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1.
Mol Biol Rep ; 51(1): 618, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38705956

ABSTRACT

BACKGROUND: Astragalus membranaceus is a plant of the Astragalus genus, which is used as a traditional Chinese herbal medicine with extremely high medicinal and edible value. Astragalus mongholicus, as one of the representative medicinal materials with the same origin of medicine and food, has a rising market demand for its raw materials, but the quality is different in different production areas. Growth-regulating factors (GRF) are transcription factors unique to plants that play important roles in plant growth and development. Up to now, there is no report about GRF in A. mongholicus. METHODS AND RESULTS: This study conducted a genome-wide analysis of the AmGRF gene family, identifying a total of nine AmGRF genes that were classified into subfamily V based on phylogenetic relationships. In the promoter region of the AmGRF gene, we successfully predicted cis-elements that respond to abiotic stress, growth, development, and hormone production in plants. Based on transcriptomic data and real-time quantitative polymerase chain reaction (qPCR) validation, the results showed that AmGRFs were expressed in the roots, stems, and leaves, with overall higher expression in leaves, higher expression of AmGRF1 and AmGRF8 in roots, and high expression levels of AmGRF1 and AmGRF9 in stems. CONCLUSIONS: The results of this study provide a theoretical basis for the further exploration of the functions of AmGRFs in plant growth and development.


Subject(s)
Gene Expression Regulation, Plant , Phylogeny , Plant Proteins , Transcription Factors , Gene Expression Regulation, Plant/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Astragalus propinquus/genetics , Astragalus propinquus/metabolism , Multigene Family , Genome, Plant , Gene Expression Profiling/methods , Promoter Regions, Genetic/genetics , Astragalus Plant/genetics , Astragalus Plant/metabolism , Plant Roots/genetics , Plant Roots/metabolism , Stress, Physiological/genetics , Transcriptome/genetics , Plant Growth Regulators/metabolism
2.
Plant Signal Behav ; 19(1): 2355740, 2024 Dec 31.
Article in English | MEDLINE | ID: mdl-38776425

ABSTRACT

During plant growth and development, the YABBY gene plays a crucial role in the morphological structure, hormone signaling, stress resistance, crop breeding, and agricultural production of plant lateral organs, leaves, flowers, and fruits. Astragalus mongholicus is a perennial herbaceous plant in the legume family, widely used worldwide due to its high medicinal and edible value. However, there have been no reports of the YABBY gene family in A. mongholicus. This study used bioinformatics methods, combined with databases and analysis websites, to systematically analyze the AmYABBY gene family in the entire genome of A. mongholicus and verified its expression patterns in different tissues of A. mongholicus through transcriptome data and qRT-PCR experiments. A total of seven AmYABBY genes were identified, which can be divided into five subfamilies and distributed on three chromosomes. Two pairs of AmYABBY genes may be involved in fragment duplication on three chromosomes. All AmYABBY proteins have a zinc finger YABBY domain, and members of the same group have similar motif composition and intron - exon structure. In the promoter region of the genes, light-responsive and MeJa-response cis-elements are dominant. AmYABBY is highly expressed in stems and leaves, especially AmYABBY1, AmYABBY2, and AmYABBY3, which play important roles in the growth and development of stems and leaves. The AmYABBY gene family regulates the growth and development of A. mongholicus. In summary, this study provides a theoretical basis for in-depth research on the function of the AmYABBY gene and new insights into the molecular response mechanism of the growth and development of the traditional Chinese medicine A. mongholicus.


Subject(s)
Astragalus Plant , Gene Expression Regulation, Plant , Plant Proteins , Plant Proteins/genetics , Plant Proteins/metabolism , Astragalus Plant/genetics , Astragalus Plant/metabolism , Genome, Plant/genetics , Multigene Family , Phylogeny , Genes, Plant , Promoter Regions, Genetic/genetics
3.
Plant Physiol ; 193(3): 2164-2179, 2023 Oct 26.
Article in English | MEDLINE | ID: mdl-37610417

ABSTRACT

The lipid transport protein (LTP) product of the AsE246 gene of Chinese milk vetch (Astragalus sinicus) contributes to the transport of plant-synthesized lipids to the symbiosome membranes (SMs) that are required for nodule organogenesis in this legume. However, the mechanisms used by nodule-specific LTPs remain unknown. In this study, a functional protein in the DnaJ-like family, designated AsDJL1, was identified and shown to interact with AsE246. Immunofluorescence showed that AsDJL1 was expressed in infection threads (ITs) and in nodule cells and that it co-localized with rhizobium, and an immunoelectron microscopy assay localized the protein to SMs. Via co-transformation into Nicotiana benthamiana cells, AsDJL1 and AsE246 displayed subcellular co-localization in the cells of this heterologous host. Co-immunoprecipitation assays confirmed that AsDJL1 interacted with AsE246 in nodules. The essential interacting region of AsDJL1 was determined to be the zinc finger domain at its C-terminus. Chinese milk vetch plants transfected with AsDJL1-RNAi had significantly decreased numbers of ITs, nodule primordia and nodules as well as reduced (by 83%) nodule nitrogenase activity compared with the controls. By contrast, AsDJL1 overexpression led to increased nodule fresh weight and nitrogenase activity. RNAi-AsDJL1 also significantly affected the abundance of lipids, especially digalactosyldiacylglycerol, in early-infected roots and transgenic nodules. Taken together, the results of this study provide insights into the symbiotic functions of AsDJL1, which may participate in lipid transport to SMs and play an essential role in rhizobial infection and nodule organogenesis.


Subject(s)
Astragalus Plant , Fabaceae , Rhizobium , Nitrogen Fixation/genetics , Root Nodules, Plant/genetics , Root Nodules, Plant/metabolism , Carrier Proteins/metabolism , Astragalus Plant/metabolism , Nitrogenase/metabolism , Lipids , Symbiosis/genetics , Plant Root Nodulation , Plant Proteins/genetics , Plant Proteins/metabolism
4.
Genes (Basel) ; 14(7)2023 07 05.
Article in English | MEDLINE | ID: mdl-37510305

ABSTRACT

Astragalus sinicus is an important winter-growing cover crop. It is widely utilized, not only as a cover crop for its benefits in fertilizing the soil but also as a landscape ground cover plant. Anthocyanins are involved in the pigmentation of plants in leaves and flowers, which is a crucial characteristic trait for A. sinicus. The formation of anthocyanins depends significantly on the enzyme chalcone isomerase (CHI). However, research on the CHI gene of A. sinicus remains unexplored. The rapid amplification of cDNA ends (RACE) approach was used in this research to clone the CHI sequence from A. sinicus (AsiCHI). The expression profiles of the AsiCHI gene in multiple tissues of A. sinicus were subsequently examined by qRT-PCR (Quantitative Real-Time PCR). Furthermore, the function of the AsiCHI was identified by the performance of ectopic expression in Arabidopsis (Arabidopsis thaliana). The outcomes revealed that the full-length cDNA of the AsiCHI gene (GeneBank: OQ870547) measured 972 bp in length and included an open reading frame of 660 bp. The encoded protein contains 219 amino acids with a molecular weight of 24.14 kDa and a theoretical isoelectric point of 5.11. In addition, the remarkable similarity between the AsiCHI protein and the CHI proteins of other Astragalus species was demonstrated by the sequence alignment and phylogenetic analysis. Moreover, the highest expression level of AsiCHI was observed in leaves and showed a positive correlation with anthocyanin content. The functional analysis further revealed that the overexpression of AsiCHI enhanced the anthocyanidin accumulation in the transgenic lines. This study provided a better understanding of AsiCHI and elucidated its role in anthocyanin production.


Subject(s)
Anthocyanins , Astragalus Plant , Anthocyanins/metabolism , Cloning, Molecular , DNA, Complementary/genetics , Phylogeny , Real-Time Polymerase Chain Reaction , Astragalus Plant/genetics , Astragalus Plant/metabolism
5.
J Zhejiang Univ Sci B ; 24(7): 650-662, 2023 Jul 15.
Article in English, Chinese | MEDLINE | ID: mdl-37455140

ABSTRACT

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-1ß (IL-1ß), 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.


Subject(s)
Astragalus Plant , Gastrointestinal Microbiome , Immune System Diseases , Rats , Animals , NF-kappa B/metabolism , Spleen , Toll-Like Receptor 4 , Polysaccharides/pharmacology , Astragalus Plant/metabolism , Immune System Diseases/drug therapy , Body Weight
6.
Iran J Allergy Asthma Immunol ; 22(2): 172-182, 2023 Apr 30.
Article in English | MEDLINE | ID: mdl-37496410

ABSTRACT

Astragalus polysaccharide (APS) is a functional component of Astragalus membranaceus with antitumor and immunomodulatory properties. This study evaluated the effect of APS on the peripheral blood mononuclear cell (PBMC) proliferation, cytokine secretion, and regulatory T cell (Treg) induction in an in vitro coculture model of human PBMCs and A2780 human ovarian cancer cells. PBMC proliferation and Treg frequency were measured by flow cytometry. Cytokine levels were assessed by enzyme-linked immunosorbent assay. APS significantly enhanced the PBMC proliferation, reduced Treg frequency, decreased anti-inflammatory cytokines including interleukin [IL]-10, transforming growth factor beta (TGF-ß), and vascular endothelial growth factor-A (VEGF-A), and increased the pro-inflammatory cytokine IL-6. These findings suggest that APS may be an effective immunomodulatory supplement for cancer therapy, particularly for ovarian cancer by enhancing antitumor immune responses.


Subject(s)
Astragalus Plant , Ovarian Neoplasms , Humans , Female , Leukocytes, Mononuclear/metabolism , Vascular Endothelial Growth Factor A , Cell Line, Tumor , Ovarian Neoplasms/drug therapy , Astragalus Plant/metabolism , Polysaccharides/pharmacology , Cytokines/metabolism , Immunity
7.
Article in English | WPRIM (Western Pacific) | ID: wpr-982405

ABSTRACT

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.


Subject(s)
Rats , Animals , NF-kappa B/metabolism , Spleen , Gastrointestinal Microbiome , Toll-Like Receptor 4 , Polysaccharides/pharmacology , Astragalus Plant/metabolism , Immune System Diseases/drug therapy , Body Weight
8.
Sci Rep ; 12(1): 11884, 2022 07 13.
Article in English | MEDLINE | ID: mdl-35831335

ABSTRACT

Liver cirrhosis is a late-stage liver disease characterized by excessive fibrous deposition triggering portal-hypertension (PH); the prime restrainer for cirrhosis-related complications. Remedies that can dually oppose hepatic fibrosis and lower PH, may prevent progression into decompensated-cirrhosis. Different Astragalus-species members have shown antifibrotic and diuretic actions with possible subsequent PH reduction. However, A.spinosus and A.trigonus were poorly tested for eliciting these actions. Herein, A.spinosus and A.trigonus roots and aerial parts extracts were subjected to comprehensive metabolic-fingerprinting using UHPLC-MS/MS resulting in 56 identified phytoconstituents, followed by chemometric untargeted analysis that revealed variable metabolic profiles exemplified by different species and organ types. Consequently, tested extracts were in-vivo evaluated for potential antifibrotic/anticirrhotic activity by assessing specific markers. The mechanistic prospective to induce diuresis was investigated by analyzing plasma aldosterone and renal-transporters gene-expression. Serum apelin and dimethylarginine-dimethylaminohydrolase-1 were measured to indicate the overall effect on PH. All extracts amended cirrhosis and PH to varying extents and induced diuresis via different mechanisms. Further, An OPLS model was built to generate a comprehensive metabolic-profiling of A.spinosus and A.trigonus secondary-metabolites providing a chemical-based evidence for their efficacious consistency. In conclusion, A.spinosus and A.trigonus organs comprised myriad pharmacologically-active constituents that act synergistically to ameliorate cirrhosis and associated PH.


Subject(s)
Astragalus Plant , Hypertension, Portal , Liver Cirrhosis , Plant Extracts , Aldosterone/blood , Amidohydrolases/blood , Apelin/blood , Astragalus Plant/chemistry , Astragalus Plant/metabolism , Chromatography, High Pressure Liquid , Diuresis , Hydrogen-Ion Concentration , Hypertension, Portal/blood , Hypertension, Portal/drug therapy , Hypertension, Portal/etiology , Hypertension, Portal/metabolism , Liver/metabolism , Liver Cirrhosis/blood , Liver Cirrhosis/complications , Liver Cirrhosis/drug therapy , Liver Cirrhosis/metabolism , Metabolome/drug effects , Phytochemicals/chemistry , Phytochemicals/metabolism , Phytochemicals/pharmacology , Phytochemicals/therapeutic use , Plant Extracts/chemistry , Plant Extracts/metabolism , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Prospective Studies , Tandem Mass Spectrometry
9.
Zhongguo Zhong Yao Za Zhi ; 47(13): 3463-3474, 2022 Jul.
Article in Chinese | MEDLINE | ID: mdl-35850797

ABSTRACT

The difference of astragaloside Ⅳ content and the expression of its biosynthesis related genes in imitating wild Astragalus mongolicus(IWA) and cultivated A.mongolicus(CA) under different growth years were systematically compared and analyzed.Then the key enzyme genes affected the difference of astragaloside Ⅳ content in the above two A.mongolicus were screened.High-perfo-rmance liquid chromatography(HPLC)was used to determine the content of astragaloside Ⅳ in A.mongolicusunderthe above two diffe-rent growth patterns.Based on the Illumina HiSeq and PacBio high-throughput sequencing platforms, thesecond-and third-generation transcriptome sequencing(RNA-Seq)databaseof the two A.mongolicuswas constructed.The related enzyme genes in the biosynthetic pathway of astragaloside Ⅳ were screened and verified byquantitative reverse transcriptase polymerase chain reaction(RT-qPCR).The RNA-sequencing(RNA-Seq) and RT-qPCR data of each gene were subjected to correlation analysis and trend analysis.The results showed that the variation trend of astragaloside Ⅳ contentby HPLC wasthe same as that of genes by RNA-Seq and RT-qPCR in 1-4 year IWA and 1-2 year CA.The trend level of astragaloside Ⅳ contentwas lower in 2-year IWA than 1-year IWA.Compared with 2-year IWA, 3-year IWA had an upward trend, while 4-year IWA hada downward trend versus 3-year IWA.Additionally, 1-year CA had increased trendthan 2-year CA.However, the content of astragaloside Ⅳ in 5-year IWA was higher than that of 6-year IWA, which wasinconsistent with the findings of RNA-Seq and RT-qPCR.This study preliminarily clarifiedthat the difference of astragaloside Ⅳ contentin 1-4 year IWA and 1-2 year CA wasclosely related to the expression of the upstream and midstream genes(MVK, CMK, PMK, MVD, SS) in the biosynthetic pathway.The results facilitate the production and planting of Radix Astragali seu Hedysari.


Subject(s)
Astragalus Plant , Saponins , Triterpenes , Astragalus Plant/genetics , Astragalus Plant/metabolism , Astragalus propinquus/genetics , Saponins/analysis , Saponins/genetics , Triterpenes/analysis
10.
J Trace Elem Med Biol ; 73: 127006, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35660560

ABSTRACT

BACKGROUND: Astragalus Polysaccharides (APS) had been reported to exhibit antitumor activities. Given that nanoparticles possessed unique advantages in cancer treatment, APS was used as the modifier to prepare gold, silver and selenium nanoparticles (APS-Au, APS-Ag and APS-Se NPs) in the present study. METHODS: The three nanoparticles were synthesized via a green approach and characterized by DLS, TEM, XRD, FT-IR and UV-Vis. The inhibitory effects of these nanoparticles on various tumor cells proliferation were examined by MTT assay in vitro. Reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and the expression of apoptosis and autophagy-related proteins were also detected. RESULTS: Among these, APS-Se NPs displayed the most potent antitumor activities against MCF-7 cells in vitro. Flow cytometric analysis suggested that after cells were exposed to elevated concentrations of APS-Se NPs (10, 20 and 40 µmol/L), the rate of apoptosis was increasing (16.63 ± 0.89, 38.60 ± 3.46 and 44.38 ± 2.62%, respectively). Further analysis by immunofluorescence revealed an increase in intracellular ROS and a loss of MMP. This was accompanied by increased LC3-I to LC3-II conversion. Also, western blot analysis demonstrated that the ratios of Bax/Bcl-2 and cleaved caspase9/caspase 9 rose, and LC3-II and p62 protein levels increased. The addition of chloroquine, an inhibitor of autophagy, further enhanced protein expression of p62 and LC3-II. CONCLUSION: APS-Se NPs exerted their cytotoxic activity in MCF-7 cells by blocking autophagy and facilitating mitochondrial pathway-mediated apoptosis.


Subject(s)
Astragalus Plant , Nanoparticles , Selenium , Apoptosis , Astragalus Plant/metabolism , Autophagy , Humans , MCF-7 Cells , Polysaccharides/pharmacology , Reactive Oxygen Species/metabolism , Selenium/pharmacology , Spectroscopy, Fourier Transform Infrared
11.
Zhongguo Zhong Yao Za Zhi ; 47(10): 2738-2749, 2022 May.
Article in Chinese | MEDLINE | ID: mdl-35718494

ABSTRACT

This study aims to explore the mechanism of Astragali Radix-Puerariae Lobatae Radix(AP) combination in the treatment of type 2 diabetes mellitus(T2 DM) based on network pharmacology and experiment. The effective components and targets of the pair were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and targets of T2 DM from each disease database. On this basis, the common targets of the medicinals and the disease were screened out. The protein-protein interaction(PPI) network was established based on STRING. Then Cytoscape 3.7.1 was employed for visualization of the common targets and the network topology analysis of key targets, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of core targets by DAVID. Thereby, the possible molecular mechanism was unveiled. High-fat diet was combined with streptozotocin(STZ, injected into tail vein) for T2 DM rat modeling. Rats were classified into the normal group, model group, positive control group(metformin hydrochloride), AP high-dose, medium-dose, and low-dose groups. After 4 weeks of intragastric administration, serum fasting blood glucose(FBG), fasting insulin(FINS), aspartate aminotransferase(AST), alanine aminotransferase(ALT), triglyceride(TG), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), interleukin(IL)-6, and tumor necrosis factor(TNF)-α of rats in each group were measured. The expression of insulin receptor substrate-2(IRS-2), adenosine monophosphate-activated protein kinase(AMPK), phosphorylated AMPK(p-AMPK), glucose 6 phosphatase(G6 Pase), and phosphoenolpyruvate carboxy kinase(Pepck) in rat liver was detected by Western blot. A total of 131 core targets of the combination in the treatment of T2 DM were screened out, among which protein kinase B(AKT) 1, mitogen-activated protein kinase(MAPK) 1, TNF-α, IL-6 were more critical. KEGG enrichment analysis suggested that the combination decreased blood glucose mainly through PI3 K/AKT signaling pathway, AMPK signaling pathway, TNF signaling pathway, and MAPK signaling pathway. The levels of FBG and FINS were lower and the glycogen level was higher in the AP high-dose and medium-dose groups than in the model group. The levels of AST, ALT, TG, and LDL-C in the three AP groups and the level of TC in AP high-dose and low-dose groups decreased compared with those in the model group. Levels of IL-6 and TNF-α were lower in AP high-dose and medium-dose groups than in the model group. The expression of IRS-2, AMPK, and p-AMPK was higher and that of G6 Pase and Pepck was lower in AP high-dose group than in the model group. Thus, the combination had multi-component, multi-target, and multi-pathway characteristics in the treatment of T2 DM. It may regulate AMPK signaling pathway through IL-6 and TNF-α to influence insulin resistance, glycogen synthesis, gluconeogenesis, islet ß cell transport, and inflammatory response, thereby exerting therapeutic effect on T2 DM.


Subject(s)
Astragalus Plant , Diabetes Mellitus, Type 2 , Drugs, Chinese Herbal , Pueraria , AMP-Activated Protein Kinases/genetics , AMP-Activated Protein Kinases/metabolism , Animals , Astragalus Plant/metabolism , Blood Glucose/metabolism , Cholesterol, LDL/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Glycogen/therapeutic use , Interleukin-6/genetics , Network Pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Rats , Signal Transduction , Streptozocin/therapeutic use , Tumor Necrosis Factor-alpha
12.
Pharm Biol ; 60(1): 825-839, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35587259

ABSTRACT

CONTEXT: Post-sepsis cognitive impairment is one of the major sequelae observed in survivors of sepsis. Astragalus injection is the normally preferred treatment in sepsis in clinical settings. OBJECTIVE: This study evaluated the benefits and related mechanism of Astragalus injection on post-sepsis cognitive impairment. MATERIALS AND METHODS: C57BL/6J mice were divided into three groups: Control, LPS (2.5 mg/kg, i.p.), and LPS + Astragalus injection (5.0 mL/kg). The surviving mice from sepsis were injected with material named Astragalus injection continuously for 13 days. Behavioural tests were first conducted to evaluate the benefits. Second, inflammatory cytokines secretion, BBB integrity, neurodegeneration, and protein expression was evaluated in vivo and in vitro. RESULTS: Compared with the LPS group, mice in Astragalus injection group exhibited shorter escape latency (34.6 s versus 24.5 s) in the Morris water maze test. Treatment with Astragalus injection could reverse LPS-induced neuroinflammation in mice and BV2 cells. Continuous Astragalus injection treatment not only prevented blood-brain barrier dysfunction, but also prevented neurodegeneration. Further molecular docking tests and western blot results reflected that the main constituents of Astragalus injection could interact with TrkB (the estimated binding energy values were -7.0 to -5.0 kcal/mol) and upregulate the protein expression of BDNF/TrkB/CREB signalling pathway during the chronic stage in mice. DISCUSSION: Astragalus injection treatment could reduce neuroinflammation, reverse BBB dysfunction, prevent neurodegeneration, and upregulate BDNF-CREB pathway during LPS-induced sepsis, ultimately preventing the development of cognitive decline. CONCLUSION: Astragalus injection could be a potential preventive and therapeutic strategy for sepsis survivors in clinical settings.


Subject(s)
Astragalus Plant , Cognitive Dysfunction , Sepsis , Animals , Astragalus Plant/metabolism , Blood-Brain Barrier/metabolism , Brain-Derived Neurotrophic Factor/metabolism , Cognitive Dysfunction/drug therapy , Lipopolysaccharides/toxicity , Mice , Mice, Inbred C57BL , Molecular Docking Simulation , Neuroinflammatory Diseases , Sepsis/chemically induced , Sepsis/complications , Sepsis/drug therapy
13.
Cell Biochem Biophys ; 80(2): 341-353, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35107747

ABSTRACT

Vascular endothelial cells play a vital role in atherosclerotic changes and the progression of cardiovascular disease in older adults. Previous studies have indicated that Astragalus polysaccharides (APS), a main active component of the traditional Chinese medicine Astragalus, protect mitochondria and exert an antiaging effect in the mouse liver and brain. However, the effect of APS on rat aortic endothelial cell (RAEC) senescence and its underlying mechanism have not been investigated. In this study, we extracted RAECs from 2-month-old male Wistar rats by the tissue explant method and found that APS ameliorated the high-glucose-induced increase in the frequency of SA-ß-Gal positivity and the levels of the senescence-related proteins p16, p21, and p53. APS increased the tube formation capacity of RAECs under high-glucose conditions. Moreover, APS enhanced the expression of the mitochondrial Na+/Ca2+ exchanger NCLX, and knockdown of NCLX by small interfering RNA (siRNA) transfection suppressed the antiaging effect of APS under high-glucose conditions. Additionally, APS ameliorated RAEC mitochondrial dysfunction, including increasing ATP production, cytochrome C oxidase activity and the oxygen consumption rate (OCR), and inhibited high-glucose-induced NLRP3 inflammasome activation and IL-1ß release, which were reversed by siNCLX. These results indicate that APS reduces high-glucose-induced inflammasome activation and ameliorates mitochondrial dysfunction and senescence in RAECs by modulating NCLX. Additionally, APS enhanced the levels of autophagy-related proteins (LC3B-II/I, Atg7) and increased the quantity of autophagic vacuoles under high-glucose conditions. Therefore, these data demonstrate that APS may reduce vascular endothelial cell inflammation and senescence through NCLX.


Subject(s)
Astragalus Plant , Inflammasomes , Animals , Astragalus Plant/metabolism , Endothelial Cells/metabolism , Glucose/metabolism , Inflammasomes/metabolism , Inflammasomes/pharmacology , Male , Mice , Mitochondria/metabolism , Polysaccharides/pharmacology , RNA, Small Interfering/metabolism , Rats , Rats, Wistar , Sodium-Calcium Exchanger/metabolism
14.
Kaohsiung J Med Sci ; 38(5): 457-468, 2022 May.
Article in English | MEDLINE | ID: mdl-34962345

ABSTRACT

Aging is characterized by inevitable organ function decline over time, with consequent body deterioration and increased susceptibility to death. Astragalus polysaccharide (APS) has been reported to have anti-oxidative, anti-apoptotic, and anti-inflammatory properties. We investigated the potential protective effects of APS on hydrogen peroxide (H2 O2 ) induced hepatocyte senescence and identified related mechanisms in L02, Huh7, and LM3 cell lines. Aged female C57BL/6 mice were given APS for 1 week by intraperitoneal injection, and APS provided the strongest protective effect against H2 O2 -induced damage at 100 µM. APS reduced the expression of cell senescence markers and alleviated pathological damage in aged mouse liver. APS treatment decreased oxidative stress, apoptosis, NOD-like receptor protein-3-mediated pyroptosis, and maintained mitochondrial homeostasis. Notably, the protective effect of APS was weakened in the presence of chloroquine. APS might enrich autophagy by activating AMP-activated protein kinase (AMPK) and inhibiting mammalian target of rapamycin (mTOR). In conclusion, APS reduced reactive oxygen species levels, inhibited apoptosis and pyroptosis, and promoted mitophagy via AMPK/mTOR pathway to alleviate hepatocyte senescence in vitro and in vivo.


Subject(s)
AMP-Activated Protein Kinases , Astragalus Plant , AMP-Activated Protein Kinases/genetics , AMP-Activated Protein Kinases/metabolism , Animals , Apoptosis , Astragalus Plant/metabolism , Autophagy , Hepatocytes/metabolism , Mammals/metabolism , Mice , Mice, Inbred C57BL , Polysaccharides/pharmacology , Signal Transduction , TOR Serine-Threonine Kinases/genetics , TOR Serine-Threonine Kinases/metabolism
15.
Nutrients ; 13(8)2021 Jul 27.
Article in English | MEDLINE | ID: mdl-34444724

ABSTRACT

Astragalus root (Huang Qi) and Shiitake mushrooms (Lentinus edodes) are both considered medicinal foods and are frequently used in traditional Chinese medicine due to their anticancer and immunomodulating properties. Here, the scientific literatures describing evidence for the anticancer and immunogenic properties of Shiitake and Astragalus were reviewed. Based on our experimental data, the potential to develop medicinal food with combined bioactivities was assessed using Shiitake mushrooms grown over Astragalus beds in a proprietary manufacturing process, as a novel cancer prevention approach. Notably, our data suggest that this new manufacturing process can result in transfer and increased bioavailability of Astragalus polysaccharides with therapeutic potential into edible Shiitake. Further research efforts are required to validate the therapeutic potential of this new Hengshan Astragalus Shiitake medicinal food.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Astragalus Plant , Functional Food , Immunomodulation , Neoplasms/therapy , Shiitake Mushrooms , Animals , Antineoplastic Agents, Phytogenic/therapeutic use , Antineoplastic Combined Chemotherapy Protocols , Astragalus Plant/chemistry , Astragalus Plant/growth & development , Astragalus Plant/metabolism , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Humans , Metabolomics , Neoplasms/drug therapy , Neoplasms/immunology , Phytotherapy , Shiitake Mushrooms/chemistry , Shiitake Mushrooms/growth & development , Shiitake Mushrooms/metabolism , Tumor Microenvironment
16.
Biomed Res Int ; 2021: 9976079, 2021.
Article in English | MEDLINE | ID: mdl-34258286

ABSTRACT

Vaccination has been identified as one of the most effective ways to prevent the transmission of infectious diseases in humans and animals. One of the most critical steps in vaccine development is the selection of a suitable adjuvant. Although various adjuvant candidates have been evaluated in the past few decades, only a limited amount of them are nontoxic and safe for human use. Astragalus polysaccharide (APS), due to its lack of toxicity, has been used as an immunomodulator to enhance immune responses. On the other hand, the immune effects of APS on ovalbumin are yet to be examined. Thus, in this study, we analyzed APS's effects on the immune response to ovalbumin in BALB/c mice. We have also used the classic adjuvant CpG oligodeoxynucleotide as the positive control.


Subject(s)
Antigens/chemistry , Astragalus Plant/metabolism , Ovalbumin/chemistry , Polysaccharides/chemistry , Polysaccharides/metabolism , Adjuvants, Immunologic , Animals , Cell Proliferation , CpG Islands , Female , Flow Cytometry , Immune System , Immunologic Factors/pharmacology , Mice , Mice, Inbred BALB C , Oligodeoxyribonucleotides , Spleen/cytology , Th1 Cells/immunology , Th2 Cells/immunology
17.
Bioprocess Biosyst Eng ; 44(8): 1793-1803, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33786675

ABSTRACT

20% (w/w) Astragali radix was added to the rice medium to cultivate C. kyushuensis Kob. The fermentation product was collected at mycelium stage, coloring stage, stromata-forming initial stage and fruiting body stage of C. kyushuensis Kob. The dynamic content changes of cordycepin and adenosine were detected at different fermentation stages. In the rice medium with Astragalus radix, both cordycepin and adenosine reached the highest content value on the 30th day of fermentation, 17.31 mg/g and 0.94 mg/g, respectively, which were 8.6 times and 2.0 times of that in rice medium at the same stage. At the same time, transcriptomics technology was used to analyze C. kyushuensis Kob during these four periods.


Subject(s)
Adenosine/chemistry , Astragalus Plant/microbiology , Cordyceps/metabolism , Deoxyadenosines/chemistry , Fermentation , Astragalus Plant/metabolism , Biotechnology/methods , Chromatography, High Pressure Liquid , Culture Media , Gene Expression Profiling , Gene Expression Regulation, Fungal , Mycelium , Oryza , RNA/metabolism , Transcriptome
18.
J Sci Food Agric ; 101(1): 82-90, 2021 Jan 15.
Article in English | MEDLINE | ID: mdl-32608134

ABSTRACT

BACKGROUND: Early weaning in yak calves is being attempted to improve yak reproduction rate. However, this has to be done with caution because of the high mortality rate of calves due to the lack of nutrients and the harsh environmental conditions. Twenty-four weaned male yak calves were used in a 60 day feeding trial in which astragalus root extract (ARE) was supplemented. They were assigned randomly to one of four dietary treatments (n = six per treatment) that differed in ARE level: 0 g kg-1 (control), ARE0 ; 20 g kg-1 , ARE20 ; 50 g kg-1 , ARE50; and 80 g kg-1 dry matter intake (DMI), ARE80 . RESULTS: Final bodyweight and average daily gain (ADG) were significantly higher and the DMI/ADG ratio was significantly lower in calves with ARE supplementation than control (ARE0 ) calves. Ruminal concentrations of acetate and propionate and serum concentration of superoxide dismutase in ARE80 calves were higher than in the other groups and serum concentration of insulin was higher in ARE80 calves than in ARE20 calves. Serum immunoglobulin G (IgG) and interleukin-2 (IL-2) concentrations in ARE-fed calves were higher than in controls. Serum tumor necrosis factor (TNF-α) concentration was higher in ARE50 and ARE80 groups than ARE0 calves and serum interleukin-6 (IL-6) concentration was higher in ARE80 than in ARE0 calves. Serum immunoglobulin A (IgA), IgG and immunoglobulin M (IgM) concentrations increased with age in ARE-fed calves. ARE supplementation increased the abundance of fiber degrading bacteria. CONCLUSION: ARE at a dosage of 5% to 8% DMI can be supplemented to early weaned yak calves to improve growth performance, antioxidant capacity and immunity. © 2020 Society of Chemical Industry.


Subject(s)
Animal Feed/analysis , Astragalus Plant/metabolism , Cattle/growth & development , Cattle/immunology , Gastrointestinal Microbiome , Animals , Antioxidants/metabolism , Astragalus Plant/chemistry , Cattle/metabolism , Cattle/microbiology , Diet/veterinary , Dietary Supplements/analysis , Female , Male , Plant Extracts/chemistry , Plant Extracts/metabolism , Plant Roots/chemistry , Plant Roots/metabolism , Rumen/metabolism , Rumen/microbiology
19.
Ecotoxicol Environ Saf ; 202: 110908, 2020 Oct 01.
Article in English | MEDLINE | ID: mdl-32800243

ABSTRACT

Chinese milk vetch is an efficient approach to reduce Cd accumulation in rice, nevertheless, its reduction mechanism is not well understood. In this study, we investigated the rice grain Cd, soil properties and microbial community in a Cd-polluted paddy field amended with milk vetch residue (MV) or without (CK) during rice growth period. We found that milk vetch residue averagely decreased the Cd content in rice grain by 45%. Decrease of Cd in rice mainly attributed to the inhibition of Cd activation by milk vetch residue at heading stage probably by the formation of HA-Cd (Humic Acid) and CdS. Increased pH and organic matter (OM) promoted the reduction of available Cd. In addition, nonmetric multidimensional scaling (NMDS) analysis revealed that microbial community structure was significantly different between MV and CK treatment (r = 0.187, p = 0.002), and the core functions of differentially abundant genera were mainly associated with N-cycling, organic matter degradation and sulfate-reducing. The application of milk vetch residue increased the abundance of sulfate-reducing bacteria (SRB) by 8-112% during the rice growth period, which may involve in promoting the transformation of Cd to a more stably residual Cd (CdS). Canonical correspondence analysis (CCA) and mantel test analysis indicated that available K (p = 0.004) and available N (p = 0.005) were the key environmental factors of shaping the SRB. Altogether, changes in soil properties affected microbial structure and functional characteristics, especially the response of SRB in MV treatment would provide valuable insights into reducing the bioavailability of Cd in soil.


Subject(s)
Astragalus Plant/metabolism , Cadmium/metabolism , Oryza/metabolism , Soil Pollutants/metabolism , Animals , Astragalus Plant/microbiology , Biological Availability , Edible Grain/chemistry , Humic Substances/analysis , Industrial Waste , Microbiota , Milk , Soil/chemistry , Soil Pollutants/analysis
20.
J Int Med Res ; 48(5): 300060520903612, 2020 May.
Article in English | MEDLINE | ID: mdl-32475187

ABSTRACT

OBJECTIVES: The objective was to observe the effects of Astragalus polysaccharides on diabetes and on regulation of the TGF-ß/Smad signaling pathway. METHODS: A type 2 diabetic rat model was established with a high-fat diet in combination with low-dose streptozotocin (35 mg/kg). Astragalus polysaccharides were applied as treatment intervention and changes in blood glucose and kidney morphology and function were assessed. RESULTS: Eight weeks after model establishment, kidney weight as a proportion of total weight (KW/TW) in the high-, medium-, and low-dose Astragalus polysaccharide groups was significantly lower than that in the model group, and the KW/TW value gradually decreased with increasing dose of polysaccharides in each treatment group. Fasting blood glucose in the low- and medium-dose Astragalus polysaccharide groups was numerically lower than that in the model group and fasting blood glucose in rats in the high-dose group was significantly lower than that in the model group. Levels of 24-hour urinary microalbumin, creatinine, blood urea nitrogen, collagens I, III, and IV, α-smooth muscle actin, transforming growth factor-ß1, and Smad3 in Astragalus polysaccharide groups (all doses) were significantly lower than those in the model group. CONCLUSIONS: Astragalus polysaccharide significantly improved blood glucose and protected kidney function in a rat diabetes model.


Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Kidney/drug effects , Plant Extracts/pharmacology , Animals , Astragalus Plant/metabolism , Blood Glucose/metabolism , Creatinine/blood , Diabetic Nephropathies/blood , Diet, High-Fat , Disease Models, Animal , Kidney/metabolism , Male , Polysaccharides/pharmacology , Rats , Rats, Sprague-Dawley , Retrospective Studies , Signal Transduction/drug effects , Smad Proteins, Receptor-Regulated/metabolism , Streptozocin/metabolism , Streptozocin/pharmacology , Transforming Growth Factor beta1/metabolism
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