kappa B signaling pathway, and PI3K - Akt signaling pathway. Conclusion: This study found that the main anti-cancer compounds of AM are kaempferol, quercetin, 7-O-methylisomucronulatol, formononetin, isorhamnetin, Calycosin, 3,9-di-O-methylnissolin. The main targets include PTGS, PTGS1, NCOA2, ADRB2, PRSS1, NOS2, NOS3, GABRA1, F2. The mechanisms involved in anticancer could be summarized as following: blocking the chemical carcinogenesis, reversing the platinum drug resistance, anti - Epstein - Barrvirus infection, and inhibiting cell proliferation related signaling pathways, such as TNF signaling pathway, Tolllike receptor signaling pathway, p53 signaling pathway, VEGF signaling pathway, NF-kappa B signaling pathway, PI3K - AKT signaling pathway.展开更多
Objective:Prostate cancer(PCa)is the second most common male malignancy tumor in the world,and the occurrence rate and the mortality of PCa keeps increasing nowadays,exploration of accurate biomarker and predict clini...Objective:Prostate cancer(PCa)is the second most common male malignancy tumor in the world,and the occurrence rate and the mortality of PCa keeps increasing nowadays,exploration of accurate biomarker and predict clinical outcome of PCa is of great significance.Traditional Chinese medicine Huangqi(Astragalus membranaceus,AM)has been widely used for PCa treatment in China,while the pharmacological mechanisms are still unclear.The current paper intend to perform a network pharmacology analysis to reveal the mechanism of the effects of AM in PCa.Methods:Traditional Chinese Medicine Systems Pharmacology Database(TCMSP)was used to obtain chemical constituents of AM.PCa-related target genes were collected via OMIM and GeneCards databases.PCa-AM common target protein interaction network was established by the STRING database.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed to further explore the PCa mechanism and therapeutic effect of AM.The network diagrams of the active component-action target and protein-protein interaction(PPI)networks were constructed using Cytoscape software.Results:A total of 20 active ingredients contained and 462 putative identified target genes were screened from AM,of which 46 overlapped with the targets of PCa and were considered potential therapeutic targets.The analysis of the network results showed that the AM activity components quercetin,kaempferol,isorhamnetin,3,9-di-O-methylnissolin and 7-O-methylisomucronulatol have a good binding activity with top ten screened targets,such as MYC,AKT1,CCND1,MAPK1,CASP3,EGFR,ESR1,VEGFA,ERBB2 and IL-6.GO and KEGG analyses revealed that these targets were associated with proteoglycans in cancer,virus infection,microRNAs in cancer,PI3K-Akt signaling pathway,and other biological process.Conclusion:This study demonstrated the multicomponent,multitarget,and multichannel characteristics of AM,which provided a novel approach for further research of the mechanism of AM in the treatment of PCa.展开更多
A new isoflavone glucoside, 3’-methoxy-5’-hydroxy-isoflavone-7-O-β-D-glucoside, was isolated from the roots of Astragalus membranaceus and its structure waselucidated by spectroscopic data.
Objective:To evaluate the mechanism of Astragalus membranaceus(AM)by intervening peritoneal mesothelial cells(PMCs),epithelial-mesenchymal transition(EMT),and spleen deficiency syndrome(SDS)in peritoneal fibrosis(PF),...Objective:To evaluate the mechanism of Astragalus membranaceus(AM)by intervening peritoneal mesothelial cells(PMCs),epithelial-mesenchymal transition(EMT),and spleen deficiency syndrome(SDS)in peritoneal fibrosis(PF),we base on employing the strategy of Q-marker theory combination network pharmacology method.Methods:First,we obtained the Q-markers of AM by searching the relevant literature and its pharmacological information was collected based on SwissADME.The SwissTargetPrediction and pharmmaper were employed to predict its potential target.Secondly,GeneCards,DisGeNET,and OMIM databases were employed to search the related targets of EMT,SDS,and PF.VENNY2.1 tool was employed to obtain the intersection targets of AM and the three;then the“AM potential target-SDS-EMT-PF”Venn diagram was constructed.The common targets of AM,EMT and SDS were uploaded to the STRING database and obtained the PPI protein interaction network map.Cytoscape 3.7.2 was employed to evaluate the core target of PPI network.PATHER and Metascape databases were used to analyze protein type,GO biological process,and KEGG pathway.Finally,a network diagram of the“TCM-component-disease target-pathway”was drawn.Results:A total of 10 AM Q-makers were screened out,corresponding to 335 targets of AM,2,728 targets of SDS,373 of EMT,and 612 PF targets were found.Among them,there are 155 common AM targets related to SDS and EMT.Key targets such as ALB,AKT1,VEGFA,TNF,EGFR,CASP3,SRC,STAT3,HSP90AA1,and ESR1 were obtained.The core drug include quercetin,astragalosideIII,Calycosin-7-O-beta-D-glucoside,astragalosideIV,etc.The types of PPI proteins include protein modification enzymes,metabolite transferases,transmembrane signal receptors,etc.Biological processes include the regulation of kinase activity,the positive regulation of transferase activity,and the regulation of kinase activity.The key pathways may include PI3K-Akt signaling pathways,the non-smad pathway of the TGF-βsignaling pathway,and the AGE-RAGE signaling pathway.Conclusion:AM could prevent and treat PF through a multi-component multi-target-multi-path mechanism.Astragalus saponins may be the main component types of AM intervening EMT pathology by strengthening the spleen and nourishing Qi.AstragalosideIV and astragalosideIII may be the constituents that can invigorate the spleen and replenish Qi.The results of this study contribute to a more comprehensive understanding of the critical components and mechanisms of AM by intervening SDS and EMT in the treatment of PF.展开更多
The primary chemical components of Astragalus membranaceus include polysaccharides,saponins,flavonoids,and amino acids.Recent studies have shown that Astragalus membranaceus has multiple functions,including improving ...The primary chemical components of Astragalus membranaceus include polysaccharides,saponins,flavonoids,and amino acids.Recent studies have shown that Astragalus membranaceus has multiple functions,including improving immune function and exerting antioxidative,anti-radiation,anti-tumor,antibacterial,antiviral,and hormone-like effects.Astragalus membranaceus and its extracts are widely used in clinical practice because they have obvious therapeutic effects against various autoimmune diseases and relatively less adverse reaction.Multiple sclerosis(MS)is an autoimmune disease of central nervous system(CNS),which mainly caused by immune disorder that leads to inflammatory demyelination,inflammatory cell infiltration,and axonal degeneration in the CNS.In this review,the authors analyzed the clinical manifestations of MS and experimental autoimmune encephalomyelitis(EAE)and focused on the efficacy of Astragalus membranaceus and its chemical components in the treatment of MS/EAE.展开更多
Astragalosides are the main active constituents of traditional Chinese medicine Huang-Qi,of which cycloastragenol-type glycosides are the most typical and major bioactive compounds.This kind of compounds exhibit vario...Astragalosides are the main active constituents of traditional Chinese medicine Huang-Qi,of which cycloastragenol-type glycosides are the most typical and major bioactive compounds.This kind of compounds exhibit various biological functions including cardiovascular protective,neuroprotective,etc.Owing to the limitations of natural sources and the difficulties encountered in chemical synthesis,re-engineering of biosynthetic machinery will offer an alternative and promising approach to producing astragalosides.However,the biosynthetic pathway for astragalosides remains elusive due to their complex structures and numerous reaction types and steps.Herein,guided by transcriptome and phylogenetic analyses,a cycloartenol synthase and four glycosyltransferases catalyzing the committed steps in the biosynthesis of such bioactive astragalosides were functionally characterized from Astragalus membranaceus.AmCAS1,the first reported cycloartenol synthase from Astragalus genus,is capable of catalyzing the formation of cycloartenol;AmUGT15,AmUGT14,AmUGT13,and AmUGT7 are four glycosyltransferases biochemically characterized to catalyze 3-O-xylosylation,3-O-glucosylation,25-O-glucosylation/O-xylosylation and 2’-O-glucosylation of cycloastragenol glycosides,respectively.These findings not only clarified the crucial enzymes for the biosynthesis and the molecular basis for the structural diversity of astragalosides in Astragalus plants,also paved the way for further completely deciphering the biosynthetic pathway and constructing an artificial pathway for their efficient production.展开更多
The water-based foam stabilized by the natural surfactant applied in the fabrication of porous materials has attracted extensive attention,as the advantages of cleanness,convenience and low cost.Particularly,the devel...The water-based foam stabilized by the natural surfactant applied in the fabrication of porous materials has attracted extensive attention,as the advantages of cleanness,convenience and low cost.Particularly,the development of a green preparation method has became themain research focus and frontier.In thiswork,a green liquid foamwith high stability was prepared by synergistic stabilization of natural plant astragalus membranaceus(AMS)and attapulgite(APT),and then a novel porous material with sufficient hierarchical pore structure was templated from the foam via a simple free radical polymerization of acrylamide(AM).The characterization results revealed that the amphiphilic molecules from AMS adsorbed onto thewater-air interface and formed a protective shell to prevent the bubble breakup,and APT gathered in the plateau border and formed a three-dimensional network structure,which greatly slowed down the drainage rate.The porous material polyacrylamide/astragalus membranaceus/attapulgite(PAM/AMS/APT)showed the excellent adsorption performance for cationic dyes of Methyl Violet(MV)and Methylene Blue(MB)in water,and the maximum adsorption capacity could reach to 709.13 and 703.30 mg/g,respectively.Furthermore,the polymer material enabled to regenerate and cycle via a convenient calcination process,and the adsorption capacitywas still higher than 200 mg/g after five cycles.In short,this research provided a new idea for the green preparation of porous materials and the treatment of water pollution.展开更多
Astragalus membranaceus(Radix Astragali, RA) and Atractylodes macrocephala(Rhizoma Atractylodis Macrocephalae, RAM) are often used to treat gastrointestinal diseases. In the present study, we determined the effects of...Astragalus membranaceus(Radix Astragali, RA) and Atractylodes macrocephala(Rhizoma Atractylodis Macrocephalae, RAM) are often used to treat gastrointestinal diseases. In the present study, we determined the effects of polysaccharides extracts from these two herbs on IEC-6 cell migration and explored the potential underlying mechanisms. A migration model with IEC-6 cells was induced using a single-edged razor blade along the diameter of cell layers in six-well polystyrene plates. The cells were grown in control--media or media containing spermidine(5 μmol·L^(-1), SPD), alpha-difluoromethylornithine(2.5 mmol·L^(-1), DFMO), 4-Aminopyridine-(40 μ-mol·L^(-1), 4-AP), the polysaccharide extracts of RA or RAM(50, 100, or 200 mg·L^(-1)), DFMO plus SPD, or DFMO plus polysaccharide extracts of RA or RAM for 12 or 24 h. Next, cytosolic free Ca^(2+)([Ca^(2+)]cyt) was measured using laser confocal microscopy, and cellular polyamine content was quantified with HPLC. Kv1.1 mRNA expression was assessed using RT-qPCR and Kv1.1 and RhoA protein expressions were measured with Western blotting analysis. A cell migration assay was carried out using Image-Pro Plus software. In addition, GC-MS was introduced to analyze the monosaccharide composition of both polysaccharide extracts. The resutls showed that treatment with polysaccharide extracts of RA or RAM significantly increased cellular polyamine content, elevated [Ca^(2+)]cyt and accelerated migration of IEC-6 cells, compared with the controls(P < 0.01). Polysaccharide extracts not only reversed the inhibitory effects of DFMO on cellular polyamine content and [Ca^(2+)]cyt, but also restored IEC-6 cell migration to control level(P < 0.01 or < 0.05). Kv1.1 mRNA and protein expressions were increased(P < 0.05) after polysaccharide extract treatment in polyamine-deficient IEC-6 cells and RhoA protein expression was increased. Molar ratios of D-ribose, D-arabinose, L-rhamnose, D-mannose, D-glucose, and D-galactose was 1.0:14.1:0.3:19.9:181.3:6.3 in RA and 1.0:4.3:0.1:5.7:2.8:2.2 in RAM. In conclusion, treatment with RA and RAM polysaccharide extracts stimulated migration of intestinal epithelial cells via a polyamine-Kv1.1 channel activated signaling pathway, which facilitated intestinal injury healing.展开更多
Astragalus membranaceus may be a potential therapy for childhood asthma but its driving mechanism remains elusive. The main components of A. membranaceus were identified by HPLC. The children with asthma remission wer...Astragalus membranaceus may be a potential therapy for childhood asthma but its driving mechanism remains elusive. The main components of A. membranaceus were identified by HPLC. The children with asthma remission were divided into two combination group(control group, the combination of budesonide and terbutaline) and A. membranaceus group(treatment group, the combination of budesonide, terbutaline and A. membranaceus). The therapeutic results were compared between two groups after 3-month therapy.Porcine peripheral blood mononuclear cells(PBMCs) were isolated from venous blood by using density gradient centrifugation on percoll. The levels of Fox P3, EGF-β, IL-17 and IL-23 from PBMCs and serum Ig E were measured. The relative percentage of Treg/Th17 cells was determined using flow cytometry. The main components of A. membranaceus were calycosin-7-O-glucoside, isoquercitrin, ononin, calycosin, quercetin, genistein, kaempferol, isorhamnetin and formononetin, all of which may contribute to asthma therapy. Lung function was significantly improved in the treatment group when compared with a control group(P < 0.05). The efficacy in preventing the occurrence of childhood asthma was higher in the treatment group than the control group(P < 0.05).The levels of Ig E, IL-17 and IL-23 were reduced significantly in the treatment group when compared with the control group, while the levels of FoxP3 and TGF-β were increased in the treatment group when compared with the control group(P < 0.05). A. membranaceus increased the percentage of Treg cells and reduced the percentage of Th17 cells. A. membranaceus is potential natural product for improving the therapeutic efficacy of combination therapy of budesonide and terbutaline for the children with asthma remission by modulating the balance of Treg/Th17 cells.展开更多
The interaction between immune cells and hepatic stellate cells(HSCs)can modulate the development of hepatic fibrosis.It can also regulate hepatic fibrosis and liver cirrhosis caused by excessive deposition of extrace...The interaction between immune cells and hepatic stellate cells(HSCs)can modulate the development of hepatic fibrosis.It can also regulate hepatic fibrosis and liver cirrhosis caused by excessive deposition of extracellular matrix(ECM).This article reviews the action mechanism of immune cells on liver fibrosis and the effect of Astragalus membranaeus and its active components on immune cells.In-depth study of interaction between immune cells and HSCs on the pathogenesis of liver fibrosis,and the regulatory effect of Astragalus membranaeus and its active components on immune mechanism will provide new insights in the treatment of liver fibrosis.展开更多
Erythrocytes play an essential role in transporting O_2 and CO_2 for respiration in fish. However,erythrocytes continuously suffer from reactive oxygen species(ROS)-induced oxidative stress and apoptosis. Thus, it is ...Erythrocytes play an essential role in transporting O_2 and CO_2 for respiration in fish. However,erythrocytes continuously suffer from reactive oxygen species(ROS)-induced oxidative stress and apoptosis. Thus, it is essential to expand our knowledge of how to protect erythrocytes against ROS-induced oxidative stress and apoptosis in fish. In this study, we explored the cytotoxicity and the effects of butylated hydroxyanisole(BHA), ethyl ether extracts, ethyl acetate extracts, acetone extracts(AE), ethanol extracts, and aqueous extracts of Astragalus membranaceus(EAm) on hydroxyl radical(·OH)-induced apoptosis in carp erythrocytes. The rat hepatocytes and carp erythrocytes were incubated with different concentrations of BHA or EAm(0.125 to 1 mg/mL). The toxicity in rat hepatocytes and carp erythrocytes was then measured using a 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide(MTT) assay and a haemolysis assay,respectively. The carp erythrocytes were treated with BHA or EAm in the presence of 40 μmol/L FeSO4 and20 μmol/L H_2 O_2 at 37℃, except for the control group. Oxidative stress and apoptosis parameters in the carp erythrocytes were then evaluated using the commercial kit. The results indicated that at high concentrations, BHA and EAm could induce toxicity in rat hepatocytes and fish erythrocytes. However, BHA was more toxic than EAm at the same concentrations. Moreover, the toxicity order of BHA and EAm in the fish erythrocytes approximately agreed with that for the rat hepatocytes. Butylated hydroxyanisole and EAm suppressed the ·OH-induced phosphatidylserine exposure and DNA fragmentation(the biomarkers of apoptosis) by decreasing the generation of ROS, inhibiting the oxidation of cellular components, and restoring the activities of antioxidants in carp erythrocytes. Of all of the examined EAm, the AE showed the strongest effects. The effects of AE on superoxide anion, H_2 O_2, met-haemoglobin and reduced glutathione levels, as well as glutathione reductase activity and apoptosis were equivalent to or stronger than those of BHA. These results revealed that the AE of Astragalus membranaceus could be used as a potential natural antioxidant or apoptosis inhibitor in fish erythrocytes.展开更多
Astragalus membranaceus(A.membranaceus)is a widely used traditional herb in China and Korea.A.membranaceus polysaccharides(AMP),which make up a major part of the root extract,have been shown to modulate immune modulat...Astragalus membranaceus(A.membranaceus)is a widely used traditional herb in China and Korea.A.membranaceus polysaccharides(AMP),which make up a major part of the root extract,have been shown to modulate immune modulations,especially activation of bone marrow-derived dendritic cells(BMDCs)and T cells.However,the immune stimulatory effect of AMP in the mouse in vivo and human peripheral blood DCs(PBDCs)has not been well investigated.In this study,we found that intravenous(i.v.)injection of AMP in C57 BL/6 mice induced remarkable elevations in co-stimulatory and MHC class I and II molecule levels in the splenic DCs and its subsets.The stimulatory effect of DCs by AMP was elevated 6 h after treatment,which rapidly decreased 18 h after injection.Furthermore,AMP promoted intracellular production of pro-inflammatory cytokines in spleen DC subsets,which contributed elevation of serum cytokine levels.Finally,the AMP promoted PBDC activation.Thus,these results demonstrate that AMP can be used as an immune stimulatory molecules in human and mouse.展开更多
文摘Parkinson’s disease(PD)is a common neurodegenerative disorder with no cure.Astragalus membranaceus is used in Chinese culture as a food supplement to boost immunity.The present study aimed to explore the neuroprotective effects of total flavonoids extracted from A.membranaceus(TFA)and their protective mechanisms.TFA offered neuroprotection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)in the mouse model of Parkinsonism,by improving behavior performance in the gait analysis and pole test,and inhibiting the decline of tyrosine hydroxylase(TH)positive neurons and TH protein expression in substantia nigra of mice.TFA also prevented 1-methyl-4-phenylpyridinium(MPP+)induced neurotoxicity in SHSY5Y cells,by increasing GSH and GSH/GSSG ratio,and reducing reactive oxygen species.In addition,the neuroprotective effects of TFA were associated with its ability to restore MPTP/MPP+induced downregulation of SLC7A11 and glutathione peroxidase 4(GPX-4).In conclusion,we demonstrated that TFA exerted significant neuroprotection against MPTP/MPP+induced neurodegeneration by inhibiting ferroptosis through the regulation of SLC7A11/GPX-4 axis,suggesting the use of TFA as a possible food supplement in the prevention of PD.
基金Supported by Undergraduate Innovation and Entrepreneurship Training Program of Guizhou University of Traditional Chinese Medicine(GZYDCHZ[2019]42)National Key R&D Plan(2019YFC1712500)Guizhou Provincial Science and Technology Planning Project(QKHHBZ[2020]3003).
文摘[Objectives]This study was conducted to investigate the effects of Astragalus membranaceus in different groups on energy metabolism and CNTF protein expression in skeletal muscle of exercise-induced fatigue rats.[Methods]Thirty-five clean male SD rats were randomly divided into a normal group,and low-,meddle-and high-dose groups of A.membranaceus aqueous solution,with 7 rats in each group.The low-dose,medium-dose and high-dose groups were given by gavage at 0.65,1.3 and 2.6 g/kg,respectively,while the normal group and the model group were given normal food and water.The weight of rats was observed.The contents of serum urea,lactate,muscle glycogen,liver glycogen and CNTF expression were detected.[Results]After modeling,compared with the normal group,the serum lactate and urea contents of rats in the model group significantly increased(P<0.01),while the muscle glycogen content(P<0.01)and liver glycogen content(P<0.05)of the skeletal muscle significantly decreased.Compared with the model group,the low-,meddle-and high-dose groups of A.membranaceus significantly reduced the levels of lactate and urea in serum(P<0.01),while the levels of muscle glycogen and liver glycogen in the skeletal muscle significantly increased(P<0.01,P<0.05).[Conclusions]This study provides a good research foundation for the treatment of exercise-induced fatigue using traditional Chinese herb A.membranaceus in modern clinical practice.
基金supported by the National Natural Science Foundation of China(No.81473538,81873189)the Key R&D Program of Ningxia Hui Autonomous Region,China(2017BY079,2018ZWYQ0077)China Agricultural Research System(CARS-21)
文摘As a traditional Chinese medicine,the root of Astragalus membranaceus var.mongholicus(AMM)or A.membranaceus(AM)has been widely used in China and other Asian countries for thousands of years.Till now,the flavonoids,phenolic acids and saponins are considered as the main active components contributing to their therapeutic effect in these plants.In order to clarify the distribution and contents of these compounds in different organs of these plants,a rapid and sensitive analytical method for simultaneous determination of 25 active compounds including seven types(i.e.dihydroflavones,isoflavane,isoflavones,flavones,pterocarpans,phenolic acid and saponins)within 10 min was established using ultra-pressure liquid chromatography coupled with tandem mass spectrometry(UPLCeMS/MS).Then,the established method was fully validated and successfully applied to the determination of the contents of these analytes in different parts(root,rhizome,stem,leaf and flower)of AMM and AM.The results indicated that the contents of the same type of compounds in two different species plants were significantly different.Moreover,the obvious differences were also found for the distribution and contents of different type of compounds in five organs of the same species.The present study could provide necessary information for the rational development and utilization of AMM and AM resource.
文摘A new isoflavane named astraganoside,together with five known compounds had been isolated from the processed Astragralus membranaceus.The structure of the novel compound was elucidated as(3R,4R)-3-(2-hydroxy-3,4-dimethoxyphenyl)chroman- 4,7-diol-7-O-β-D-glucopyranoside(1)based on spectroscopic methods including UV,IR,ESI-MS,1D NMR and 2D NMR techniques.
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National Natural Science Foundation of China Regional Science Fund Project (81673862, 81660833, 81760814)Guizhou Provincial Department of Education Project (Qian jiao yan he GZS ZI[2016]08)+2 种基金Guizhou Postgraduate Workstation Program (Educational Hall) Project (Qian jiao yan he JYSZ ZI[2014]018)Guizhou Science and Technology Department Project [Qian ke he ren cai(2016)4032]Guizhou Provincial Organization Department Project (Qian ren ban fa[2018] No. 3).
文摘Objective: To explore the anti-cancer mechanism of active ingredients of Astragalus membranaceus (AM) through network pharmacology. Methods: TCMSP, PubChem, STICTH and GeneCards databases were used to predict and screen the main active ingredients and anti-cancer targets of AM. Active ingredient-target-disease network was constructed by Cytoscape 3.7.0 software, and protein interaction network was constructed by STRING platform. KEGG signaling pathway and GO biological process of targets were analyzed by Bioconductor database. Results: Twenty-four active ingredients were screened from AM, which acted on 106 cancer targets such as PTGS, NCOA2, ADRB2, PRSS1, NOS2, NOS3, GABRA1. Through these targets, the anti-cancer effect of AM mainly acts on small cell lung cancer, colorectal cancer, thyroid cancer, breast cancer, non-small cell lung cancer, hepatocellular carcinoma, pancreatic cancer, gastric cancer, endometrial cancer, enriched in chemical carcinogenesis, Platinum drug resistance, Epstein-Barr virus infection, TNF signaling pathway, Toll-like receptor signaling pathway, p53 signaling pathway, VEGF signaling pathway, NF-kappa B signaling pathway, and PI3K - Akt signaling pathway. Conclusion: This study found that the main anti-cancer compounds of AM are kaempferol, quercetin, 7-O-methylisomucronulatol, formononetin, isorhamnetin, Calycosin, 3,9-di-O-methylnissolin. The main targets include PTGS, PTGS1, NCOA2, ADRB2, PRSS1, NOS2, NOS3, GABRA1, F2. The mechanisms involved in anticancer could be summarized as following: blocking the chemical carcinogenesis, reversing the platinum drug resistance, anti - Epstein - Barrvirus infection, and inhibiting cell proliferation related signaling pathways, such as TNF signaling pathway, Tolllike receptor signaling pathway, p53 signaling pathway, VEGF signaling pathway, NF-kappa B signaling pathway, PI3K - AKT signaling pathway.
基金This research was supported by the National Natural Science Foundation of China(Grant No.81603438).
文摘Objective:Prostate cancer(PCa)is the second most common male malignancy tumor in the world,and the occurrence rate and the mortality of PCa keeps increasing nowadays,exploration of accurate biomarker and predict clinical outcome of PCa is of great significance.Traditional Chinese medicine Huangqi(Astragalus membranaceus,AM)has been widely used for PCa treatment in China,while the pharmacological mechanisms are still unclear.The current paper intend to perform a network pharmacology analysis to reveal the mechanism of the effects of AM in PCa.Methods:Traditional Chinese Medicine Systems Pharmacology Database(TCMSP)was used to obtain chemical constituents of AM.PCa-related target genes were collected via OMIM and GeneCards databases.PCa-AM common target protein interaction network was established by the STRING database.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed to further explore the PCa mechanism and therapeutic effect of AM.The network diagrams of the active component-action target and protein-protein interaction(PPI)networks were constructed using Cytoscape software.Results:A total of 20 active ingredients contained and 462 putative identified target genes were screened from AM,of which 46 overlapped with the targets of PCa and were considered potential therapeutic targets.The analysis of the network results showed that the AM activity components quercetin,kaempferol,isorhamnetin,3,9-di-O-methylnissolin and 7-O-methylisomucronulatol have a good binding activity with top ten screened targets,such as MYC,AKT1,CCND1,MAPK1,CASP3,EGFR,ESR1,VEGFA,ERBB2 and IL-6.GO and KEGG analyses revealed that these targets were associated with proteoglycans in cancer,virus infection,microRNAs in cancer,PI3K-Akt signaling pathway,and other biological process.Conclusion:This study demonstrated the multicomponent,multitarget,and multichannel characteristics of AM,which provided a novel approach for further research of the mechanism of AM in the treatment of PCa.
文摘A new isoflavone glucoside, 3’-methoxy-5’-hydroxy-isoflavone-7-O-β-D-glucoside, was isolated from the roots of Astragalus membranaceus and its structure waselucidated by spectroscopic data.
文摘Objective:To evaluate the mechanism of Astragalus membranaceus(AM)by intervening peritoneal mesothelial cells(PMCs),epithelial-mesenchymal transition(EMT),and spleen deficiency syndrome(SDS)in peritoneal fibrosis(PF),we base on employing the strategy of Q-marker theory combination network pharmacology method.Methods:First,we obtained the Q-markers of AM by searching the relevant literature and its pharmacological information was collected based on SwissADME.The SwissTargetPrediction and pharmmaper were employed to predict its potential target.Secondly,GeneCards,DisGeNET,and OMIM databases were employed to search the related targets of EMT,SDS,and PF.VENNY2.1 tool was employed to obtain the intersection targets of AM and the three;then the“AM potential target-SDS-EMT-PF”Venn diagram was constructed.The common targets of AM,EMT and SDS were uploaded to the STRING database and obtained the PPI protein interaction network map.Cytoscape 3.7.2 was employed to evaluate the core target of PPI network.PATHER and Metascape databases were used to analyze protein type,GO biological process,and KEGG pathway.Finally,a network diagram of the“TCM-component-disease target-pathway”was drawn.Results:A total of 10 AM Q-makers were screened out,corresponding to 335 targets of AM,2,728 targets of SDS,373 of EMT,and 612 PF targets were found.Among them,there are 155 common AM targets related to SDS and EMT.Key targets such as ALB,AKT1,VEGFA,TNF,EGFR,CASP3,SRC,STAT3,HSP90AA1,and ESR1 were obtained.The core drug include quercetin,astragalosideIII,Calycosin-7-O-beta-D-glucoside,astragalosideIV,etc.The types of PPI proteins include protein modification enzymes,metabolite transferases,transmembrane signal receptors,etc.Biological processes include the regulation of kinase activity,the positive regulation of transferase activity,and the regulation of kinase activity.The key pathways may include PI3K-Akt signaling pathways,the non-smad pathway of the TGF-βsignaling pathway,and the AGE-RAGE signaling pathway.Conclusion:AM could prevent and treat PF through a multi-component multi-target-multi-path mechanism.Astragalus saponins may be the main component types of AM intervening EMT pathology by strengthening the spleen and nourishing Qi.AstragalosideIV and astragalosideIII may be the constituents that can invigorate the spleen and replenish Qi.The results of this study contribute to a more comprehensive understanding of the critical components and mechanisms of AM by intervening SDS and EMT in the treatment of PF.
基金Supported by Creative Research Group of Affiliated First Hospital of Hunan Traditional Chinese Medical College,China(No.2021B-003)Key Plans of Hunan Administration of Traditional Chinese Medicine,China(No.201915)+2 种基金Natural Science Foundation of Hunan Province,China(No.2018JJ6043)Health and Family Planning Commission of Hunan Province,China(No.B20180815)Technology Plan Project of Zhuzhou City,Hunan Province,China(No.2021-009)。
文摘The primary chemical components of Astragalus membranaceus include polysaccharides,saponins,flavonoids,and amino acids.Recent studies have shown that Astragalus membranaceus has multiple functions,including improving immune function and exerting antioxidative,anti-radiation,anti-tumor,antibacterial,antiviral,and hormone-like effects.Astragalus membranaceus and its extracts are widely used in clinical practice because they have obvious therapeutic effects against various autoimmune diseases and relatively less adverse reaction.Multiple sclerosis(MS)is an autoimmune disease of central nervous system(CNS),which mainly caused by immune disorder that leads to inflammatory demyelination,inflammatory cell infiltration,and axonal degeneration in the CNS.In this review,the authors analyzed the clinical manifestations of MS and experimental autoimmune encephalomyelitis(EAE)and focused on the efficacy of Astragalus membranaceus and its chemical components in the treatment of MS/EAE.
基金supported by the National Key Research and Development Program of China(2020YFA0908000)CAMS Innovation fund for Medical Sciences(CIFMS,No.2021-I2M-1029,China)Beijing Key Laboratory of non-Clinical Drug Metabolism and PK/PD Study(Z141102004414062)。
文摘Astragalosides are the main active constituents of traditional Chinese medicine Huang-Qi,of which cycloastragenol-type glycosides are the most typical and major bioactive compounds.This kind of compounds exhibit various biological functions including cardiovascular protective,neuroprotective,etc.Owing to the limitations of natural sources and the difficulties encountered in chemical synthesis,re-engineering of biosynthetic machinery will offer an alternative and promising approach to producing astragalosides.However,the biosynthetic pathway for astragalosides remains elusive due to their complex structures and numerous reaction types and steps.Herein,guided by transcriptome and phylogenetic analyses,a cycloartenol synthase and four glycosyltransferases catalyzing the committed steps in the biosynthesis of such bioactive astragalosides were functionally characterized from Astragalus membranaceus.AmCAS1,the first reported cycloartenol synthase from Astragalus genus,is capable of catalyzing the formation of cycloartenol;AmUGT15,AmUGT14,AmUGT13,and AmUGT7 are four glycosyltransferases biochemically characterized to catalyze 3-O-xylosylation,3-O-glucosylation,25-O-glucosylation/O-xylosylation and 2’-O-glucosylation of cycloastragenol glycosides,respectively.These findings not only clarified the crucial enzymes for the biosynthesis and the molecular basis for the structural diversity of astragalosides in Astragalus plants,also paved the way for further completely deciphering the biosynthetic pathway and constructing an artificial pathway for their efficient production.
基金the Major Projects of the Natural Science Foundation of Gansu,China(No.18JR4RA001)the Major Special Projects of Gansu,China(No.21ZD2JA002)the Natural Science Foundation of Gansu Province(No.20JR5RA564).
文摘The water-based foam stabilized by the natural surfactant applied in the fabrication of porous materials has attracted extensive attention,as the advantages of cleanness,convenience and low cost.Particularly,the development of a green preparation method has became themain research focus and frontier.In thiswork,a green liquid foamwith high stability was prepared by synergistic stabilization of natural plant astragalus membranaceus(AMS)and attapulgite(APT),and then a novel porous material with sufficient hierarchical pore structure was templated from the foam via a simple free radical polymerization of acrylamide(AM).The characterization results revealed that the amphiphilic molecules from AMS adsorbed onto thewater-air interface and formed a protective shell to prevent the bubble breakup,and APT gathered in the plateau border and formed a three-dimensional network structure,which greatly slowed down the drainage rate.The porous material polyacrylamide/astragalus membranaceus/attapulgite(PAM/AMS/APT)showed the excellent adsorption performance for cationic dyes of Methyl Violet(MV)and Methylene Blue(MB)in water,and the maximum adsorption capacity could reach to 709.13 and 703.30 mg/g,respectively.Furthermore,the polymer material enabled to regenerate and cycle via a convenient calcination process,and the adsorption capacitywas still higher than 200 mg/g after five cycles.In short,this research provided a new idea for the green preparation of porous materials and the treatment of water pollution.
基金supported by the National Natural Science Foundation of China(Nos.30772753,81173254,and 81673940)the Science and Technology Program of Guangzhou(No.20160701335)the First-class discipline construction major project of Guangzhou University of Chinese Medicine(Guangzhou University of Chinese Medicine Planning,2018-No.6)
文摘Astragalus membranaceus(Radix Astragali, RA) and Atractylodes macrocephala(Rhizoma Atractylodis Macrocephalae, RAM) are often used to treat gastrointestinal diseases. In the present study, we determined the effects of polysaccharides extracts from these two herbs on IEC-6 cell migration and explored the potential underlying mechanisms. A migration model with IEC-6 cells was induced using a single-edged razor blade along the diameter of cell layers in six-well polystyrene plates. The cells were grown in control--media or media containing spermidine(5 μmol·L^(-1), SPD), alpha-difluoromethylornithine(2.5 mmol·L^(-1), DFMO), 4-Aminopyridine-(40 μ-mol·L^(-1), 4-AP), the polysaccharide extracts of RA or RAM(50, 100, or 200 mg·L^(-1)), DFMO plus SPD, or DFMO plus polysaccharide extracts of RA or RAM for 12 or 24 h. Next, cytosolic free Ca^(2+)([Ca^(2+)]cyt) was measured using laser confocal microscopy, and cellular polyamine content was quantified with HPLC. Kv1.1 mRNA expression was assessed using RT-qPCR and Kv1.1 and RhoA protein expressions were measured with Western blotting analysis. A cell migration assay was carried out using Image-Pro Plus software. In addition, GC-MS was introduced to analyze the monosaccharide composition of both polysaccharide extracts. The resutls showed that treatment with polysaccharide extracts of RA or RAM significantly increased cellular polyamine content, elevated [Ca^(2+)]cyt and accelerated migration of IEC-6 cells, compared with the controls(P < 0.01). Polysaccharide extracts not only reversed the inhibitory effects of DFMO on cellular polyamine content and [Ca^(2+)]cyt, but also restored IEC-6 cell migration to control level(P < 0.01 or < 0.05). Kv1.1 mRNA and protein expressions were increased(P < 0.05) after polysaccharide extract treatment in polyamine-deficient IEC-6 cells and RhoA protein expression was increased. Molar ratios of D-ribose, D-arabinose, L-rhamnose, D-mannose, D-glucose, and D-galactose was 1.0:14.1:0.3:19.9:181.3:6.3 in RA and 1.0:4.3:0.1:5.7:2.8:2.2 in RAM. In conclusion, treatment with RA and RAM polysaccharide extracts stimulated migration of intestinal epithelial cells via a polyamine-Kv1.1 channel activated signaling pathway, which facilitated intestinal injury healing.
文摘Astragalus membranaceus may be a potential therapy for childhood asthma but its driving mechanism remains elusive. The main components of A. membranaceus were identified by HPLC. The children with asthma remission were divided into two combination group(control group, the combination of budesonide and terbutaline) and A. membranaceus group(treatment group, the combination of budesonide, terbutaline and A. membranaceus). The therapeutic results were compared between two groups after 3-month therapy.Porcine peripheral blood mononuclear cells(PBMCs) were isolated from venous blood by using density gradient centrifugation on percoll. The levels of Fox P3, EGF-β, IL-17 and IL-23 from PBMCs and serum Ig E were measured. The relative percentage of Treg/Th17 cells was determined using flow cytometry. The main components of A. membranaceus were calycosin-7-O-glucoside, isoquercitrin, ononin, calycosin, quercetin, genistein, kaempferol, isorhamnetin and formononetin, all of which may contribute to asthma therapy. Lung function was significantly improved in the treatment group when compared with a control group(P < 0.05). The efficacy in preventing the occurrence of childhood asthma was higher in the treatment group than the control group(P < 0.05).The levels of Ig E, IL-17 and IL-23 were reduced significantly in the treatment group when compared with the control group, while the levels of FoxP3 and TGF-β were increased in the treatment group when compared with the control group(P < 0.05). A. membranaceus increased the percentage of Treg cells and reduced the percentage of Th17 cells. A. membranaceus is potential natural product for improving the therapeutic efficacy of combination therapy of budesonide and terbutaline for the children with asthma remission by modulating the balance of Treg/Th17 cells.
基金Supported by the National Natural Science Foundation of China(No.81774282)Beijing Natural Science Foundation(No.7172187)。
文摘The interaction between immune cells and hepatic stellate cells(HSCs)can modulate the development of hepatic fibrosis.It can also regulate hepatic fibrosis and liver cirrhosis caused by excessive deposition of extracellular matrix(ECM).This article reviews the action mechanism of immune cells on liver fibrosis and the effect of Astragalus membranaeus and its active components on immune cells.In-depth study of interaction between immune cells and HSCs on the pathogenesis of liver fibrosis,and the regulatory effect of Astragalus membranaeus and its active components on immune mechanism will provide new insights in the treatment of liver fibrosis.
基金financially supported by the Doctoral Research Fund of Neijiang Normal University(14B07)Scientific Research Fund of Sichuan Provincial Education Department (16ZB0302)
文摘Erythrocytes play an essential role in transporting O_2 and CO_2 for respiration in fish. However,erythrocytes continuously suffer from reactive oxygen species(ROS)-induced oxidative stress and apoptosis. Thus, it is essential to expand our knowledge of how to protect erythrocytes against ROS-induced oxidative stress and apoptosis in fish. In this study, we explored the cytotoxicity and the effects of butylated hydroxyanisole(BHA), ethyl ether extracts, ethyl acetate extracts, acetone extracts(AE), ethanol extracts, and aqueous extracts of Astragalus membranaceus(EAm) on hydroxyl radical(·OH)-induced apoptosis in carp erythrocytes. The rat hepatocytes and carp erythrocytes were incubated with different concentrations of BHA or EAm(0.125 to 1 mg/mL). The toxicity in rat hepatocytes and carp erythrocytes was then measured using a 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide(MTT) assay and a haemolysis assay,respectively. The carp erythrocytes were treated with BHA or EAm in the presence of 40 μmol/L FeSO4 and20 μmol/L H_2 O_2 at 37℃, except for the control group. Oxidative stress and apoptosis parameters in the carp erythrocytes were then evaluated using the commercial kit. The results indicated that at high concentrations, BHA and EAm could induce toxicity in rat hepatocytes and fish erythrocytes. However, BHA was more toxic than EAm at the same concentrations. Moreover, the toxicity order of BHA and EAm in the fish erythrocytes approximately agreed with that for the rat hepatocytes. Butylated hydroxyanisole and EAm suppressed the ·OH-induced phosphatidylserine exposure and DNA fragmentation(the biomarkers of apoptosis) by decreasing the generation of ROS, inhibiting the oxidation of cellular components, and restoring the activities of antioxidants in carp erythrocytes. Of all of the examined EAm, the AE showed the strongest effects. The effects of AE on superoxide anion, H_2 O_2, met-haemoglobin and reduced glutathione levels, as well as glutathione reductase activity and apoptosis were equivalent to or stronger than those of BHA. These results revealed that the AE of Astragalus membranaceus could be used as a potential natural antioxidant or apoptosis inhibitor in fish erythrocytes.
基金supported by the 2019 Yeungnam University Research Grant。
文摘Astragalus membranaceus(A.membranaceus)is a widely used traditional herb in China and Korea.A.membranaceus polysaccharides(AMP),which make up a major part of the root extract,have been shown to modulate immune modulations,especially activation of bone marrow-derived dendritic cells(BMDCs)and T cells.However,the immune stimulatory effect of AMP in the mouse in vivo and human peripheral blood DCs(PBDCs)has not been well investigated.In this study,we found that intravenous(i.v.)injection of AMP in C57 BL/6 mice induced remarkable elevations in co-stimulatory and MHC class I and II molecule levels in the splenic DCs and its subsets.The stimulatory effect of DCs by AMP was elevated 6 h after treatment,which rapidly decreased 18 h after injection.Furthermore,AMP promoted intracellular production of pro-inflammatory cytokines in spleen DC subsets,which contributed elevation of serum cytokine levels.Finally,the AMP promoted PBDC activation.Thus,these results demonstrate that AMP can be used as an immune stimulatory molecules in human and mouse.