Study on the effect of addition or subtraction of Astragalus membranaceus and Draba nemorosa on CHF and changes of cardiac color ultrasound parameters / 中国现代医生

@#Objective To analyze the efficacy of Astragalus membranaceus and Draba nemorosa in the treatment of chronic heart failure(CHF),the change of cardiac color ultrasound parameters and its predictive value for adverse end events.Methods A total of 92 patients with Qi-deficiency and blood-stasis combined with Shuiyin CHF treated in Wenzhou Hospital of Traditional Chinese Medicine from September 2019 to September 2021 were randomly selected and divided into two groups by random number table method,with 46 cases in each group.Patients in control group were received conventional Western medicine treatment,and patients in observation group were received the addition and subtraction treatment of Yiqi Huoxue Lishui prescription based on Astragalus membranaceus and Draba nemorosa.The clinical efficacy,TCM syndrome score,heart color ultrasound parameters and the incidence of adverse endpoint events within 6 months were compared between the two groups.Cardiac color doppler ultrasound parameters were compared between the occurrence group and the non-occurrence group,and receiver operating characteristic curve was drawn to analyze the predictive value of cardiac color Doppler ultrasound parameters for adverse end events.Results The total clinical effective rate of the observation group(95.65%)was higher than that of the control group(71.74%)(P<0.05).After treatment,palpitation,weakness,shortness of breath,lethargy and lip purple score in observation group were lower than those in control group(P<0.05).The left ventricular end-diastolic diameter(LVEDD)and left arial diameters(LAD)of the observation group were lower than those of the control group after treatment(P<0.05).After treatment,the left ventricular ejection fraction(LVEF)of the observation group was higher than that of the control group(P<0.05);The incidence of adverse endpoint events within 6 months in the observation group(2.17%)was lower than that in the control group(19.57%)(P<0.05).The LVEDD and LAD in the adverse end point event group were higher than those in the without adverse end point event group(P<0.05),and the LVEF was lower than that in the without adverse end point event group(P<0.05).The area under the curve(AUC)of LVEDD,LAD and LVEF combined to predict the occurrence of adverse endpoint events was 0.812,and the 95%CI confidence interval was 0.734-0.968;The sensitivity of combined detection(93.42%)was higher than that of single detection(71.52%,75.11%,79.62%)(P<0.05).The specificity of combined detection(82.27%)compared with that of single detection(70.19%,73.07%,77.28%)(P>0.05).Conclusion Supplementing qi and promoting blood circulation and rehydrating water based on Astragalus membranaceus and Draba nemorosa can effectively improve the cardiac function of CHF patients,alleviate symptoms such as palpitations and fatigue,and reduce the incidence of adverse endpoint events.In addition,the combined detection of cardiac ultrasound parameters can improve the prediction efficiency of adverse endpoint events,which has certain clinical value.

Astragalus polysaccharide inhibits liver injury in mice with viral hepatitis by reducing immune inflammation / 中国免疫学杂志

Objective:To observe the effect of astragalus polysaccharides on liver injury in mice with viral hepatitis,and to investigate whether it can regulate the expression of nucleotide-binding oligomerization domain 1(NOD1)/receptor-interacting protein 2(RIP2)/nuclear factor-κB(NF-κB)immune inflammation mediated by signaling pathway plays a protective role in liver.Methods:Sixty female C3H/HeJ mice were divided into modeling group(50 mice)and normal group(10 mice)using a random number table.The mouse model of viral hepatitis was established by intraperitoneal injection of mouse hepatitis virus type 3(MHV-3)in the modeling group.After the successful modeling was confirmed,the surviving mice were divided into thymus peptide group(10 μg),astragalus polysaccharide low,medium and high dose groups(100,200,400 mg/kg astragalus polysaccharide lyophilized in 1 ml/100 g body weight saline)and model group by random number table.Model group and normal group were given the same amount of normal saline intraperitoneal injection,each group was given once a day for 1 month.Results:The model was confirmed by HE staining of liver tis-sue and detection of viral plaque.Compared with the normal group,the liver index,serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL)and tumor necrosis factor-α(TNF-α),IL-1β and IL-8,viral plaques in liver tissue,NOD1,RIP2 and NF-κB p65 expressions and p-NF-κB p65 level in the model group increased(P<0.05),and the liver tissue showed severe pathological changes.Compared with the model group,the liver indexes,serum ALT,AST,TBIL and TNF-α,IL-1β and IL-8,viral plaques in liver tissue,NOD1,RIP2 and NF-κB p65 expressions and p-NF-κB p65 level in the thymosin group and astragalus polysaccharide each 3-dose groups decreased(P<0.05),and the pathological changes of liver tissue were alleviated.The effect of astragalus polysaccharide was dose-dependent,and there were no significant differences in these indexes between thymosin group and astragalus polysaccharide medium dose group(P>0.05).Conclusion:Astragalus polysaccharides can improve the liver function of mice with viral hepatitis,reduce the inflammatory response and pathological changes of liver tissue,reduce the level of virus,specu-late and inhibit NOD1/RIP2/NF-κB pathway and down-regulate NOD1,RIP2 and NF-κB p65 expressions,inhibit p-NF-κB p65 level,and high dose of astragalus polysaccharide has the best effect,which is better than thymosin-α1.

Prediction of the Potential Habitat of Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao in Gansu Province Based on the Maximum Entropy Model and Analysis on Its Ecological Characteristics / 中国中医药信息杂志

Objective To investigate the effects of climate change on the geographical distribution of Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao in Gansu Province,and predict its potential habitat;To provide a theoretical basis for resource conservation of cultivation of A.membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao.Methods Based on the distribution data of A.membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao from field surveys,the maximum entropy model and geographic information system were used to simulate its potential habitat in Gansu Province for the current(1970-2000)and future(2041-2060)periods,and the contribution of environmental factors and the results of the knife-cut test were integrated to assess the important factors governing the distribution of A.membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao.Results The dominant environmental variables governing the geographical distribution of A.membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao were precipitation in the wettest month,average temperature in the wettest season,and elevation.The potential suitable area of A.membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao in Gansu Province under current climatic conditions was 65 902.66 km2,and the high suitable area was mainly concentrated in Dingxi District.In the future period,the suitable areas of A.membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao under the scenarios of SSP126,SSP370 and SSP585 all showed a decreasing trend,especially the area of the high suitable areas decreased significantly.Conclusion Future climate change will lead to a significant reduction in the suitable habitat for A.membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao in Gansu Province.The suitable habitat will mainly move towards high-altitude mountainous areas,and the continuity of A.membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao resources can be maintained by establishing ecological protection zones.

Study on the compositional changes in Astragali Radix before and after honey-frying based on UPLC-Q-TOF/MS and molecular network / 国际中医中药杂志

Objective:To analyse the composition of Astragali Radix and its honey-processed products through a combination of UPLC-Q-TOF/MS and molecular network; To compare the changes in the main components of Astragali Radix before and after honey-frying.Methods:The aqueous extracts of Astragali Radix before and after honey-frying were prepared, and the compositions were detected by UPLC-Q-TOF/MS, analyzed and identified by the Global Natural Products Molecular Network Analysis Platform (GNPS). The generated molecular networks were visualized and analyzed using Cytoscape 3.9.1 software. The compounds were identified by Masslynx 4.2 software based on the secondary fragmentation information of the compounds, and the changes in the content of the components before and after the processing of Astragali Radix were analysed.Results:47 flavonoids and 34 triterpenoid saponins were presumably identified from Astragali Radix and its honey-frying products using the above analytical methods, with about 87% of the flavonoids and about 82% of the saponins decreasing in content after honey-frying.Conclusions:The compositional changes of Astragali Radix before and after honey-frying are rapidly resolved and visualised by liquid-quantity coupling combined with molecular network. It is found that some of the flavonoids and saponins components of Astragali Radix underwent hydrolysis after honey-frying and it may be the material change basis for processing efficiency enhancement.

Effect and mechanism of Astragalus polysaccharide on peritoneal fibrosis and angiogenesis in peritoneal dialysis rats / 中国药房

OBJECTIVE To investigate the effect and mechanism of Astragalus polysaccharide （APS） on peritoneal fibrosis and angiogenesis in rats with peritoneal dialysis （PD）. METHODS Rats were randomly divided into normal control group （Control group）， model group （PD group）， 70 mg/kg APS group （APS-L group）， 140 mg/kg APS group （APS-H group）， and 140 mg/kg APS+40 mg/kg hypoxia-inducible factor-1α （HIF-1α） agonist DMOG group （APS-H+DMOG group）， with 12 rats in each group. PD rat models were constructed in the last four groups of rats. Administration groups were given APS intragastrically and DMOG intraperitoneally. Control group and PD group were given constant volume of normal saline intragastrically， once a day， for 4 consecutive weeks. After the last medication， the peritoneal ultrafiltration （UF）， mass transfer of glucose （MTG）， the levels of serum creatinine （Scr） and blood urea nitrogen （BUN） were detected in rats； peritoneal histomorphology and peritoneal fibrosis （peritoneal thickness and proportion of collagen fiber deposition） were observed； the microvascular density and the expression levels of α-smooth muscle actin （α-SMA）， laminin （LN）， HIF-1α and vascular endothelial growth factor （VEGF） proteins were detected in peritoneal tissue of rats. RESULTS Compared with Control group， the mesothelium of rats in the PD group was loosely arranged and shed， inflammatory cells infiltrated， the peritoneal thickness and proportion of collagen fiber deposition were increased significantly （P＜0.05）. The levels of MTG， Scr and BUN in serum， microvascular density and the expressions of α-SMA， LN， HIF-1α and VEGF proteins were significantly increased， while the level of UF was significantly decreased （P＜ 0.05）； compared with PD group， the levels of above indexes were significantly reversed in APS-L and APS-H groups （P＜0.05）， and the improvement of APS-H group was better than APS-L group （P＜0.05）. Compared with APS-H group， the levels of above indexes in APS-H+DMOG group were all reversed （P＜0.05）. CONCLUSIONS APS inhibits peritoneal fibrosis and angioge-nesis in PD rats by inhibiting HIF-1α/VEGF signaling pathway.

Study on the mechanism of astragalus glycyrrhiza decoction regulating SIRT1 / FOXO1 pathway to prevent QT interval prolongation induced by arsenic trioxide based on metabolomics / 中国临床药理学与治疗学

AIM: To explore the protective effect of astragalus glycyrrhiza decoction (AGD) on arsenic trioxide (ATO)-induced QT interval prolongation and its mechanism based on metabonomics. METHODS: The model of ATO-induced QT interval prolongation in rats was established, and ECG, blood routine, and metabonomics were detected, and the key targets were collected combined with network pharmacology. The possible candidate genes and pathways for the protective effect of AGD were screened by GO and KEGG enrichment analysis and then verified by experiments in vitro. RESULTS: AGD could significantly alleviate the ATO-induced QT interval of SD rats. GO enrichment analysis was mainly related to inflammatory response, reactive oxygen species, oxidative stress, inner cell vesicles, folds, inner cell vesicles, SMAD binding, R-SMAD binding, and signal receptor activator activity. KEGG analysis showed that it was mainly concentrated in the PI3K-Akt signal pathway, lipid and arteriosclerosis, FOXO signal pathway, TNF signal pathway, HIF-1, and other signal pathways. Through the H9c2 cell model in vitro, it was verified that AGD could reverse the expression of SIRT1 and FOXO1 proteins. CONCLUSION: AGD may improve the ATO-induced QT interval prolongation and reduce the cardiotoxicity of ATO by regulating the SIRT1 / FOXO1 signal pathway.

Mechanism of Active Ingredients of Astragalus Membranacus in Treating Heart Failure： A Review / 中国实验方剂学杂志

Heart failure is one of the main cardiovascular system diseases at present， and it is a clinical syndrome caused by changes in cardiac structure and function， resulting in impaired ejection function or ventricular filling. Therefore， heart failure has become the most important cardiovascular disease in the 21st century. In recent years， the incidence of heart failure is increasing， and the survival rate of patients with heart failure is very low. Traditional Chinese medicine has rich experience in preventing and treating heart failure. With the modernization of traditional Chinese medicine， more and more attention has been paid to the research， development， and application of active ingredients in traditional Chinese medicine. Traditional Chinese medicine has unique advantages in improving the heart function of patients with heart failure by treating multiple targets and multiple pathways through syndrome differentiation. Astragalus membranacus， a traditional Chinese medicine， is a kind of medicine that benefits Qi and blood circulation and removes evil spirits. It has the functions of improving myocardial energy metabolism and hemodynamics， protecting myocardial muscle， and promoting angiogenesis. Astragalus membranaceus is often used to treat patients with heart failure， yielding remarkable results. In recent years， it has been found that astragaloside， Astragalus polysaccharide， quercetin， calyx isoflavones， and other main active ingredients of Astragalus membranacus can improve cardiac function and treat heart failure by inhibiting inflammatory response， myocardial apoptosis， and myocardial fibrosis. This paper reviewed the research progress of the action and mechanism of the active ingredients of Astragalus membranacus in the treatment of heart failure by studying relevant literature， with a view to providing a reference for its further research， development， and application in the prevention and treatment of heart failure.

Specific PCR for Identification of Astragalus membranaceus var. mongholicus Seeds， A. membranaceus Seeds， and Adulterants / 中国实验方剂学杂志

ObjectiveTo establish a method based on specific polymerase chain reaction （PCR） that can accurately and rapidly identify Astragalus membranaceus var. mongholicus （AMM） seeds and A. membranaceus （AM） seeds. MethodThe Chloroplast Genome Information Resource （CGIR） and IdenDSS were used to obtain the characteristic DNA fragments of AMM and AM， and the specific single nucleotide polymorphism （SNP） sites of AMM and AM were screened out， on the basis of which the specific primers MG-F/MG-R of AMM and MJ-F/MJ-R of AM were designed. The specific PCR method for identifying AMM and AM was established and optimized， and the specificity and applicability of the method were investigated. ResultThe specific PCR conditions for the identification of AMM were primers MG-F/MG-R， annealing at 62 ℃， and 28 cycles. After PCR amplification and gel electrophoresis， the specific band appeared at about 220 bp， with no band for the seeds of AM or adulterants. The specific PCR conditions for identifying the AM were primers MJ-F/MJ-R， annealing at 58 ℃， and 28 cycles. After PCR amplification and gel electrophoresis， the band appeared at about 150 bp， with no band of AMM or adulterants. ConclusionThe specific PCR method established in this study can accurately and quickly identify the seeds of AMM and AM， which provides a basis for the classification and accurate identification of Astragalus seeds and adulterants.

Targeted metabolomic analysis of phenylpropanoid metabolites in Astragalus membranaceus var. mongholicus in response to Fusarium solani infection / 药学学报

Root rot severely restricts the sustainable development of Astragalus membranaceus var. mongholicus (AMM) industry. Resistance breeding is an economical and environmentally safe way to manage the disease and its key lies in the obtaining of resistance indicators. This study aimed to quickly and accurately screen the resistance-related (RR) metabolites so as to provide reference for the screening of indicators of AMM breeding for resistance. LC-MS-based targeted metabolomics and real-time quantitative PCR technology were employed, in combination with multivariate statistical analysis, in analyzing the dynamic changes of phenylpropanoid metabolites in AMM in response to root rot pathogen Fusarium solani (FS) infection and identifying the differential metabolites. The LC-MS method established showed high sensitivity; each metabolite had a good linear relationship (R2 ≥ 0.968 9) in the corresponding linear range of the respective standard curve; the recoveries and the relative standard deviations (RSDs) (n = 6) ranged from 70% to 107% and from 1.2% to 9.9%, respectively. Obvious disturbances were observed in the changes of the targeted metabolites in AMM infected by FS. These metabolites, compared with the mock-inoculated (CK) group, showed different up or down regulation with time series. Calycosin-7-O-β-D-glucoside, ononin, calycosin and formononetin were identified as differential metabolites, and they all belong to flavonoids. The first three compounds were significantly negatively correlated (r ≤ -0.97, P < 0.05) with the content of FS in the root of AMM. As potential RR metabolites, they are helpful in obtaining promising resistance indicators for AMM against FS infection.

Analysis of Fusarium oxysporum infection on changes of Astragalus metabolism by metabolomic approach / 药学学报

italic>Astragalus is a commonly used Chinese medicinal material in traditional Chinese medicine (TCM), and with the increase of planting area in recent years, the damage of Astragalus root rot has worsened year by year, which seriously affecting its quality and yield. Fusarium oxysporum is one of the main pathogens causing root rot in astragalus. In this study, UPLC-Q-TOF-MS based metabolomic approach combined with multivariate statistical analysis were used to analyze the metabolite changes of Astragalus in response to F. oxysporum infection. The results showed that 62 metabolites in the Astragalus had significant changes after inoculation of F. oxysporum. Polar metabolites included 40 flavonoids, 8 saponins, 2 nucleosides, 1 vitamin, 1 organic acid, 1 amino acid; while lipid metabolites included 3 fatty acids, 1 diradylglycerols, 2 lysophosphatidylcholine, 1 lysophosphatidylglycerol, 1 phosphatidylinositol, 1 sterol lipid. Among these differential metabolites, the relative content of flavonoids, vitamin B2, tryptophan and salicylic acid were increased, while the relative content of saponins were decreased. Correlation analysis showed that the flavonoids were positively correlated with each other, and positively correlated with most lipids, but negatively correlated with most saponins. In addition, studies have shown that F. oxysporum infection is not an influencing factor for the generation of malonyl substitution of flavonoid. This study elucidates the effect of F. oxysporum infection on Astragalus from the perspective of plant metabolism, which provides a basis for exploring the interaction mechanism between the Astragalus and F. oxysporum and further promoting molecular breeding.

Anti-obesity and Gut Microbiota Modulation Effect of Astragalus Polysaccharides Combined with Berberine on High-Fat Diet-Fed Obese Mice / 中国结合医学杂志

OBJECTIVE@#To investigate whether astragalus polysaccharides (APS) combined with berberine (BBR) can reduce high-fat diet (HFD)-induced obesity in mice.@*METHODS@#Except for normal mice, 32 HFD-induced obese mice were randomized into HFD, APS (1,000 mg/kg APS), BBR (200 mg/kg BBR), and APS plus BBR (1,000 mg/kg APS plus 200 mg/kg BBR) groups, respectively. After 6-week treatment (once daily by gavage), the obesity phenotype and pharmacodynamic effects were evaluated by histopathological examination of epididymal fat, liver, and colon using hematoxylin-eosin staining and serum biochemical analyses by an automated chemistry analyzer. The feces were collected at the 12 th week, and taxonomic and functional profiles of gut microbiota were analyzed by 16S ribosomal ribonucleic acid (16S rRNA) sequencing.@*RESULTS@#Compared with HFD group, the average body weight of APS plus BBR group was decreased (P<0.01), accompanied with the reduced fat accumulation, enhanced colonic integrity, insulin sensitivity and glucose homeostasis (P<0.05 or P<0.01). Importantly, APS combined with BBR treatment was more effective than APS or BBR alone in improving HFD-induced insulin resistance (P<0.05 or P<0.01). 16S rRNA sequence-based analysis of fecal samples demonstrated that APS combined with BBR treatment exhibited a better impact on HFD-induced gut microbiota dysbiosis, exclusively via the enriched abundances of Bacteroides, which corresponded to the large increase of predicted bacterial genes involved in carbohydrate metabolism.@*CONCLUSION@#APS combined with BBR may synergistically reduce obesity and modulate the gut microbiota in HFD-fed mice.

Establishment and Optimization of MSAP Reaction System of Astragalus Mongolica / 世界科学技术-中医药现代化

Objective To study epigenetic diversity of Astragalus mongolicus by methylation-sensitive amplification polymorphism(MSAP)technique,and to establish and optimize the response system of MSAP technique applicable to Astragalus Mongolicus.Methods Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao was used as material.The single factor and orthogonal design method were used to optimize the key influencing factors of the reaction system of Astragalus Mongolian methylation-sensitive amplification polymorphism(MSAP)technique,and the best reaction system of Astragalus Mongolian MSAP was established.Results 0.5 μL each of EcoR I and Msp I/Hpa II were added to the 20 μL double-enzyme digestion reaction system,and the digestion was completed in a water bath at 37℃for 6 h to complete the digestion;the optimal ligation system was 25 μL,including 10 μL digestion product,0.2 μL T4 DNA Ligase,1 μL EcoR I-adapter,1 μL Hpa II/Msp I-adapter,2.5 μL 10×T4 Buffer;25 μL optimal pre-amplification reaction system,including 2.5 μL 10×PCR buffer,0.5 μL dNTP,2.0 μL ligation product,0.3 μL Taq DNA polymerase,1.0 μL upstream and downstream primers;25 μL optimal selective amplification system,including 2 μL 20-fold diluted pre-amplification product,1.0 μL 10×PCR buffer,1.0 μL dNTP,0.2 μL Taq DNA polymerase,0.8 μL primers.Conclusion The optimized MSAP system was detected by polyacrylamide gel electrophoresis,which showed that the polymorphism was good,the system was stable,the bands were clear and repeatable,which laid the foundation for the subsequent MSAP analysis of Astragalus mongolica.

Inhibitory effect of astragalus membranaceus injection on apoptosis and autophagy induced by enterovirus 71 / 中国生物制品学杂志

@#Objective To investigate the effect of astragalus membranaceus（AM）injection on apoptosis and autophagy of human gastric epithelial cell line（GES⁃1）induced by enterovirus 71（EV71）. Methods GES⁃1 cells were cultured in vitro and divided into infected group（EV71 infected at a MOI of 3 and control group（no virus infected）. The morpho⁃logical changes of EV71 infected cells were observed by inverted microscope. The level of VP1 in GES⁃1 cells infected with EV71 was detected by Western blot；CCK⁃8 assay was used to detect the viability of GES⁃1 cells infected with EV71；Nuclear staining with DAPI was used to observe the morphological changes of nuclear apoptosis infected with EV71. GES⁃1 cells were divided into control group（without virus infection），infection group and AM intervention group with final concentration of 1，2. 5，5 and 10 μg／mL，respectively. Western blot was used to detect the effect of AM intervention on the expression of apoptosis⁃related proteins Caspase⁃3，PARP and autophagy⁃related proteins LC3 and P62 in GES⁃1 cells infected withEV71. CCK⁃8 method was used to detect the effect of AM intervention on the viability of GES⁃1 cells infected with EV71. Results GES⁃1 cells were round，shrunken with nuclear pyknosis and uneven size；VP1 level increased（t = 41. 56，P < 0. 01），cell viability decreased（t = 19. 07，P < 0. 01），Caspase⁃3 and PARP proteins were cut off（t = 35. 29 and 3. 648， P < 0. 01 and 0. 021 8，respectively），LC3Ⅱ／LC3Ⅰ ratio increased（t = 10. 16，P = 0. 000 5）and P62 protein was degraded（t = 68. 68，P < 0. 01）；AM inhibited the degradation of Caspase⁃3，PARP and P62 proteins induced by EV71 （t = 52. 66，59. 60 and 40. 22，respectively，each P < 0. 01）and increased the ratio of LC3Ⅱ／LC3Ⅰ（t = 5. 521，P = 0. 005 3），andreducedtheinhibitoryeffectofEV71ontheviabilityofGES⁃1cells（t =4. 420，P =0. 0115）. Conclusion EV71 infection induced apoptosis of GES⁃ 1 cells and AM intervention inhibited EV71 induced apoptosis by inhibiting EV71 induced autophagy.

Preparation and polarization activity research of astragalus polysaccharide-superparamagnetic iron oxide nanocomposite / 药学学报

Size and surface modification are the two key factors affecting the effect of macrophages polarization induced by superparamagnetic iron oxide nanoparticles (SPIONs). The smaller the particle size, the better the polarization effect of SPIONs. Besides, the reasonable SPIONs surface modification method can also be used to enhance the polarization effect. In this study, SPIONs was prepared by solvothermal method and optimized by Box-Benhnken center combination design and response surface method. Furthermore, astragalus polysaccharide-superparamagnetic iron oxide nanocomplex (APS-SPIONs) was successfully constructed by EDC/NHS esterification method. The structure of APS-SPIONs was confirmed by dynamic light scatter and infrared spectrometer, and the contents of iron and polysaccharide were characterized by spectrophotometry. The effect of APS-SPIONs on inducing mouse macrophages RAW264.7 polarization was investigated by flow cytometry. The RAW264.7 macrophages-HepG2 human hepatoma cancer cells Transwell co-culture system was established to investigate APS-SPIONs improve anti-tumor function of macrophages in vitro, and the proliferation activity of APS-SPIONs on RAW264.7 detected by cell counting kit-8 (CCK-8) method. The results showed that the average particle size and zeta potential of APS-SPIONs were (82.93 ± 1.47) nm and (-24.00 ± 0.47) mV. Polysaccharide and Fe content were 8.69% and 7.04%, respectively. APS-SPIONs effectively induced the polarization of RAW264.7 into M1 type in vitro, improving the anti-tumor ability of macrophages in a co-culture system, without effecting the proliferation of macrophages. Our study provides a drug development strategy and preliminary research results to educate macrophages and reshape the tumor immune microenvironment to achieve tumor-killing effects.

Optimization of extraction technology for couplet medicinals of Astragalus membranaceus-Puerariae lobata by multi-index comprehensive scoring method combined with orthogonal experiment / 中国药房

OBJECTIVE To optimize extraction technology of couplet medicinals of Astragalus membranaceus-Puerariae lobatae. METHODS With contents of puerarin，daidzin，calycosin-7-O-β-D-glucopyranoside，daidzein，calycosin and formononetin and the yield of dry extract as index，the analytic hierarchy method was used to determine the weight coefficient of each index and calculate the comprehensive score. The effects of solid-liquid ratio， extraction times and extraction time on the comprehensive score were investigated by single factor test. The level of each factor was determined. By multi-index comprehensive scoring method， using comprehensive scores of above 7 indexes as indexes，the extraction technology of couplet medicinals of A. membranaceus-P. lobata was optimized by orthogonal experiment，and the validation tests were conducted. RESULTS The weight coefficient for the contents of puerarin，daidzin，calycosin-7-O-β-D-glucopyranoside，daidzein，calycosin and formononetin and the yield of dry extract were respectively 0.304 7，0.065 2，0.185 8，0.185 8，0.107 8，0.107 8 and 0.042 7. The optimal extraction technology was determined as follows： solid-liquid of 1∶8（g/mL），extracting 3 times and for 1 h each time. RSD of each evaluation index in the validation test results was lower than 3.00% （n＝3）. CONCLUSIONS The optimized extraction technology for A. membranaceus-P. lobata is stable and feasible.

Research progress of effective components of Astragalus on prevention and treatment of organ fibrosis / 药学学报

Astragalus, which was first documented in Shennong Bencao Jing, is the dried root of Astragalus membranaceus (Fisch.) Bge. or Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao. The active ingredients astragalus membranaceus saponins (AMS), astragalus polysaccharides (APS) and astragalus flavonoids (AFS) have pharmacological effects such as anti-tumor properties, lowering blood sugar, regulating lipid metabolism, cardiovascular protection, anti-oxidation, bone protection, anti-fibrosis, etc. Fibrosis affects almost all organs, particularly vital organs such as the lungs, liver, heart and kidneys. The primary pathological changes of fibrosis involve abnormal increase of myofibroblasts and excessive deposition of extracellular matrix (ECM) components, which lead to the formation of scar tissue, ultimately resulting in fibrosis and even functional loss or failure of organs, which seriously threatens human health and life. Recent, studies have shown that Astragalus membranaceus has a good therapetuic effect on organ fibrosis. This article reviews the current advances of Astragalus in the prevention and treatment of fibrosis of lungs, liver, heart, kidneys and other important organs.

Progress in Mechanism of Astragalus membranaceus and Its Chemical Constituents on Multiple Sclerosis / 中国结合医学杂志

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.

Astragalus polysaccharide inhibits IDO1 expression in colon tumor microenvironment to increase intratumoral CD8~+ T cell infiltration / 中国中药杂志

This study aims to investigate the regulatory effects of Astragalus polysaccharide(APS) and APS combined with 5-fluorouracil(5-FU) on indoleamine-2,3-dioxygenase(IDO1) in the colon tumor microenvironment. Sixty Balb/c mice were randomized into a blank group, a model group, an APS group, an APS + 5-FU group, an APS + low-dose 5-FU group, and a 5-FU group. A tumor model was established by subcutaneous transplantation with CT-26 mouse colon cancer cells in other groups except the blank group. After successful modeling, each group was treated with corresponding drugs for 7 days. The general condition, body weight, and tumor volume of the mice were observed and measured daily during the treatment period. The mice were sacrificed at the end of treatment, and the tumor suppression rate and spleen index of the mice were calculated. Western blot and fluorescence quantitative PCR were employed to determine the protein and mRNA levels, respectively, of IDO1 in the tumor tissue of mice. High performance liquid chromatography was employed to measure the levels of tryptophan(Trp) and kynurenine(Kyn) in the tumor tissue of mice. Hematoxylin-eosin(HE) staining was performed to observe the histological changes of the tumor tissue, and immunohistochemistry to detect the changes of CD4 and CD8 expression in the tumor tissue. Compared with that in the model group, the tumor volume of mice in each treatment group significantly reduced. The body weights of mice in APS + 5-FU group and 5-FU group significantly reduced from day 4 to day 7 of treatment. In addition, the APS + 5-FU group and 5-FU group showed significantly decreased spleen index. The protein and mRNA levels of IDO1 were significantly down-regulated in the APS, APS + 5-FU, and APS + low-dose 5-FU groups. The drug interventions significantly increased the Trp content and decreased the Kyn content. The APS + 5-FU group showed significantly reduced infiltration of CD4~+ T lymphocytes and increased infiltration of CD8~+ T lymphocytes. APS inhibited the expression of IDO1 in the colon tumor microenvironment to increase CD8~+ T lymphocyte infiltration, and the combination of APS with 5-FU demonstrated better effect.

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.

Modulating effects of Astragalus polysaccharide on immune disorders via gut microbiota and the TLR4/NF-κB pathway in rats with syndrome of dampness stagnancy due to spleen deficiency / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The syndrome of dampness stagnancy due to spleen deficiency (DSSD) is relatively common globally. Although the pathogenesis of DSSD remains unclear, evidence has suggested that the gut microbiota might play a significant role. Radix Astragali, used as both medicine and food, exerts the effects of tonifying spleen and qi. Astragalus polysaccharide (APS) comprises a macromolecule substance extracted from the dried root of Radix Astragali, which has many pharmacological functions. However, whether APS mitigates the immune disorders underlying the DSSD syndrome via regulating gut microbiota and the relevant mechanism remains unknown. Here, we used DSSD rats induced by high-fat and low-protein (HFLP) diet plus exhaustive swimming, and found that APS of moderate molecular weight increased the body weight gain and immune organ indexes, decreased the levels of interleukin-1β (IL-1β), IL-6, and endotoxin, and suppressed the Toll-like receptor 4/nuclear factor-‍κB (TLR4/NF-‍κB) pathway. Moreover, a total of 27 critical genera were significantly enriched according to the linear discriminant analysis effect size (LEfSe). APS increased the diversity of the gut microbiota and changed its composition, such as reducing the relative abundance of Pseudoflavonifractor and Paraprevotella, and increasing that of Parasutterella, Parabacteroides, Clostridium XIVb, Oscillibacter, Butyricicoccus, and Dorea. APS also elevated the contents of short-chain fatty acids (SCFAs). Furthermore, the correlation analysis indicated that 12 critical bacteria were related to the body weight gain and immune organ indexes. In general, our study demonstrated that APS ameliorated the immune disorders in DSSD rats via modulating their gut microbiota, especially for some bacteria involving immune and inflammatory response and SCFA production, as well as the TLR4/NF-κB pathway. This study provides an insight into the function of APS as a unique potential prebiotic through exerting systemic activities in treating DSSD.