Total flavonoids of Astragalus membranaceus protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity in mice by inhibiting ferroptosis through SLC7A11/GPX-4 signaling pathway

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.

Effects of Astragalus membranaceus on Energy Metabolism and Expression of CNTF Protein in Skeletal Muscle of Exercise-induced Fatigue Rats

[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.

Comparative analysis of twenty-five compounds in different parts of Astragalus membranaceus var.mongholicus and Astragalus membranaceus by UPLC-MS/MS

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.

Two new saponins from the aerial part of Astragalus membranaceus var. mongholicus

Two new saponins named mongholicoside A （1） and mongholicoside B （2） were isolated from the aerial part of Astragalus membranaceus var mongholicus. Their structures were determined by 1D and 2D NMR, ESI-MS techniques and chemical methods.

Protective effects of combined Astragalus membranaceus and magnesium ions on global brain ischemia

The traditional Chinese herb Astragalus membranaceus is a well-known treatment for neurological diseases and is considered to exhibit anti-dementia properties.This study investigated the synergistic effects of magnesium ions and Astragalus membranaceus on global brain ischemia in rats.4＇-6-diamidino-2-phenylindole staining demonstrated that the number of living neurons was significantly greater in the rat hippocampus after administration of a combination of Astragalus membranaceus and magnesium,compared with a vehicle group,an Astragalus membranaceus alone group,and a magnesium alone group.Western blot assay revealed that cleaved Caspase-3 protein expression was significantly reduced in the rat hippocampus in the combined Astragalus membranaceus and magnesium group compared with the Astragalus membranaceus alone group and the magnesium alone group.The results suggested that the combination of Astragalus membranaceus and magnesium exhibits a stronger neuroprotective effect on global brain ischemia in rats compared with Astragalus membranaceus or magnesium alone.This effect was associated with decreased Caspase-3 expression.

Chemistry Behind the Immunomodulatory Activity of Astragalus membranaceus

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.

A new isoflavane from processed Astragalus membranaceus

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.

Isolation and Identification of Root Rot Fungus of Astragalus membranaceus

The perennial root of Astragalus membranaceus is used as a medicine, while root rot is a main factor causing reduction of quality and commodity value of A. membranaceus . The screening and research of the pathogenic species and their characteristics could provide theoretical and practical basis for the control of this disease. A pathogenic strain was isolated and purified from the root part of four-year-old A. membranaceus , and identified by morphological and molecular biological methods as Fusarium oxysporum . This study will provide a theoretical basis for the research of the biological characteristics and control of F. oxysporum .

The Effects of Astragalus Membranaceus Extract on Sperm Quality in vitro

This study is to explore the effects on sperm quality and fertilizing ability by using astragalus membranaceus extract as additive among infertile males. Human sperms were cultured in the concentrated astragalus membranaceus extract for 1 h, then semen parameters were measured by the equipment of computer assisted semen analyzer (CASA). The results are as follows: compared with the original semen, the sperm motility and velocity, the percentage of grade A sperms and the swaying frequency of sperm heads were improved markedly in the semen treated with astragalus membranaceus extract (P<0.05). Meanwhile, the astragalus membranaceus aqueous extract was analyzed by atomic absorption spectrophotometer. It was found there exist several metal elements and a certain amount of trace elements in the extract (10 mg/ml). The concentration of K +, Ca 2+ , Zn 2+ were 25.1 μg/ml, 7.28 μg/ml, and 0.47 μg/ml respectively. The influence of this additive on artificial insemination was also discussed. We considered that the studied Chinese herbal medicine additive has good effects on sperm preparation in vitro, and this might be a potential method in assisted reproductive technology.

Bioinformatics analysis of Astragalus membranaceus on the treatment of prostate cancer

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.

A New Isoflavone Glucoside from Astragalus membranaceus

A new isoflavone glucoside, 3'-methoxy-5'-hydroxy-isoflavone-7-O-beta-D-glucoside, was isolated from the roots of Astragalus membranaceus and its structure was elucidated by spectroscopic data.

The mechanism of Astragalus membranaceus in treating peritoneal fibrosis by intervening the key syndrome and pathology based on Q-marker theory

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.

Progress in Mechanism of Astragalus membranaceus and Its Chemical Constituents on Multiple Sclerosis

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.

Fabrication porous adsorbents templated from aqueous foams using astragalus membranaceus and attapulgite as stabilizer for efficient removal of cationic dyes

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.

Functional characterization of a cycloartenol synthase and four glycosyltransferases in the biosynthesis of cycloastragenol-type astragalosides from Astragalus membranaceus

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.

Effect of Astragalus membranaceus injection on the activity of the intestinal mucosal mast cells after hemorrhagic shock-reperfusion in rats

Background The mechanism of mucosal damage induced by ischemia-reperfusion （IR） after hemorrhagic shock is complex; mast cells （MC） degranulation is associated with the mucosal damage. Astragalus membranaceus can protect intestinal mucosa against intestinal oxidative damage after hemorrhagic shock, and some antioxidant agents could prevent MC against degranulation. This study aimed to observe the effects of astragalus membranaceus injection on the activity of intestinal mucosal mast cells （IMMC） after hemorrhage shock-reperfusion in rats Methods Thirty-two Wistar rats were randomly divided into the normal group, model group, low dosage group, （treated with Astragalus membranacaus injection, 10 g crude medication/kg） and high dosage group （treated with Astragalus membranacaus injection, 20 g crude medication/kg）. The rat model of hemorrhagic shock-reperfusion was induced by hemorrhage for 60 minutes followed by 90 minutes of reperfusion. The animals were administrated with 3 ml of the test drug solution before reperfusion. At the end of study, intestinal pathology, ultrastructure of IMMC, and expression of tryptase were assayed. The levels of malondisldehyde （MDA）, TNF-α, histamine, and superoxide dismutase （SOD） activity in intestine were detected, and the number of IMMC was counted. Results The Chiu＇s score of the rats in the model group was higher than in other groups （P〈0.01）. The Chiu＇s score in the high dosage group was higher than that in the low dosage group （P〈0.05）. Hemorrhage-reperfusion induced IMMC degranulation： Astragalus membranaceus injection attenuated this degranulation. Expression of tryptase and the number of IMMC in the model group increased compared with the other groups （P〈0.01） and was significantly reduced by the treatments of Astragalus membranaceus injection at both doses. There was no significant difference between the two treatment groups （P〉0.05）. MDA content and concentration of TNF-α in the model group were higher than that in the other three groups （P〈0.05）, and the concentration of TNF-α in the low dosage group was higher than that in the high dosage group （P〈0.05）. SOD activity and the concentration of histamine in the model group were lower than the other three groups （P〈0.05）. There was a negative correlation between the Chiu＇s score and the concentration of histamine and a positive correlation between the Chiu＇s score and the concentration of TNF-α and between the SOD activity and the concentration of histamine in the four groups （P〈0.05）. Conclusion Astragalus membranaceus injection may reduce the damage to small intestine mucosa by inhibiting the activated IMMC after hemorrhagic shock.

Astragalus Membranaceus Injection Combined with Conventional Treatment for Viral Myocarditis:A Systematic Review of Randomized Controlled Trials

Objective：To assess the efficacy and safety of Astragalus membranaceus Injection combined with conventional therapy in the treatment of viral myocarditis.Methods：Randomized controlled trials（RCTs） of A.membranaceus Injection combined with conventional treatment compared with conventional treatment alone were included.Study population characteristics and outcome results were extracted independently by two assessors.Meta-analysis was performed for data available.Results：Six RCTs,involving 639 participants,were included in this study.The methodological quality of the included trials was generally low,and there was high risk of publication bias in the included trials.The total effective rate of A.membranaceus Injection combined with conventional treatment was significantly higher than that of conventional treatment alone.Compared with conventional treatment,the cointervention treatment group showed significant recovery in myocardium enzyme levels and electrocardiography.Two RCTs reported there were no adverse effects from A.membranaceus Injection combined with conventional treatment.Conclusion：A.membranaceus Injection combined with conventional treatment appeared to be more efficacious compared with conventional treatment alone for treating viral myocarditis.However,this conclusion should be cautiously interpreted due to low methodological quality,small sample size,limited number of trials,and high risk of publication bias and other unidentified risks of bias.The safety of A.membranaceus Injection combined with conventional treatment remains uncertain.

Research Progress in Astragalus Membranaceus and Its Active Components on Immune Responses in Liver Fibrosis

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.

Astragalus membranaceus reduces free radical mediated injury to renal tubules in rabbits receiving high energy shock waves

Background Recent studies have revealed the important role of free radicals in renal damage induced by high energy shock waves (HESW) This study aimed at investigating the effects of Astragalus membranaceus , a traditional Chinese medicinal herb, on free radical mediated HESW induced damage to renal tubules in a live rabbit model Methods Forty five healthy male New Zealand white rabbits were randomly divided into three groups: control group ( n =15), sham group ( n =15), and herb treated group ( n =15) Three days prior to HESW application, the controls received verapamil (0 4 mg/kg), the shams received physiological saline (20 ml), and the herb treated animals received Astragalus membranaceus (2 4 g/kg) intravenously HESW (1500 shocks, 18kV) was applied to the right kidneys of all anesthetized rabbits We measured superoxide dismutase (SOD) and malondialdehyde (MDA) levels before and after shock treatment in blood and kidney homogenates Histopathological changes were also observed Results MDA levels increased and SOD activity decreased significantly in the sham group ( P <0 05 for both) after shock treatment MDA levels showed a much less increase in the controls ( P <0 05) and did not increase to statistically significant levels in the group receiving Astragalus membranaceus ( P >0 05) SOD values were significantly higher in the controls than in the shams ( P <0 05) By contrast, SOD levels recovered rapidly in the rabbits receiving Astragalus membranaceus , reaching a nadir within 24 hours, and returning to baseline more quickly than in control and sham rabbits ( P <0 05) Histopathological examinations showed that renal tubular damage in the controls was less severe than in the shams, while damage in the Astragalus membranaceus group was even more mild, with rapid recovery in comparison with the controls Conclusion This study provides preliminary evidence indicating that Astragalus membranaceus has strong protective effects on free radical mediated renal tubular damage induced by HESW and that these effects are superior to the effects of verapamil

Mechanisms of the therapeutic effect of astragalus membranaceus on sodium and water retention in experimental heart failure

OBJECTIVE: To investigate the therapeutic effect of Astragali on sodium and water retention in aortocaval fistula-caused experimental congestive heart failure and its involved mechanisms. METHODS: In aortocaval fistula-caused chronic (5 wk), heart failure rats treated with and without Astragali 1.0 g/day intraperitoneally, changes of cardiac and renal function, renal response to atrial natriuretic peptide (ANP) were examined. Dot blot analysis was used to determine the effect of Astragali on hypothalamic arginine vasopresin (AVP) mRNA expression, and mRNA expressions of aortic and renal AVP V1a receptor, renal AVP V2 receptor and aquaporin-2 (AQP2) were simultaneously detected by RT-PCR method. RESULTS: Rats with aortocaval fistula impaired cardiac and renal functions evidenced by higher right atrial pressure (RAP), left ventricular end-diastolic pressure (LVEDP), lower + dP/dtmax of left ventricle, glomerular filtration rate (GFR), renal plasma flow (RPF), urine volume (UV), urinary sodium excretion (UNaV) and free water clearance (CH2O) compared with sham-operated control (P