Astragalus membranaceus Polysaccharide Regulates Small Intestinal Microbes and Activates IL-22 Signal Pathway to Promote Intestinal Stem Cell Regeneration in Aging Mice.

Aging can cause degenerative changes in multiple tissues and organs. Gastrointestinal diseases and dysfunctions are common in the elderly population. In this study, we investigated the effects of Astragalus membranaceus polysaccharide (APS) and Astragalus membranaceus ethanol extract (AEE) on age-related intestinal dysfunction and gut microbiota dysbiosis in naturally aging mice. The energy expenditure and physical activity of 23-month-old C57BL6/J mice were recorded using a metabolic cage system. Pathological changes in the intestine were evaluated using Alcian blue staining. The protein levels of leucine-rich repeats containing G protein-coupled receptor 5 (Lgr5) and Stat3 in the small intestine were determined using immunohistochemistry. The intestinal cell migration distance was assessed using bromodeoxyuridine (BrdU) immunofluorescence staining. The gene transcription levels of intestinal stem cell (ISC) markers and ISC-related signaling pathways were detected using quantitative real-time PCR (qRT-PCR). Microbiota analysis based on 16S rDNA was performed to evaluate the composition of the gut microbiota. APS and AEE improved a series of aging phenotypes in female but not in male aging mice. APS and AEE ameliorate intestinal dysfunction and histopathological changes in aging mice. APS had a more significant anti-aging effect than AEE, particularly on intestinal dysfunction. APS promotes ISC regeneration by activating the IL-22 signaling pathway. Cohousing (CH) experiments further confirmed that APS induced the IL-22 signaling pathway by increasing the abundance of Lactobacillus, thereby promoting the regeneration of ISCs. Our results show that APS may serve as a promising agent for improving age-related intestinal dysfunction.

Astragalus root increases Treg and Th17 involvement in embryo implantation and pregnancy maintenance by decreasing CTLA-4+ Tregs.

Maintenance of pregnancy is highly dependent on the maternal immune system. High levels of regulatory T cells (Tregs) accumulate in the maternal placenta to suppress immunoreactivity against fetal antigens. We assessed whether Astragalus root (AsR) and AsR-containing Kampo medicines modulate immunoreactivity and thereby increase mouse litter size. AsR-exposed murine splenocytes exhibited significantly increased IL-2 secretion. In AsR-exposed mice, total Tregs were significantly increased, whereas cytotoxic T lymphocyte antigen 4 (CTLA-4)-positive Tregs were decreased in AsR-exposed mice. Tregs express IL-2 receptor subunit alpha and are activated by IL-2. CTLA-4 interacts with B7 expressed in antigen-presenting cells (APCs) with high affinity, and CTLA-4/B7 signaling plays a critical role in inhibiting APC activity, thereby suppressing CD4+ T cell proliferation and activation. The decrease in CTLA-4+ Tregs in AsR-exposed mice is thought to induce an increase in CD4+ T cells, leading to increased IL-2 secretion from CD4+ T cells followed by Treg activation. Th17 cells prevent trophoblast apoptosis, resulting in trophoblast invasion into the decidua. AsR increases Th17 cells, thereby inducing dose-dependent increases in litter size. Although Keishikaogito (KO)- and Ogikenchuto (OK)-exposed mice exhibited increased IL-2 secretion and splenic Tregs, KO also increased CTLA-4+ Tregs. Therefore, KO promoted immunosuppression by increasing CTLA-4+ Tregs, which induced a decrease in Th17 and exerted little effect on litter size. Therefore, an increase in both Tregs and Th17 cells can be considered necessary for embryo implantation and pregnancy maintenance.

Astraoleanosides E-P, oleanane-type triterpenoid saponins from the aerial parts of Astragalus membranaceus Bunge and their ß-glucuronidase inhibitory activity.

Historically, Astragalus membranaceus Bunge has been used as a beneficial medicinal plant, particularly in the Asian traditional medical systems, for the treatment of various human diseases such as stomach ulcers, diarrhea, and respiratory issues associated with phlegm. In this study, a phytochemical characterization of the aerial parts of A. membranaceusled to the isolation of 29 oleanane-type triterpenoid saponins, including 11 new compounds named astraoleanosides E-P (6-9, 13, 14, 18-22), as well as 18 known ones. The structures of these compounds were elucidated using nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry. Among them, astraoleanoside H (9) and cloversaponin III (15) demonstrated the most potent ß-glucuronidase inhibitory activities, with IC50 values of 21.20 ± 0.75 and 9.05 ± 0.47 µM, respectively, compared to the positive control d-saccharic acid 1,4-lactone (IC50 = 20.62 ± 1.61 µM). Enzyme kinetics studies were then conducted to investigate the type of inhibition exhibited by these active compounds. In addition, the binding mechanism, key interactions, binding stability, and dynamic behavior of protein-ligand complexes were investigated through in silico approaches, such as molecular docking and molecular dynamics simulations. These findings highlight the promising potential of triterpenoid saponins from A. membranaceus as lead compounds for ß-glucuronidase inhibitors, offering new possibilities for the development of therapeutic agents targeting various diseases where ß-glucuronidase plays a crucial role.

Ononin promotes radiosensitivity in lung cancer by inhibiting HIF-1α/VEGF pathway.

BACKGROUND: In our previous study, we provided evidence that Astragalus mongholicus Bunge(AM) and its extracts possess a protective capability against radiation-induced damage, potentially mediated through the reduction of reactive oxygen species (ROS) and nitric oxide (NO). However, we were pleasantly surprised to discover during our experimentation that AM not only offers protection against radiation damage but also exhibits a radiation sensitization effect. This effect may be attributed to a specific small molecule present in AM known as ononin. Currently, radiation sensitizers are predominantly found in nitrazole drugs and nanomaterials, with no existing reports on the radiation sensitization properties of ononin, nor its underlying mechanism. PURPOSE: This study aims to investigate the sensitization effect of the small molecule ononin derived from AM on lung cancer radiotherapy, elucidating its specific molecular mechanism of action. Additionally, the safety profile of combining astragalus small molecule ononin with radiation therapy will be evaluated. METHODS: The effective concentration of ononin was determined through cell survival experiments, and the impact of ononin combined with varying doses of radiation on lung cancer cells was observed using CCK-8 and cell cloning experiments. The apoptotic effect of ononin combined with radiation on lung cancer cells was assessed using Hochester staining, flow cytometry, and WB assay. Additionally, WB and immunofluorescence analysis were conducted to investigate the influence of ononin on HIF-1α/VEGF pathway. Furthermore, Molecular Dynamics Simulation was employed to validate the targeted binding ability of ononin and HIF-1α. A lung cancer cell line was established to investigate the effects of knockdown and overexpression of HIF-1α. Subsequently, the experiment was repeated using tumor bearing nude mice and C57BL/6 mouse models in an in vivo study. Tumor volume was measured using a vernier caliper, while HE, immunohistochemistry, and immunofluorescence techniques were employed to observe the effects of ononin combined with radiation on tumor morphology, proliferation, and apoptosis. Additionally, Immunofluorescence was employed to examine the impact of ononin on HIF-1α/VEGF pathway in vivo, and its effect on liver function in mice was assessed through biochemistry analysis. RESULTS: At a concentration of 25 µM, ononin did not affect the proliferation of lung epithelial cells but inhibited the survival of lung cancer cells. In vitro experiments demonstrated that the combination of ononin and radiation could effectively inhibit the growth of lung cancer cells, induce apoptosis, and suppress the excessive activation of the Hypoxia inducible factor 1 alpha/Vascular endothelial growth factor pathway. In vivo experiments showed that the combination of ononin and radiation reduced the size and proliferation of lung cancer tumors, promoted cancer cell apoptosis, mitigated abnormal activation of the Hypoxia inducible factor 1 alpha pathway, and protected against liver function damage. CONCLUSION: This study provides evidence that the combination of AM and its small molecule ononin can enhance the sensitivity of lung cancer to radiation. Additionally, it has been observed that this combination can specifically target HIF-1α and exert its effects. Notably, ononin exhibits the unique ability to protect liver function from damage while simultaneously enhancing the tumor-killing effects of radiation, thereby demonstrating a synergistic and detoxifying role in tumor radiotherapy. These findings contribute to the establishment of a solid basis for the development of novel radiation sensitizers derived from traditional Chinese medicine.

Systematic Pharmacology and Experimental Validation to Reveal the Alleviation of Astragalus membranaceus Regulating Ferroptosis in Osteoarthritis.

Background: Astragalus membranaceus (AM) shows promise as a therapeutic agent for osteoarthritis (OA), a debilitating condition with high disability rates. OA exacerbation is linked to chondrocyte ferroptosis, yet the precise pharmacological mechanisms of AM remain unclear. Methods: We validated AM's protective efficacy in an anterior cruciate ligament transection (ACLT) mouse model of OA. The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database was utilized to identify AM's active components and their targets. FerrDb (a database for regulators and markers of ferroptosis and ferroptosis-disease associations) pinpointed ferroptosis-related targets, while GeneCards, Online Mendelian Inheritance in Man (OMIM), Pharmacogenomics Knowledgebase (PharmGKB), Therapeutic Target Database (TTD), and DrugBank sourced OA-related genes. Molecular docking analysis further validated these targets. Ultimately, the validation of the results was accomplished through in vitro experiments. Results: AM exhibited anabolic effects and suppressed catabolism in OA chondrocytes. Network pharmacology identified 19 common genes, and molecular docking suggested quercetin, an AM constituent, interacts with key proteins like HO-1 and NRF2 to inhibit chondrocyte ferroptosis. In vitro experiments confirmed AM's ability to modulate the NRF2/HO-1 pathway via quercetin, mitigating chondrocyte ferroptosis. Conclusion: This study elucidates how AM regulates chondrocyte ferroptosis, impacting OA progression, providing a theoretical basis and experimental support for AM's scientific application.

The effect of different LED wavelengths on the components and biosynthesis of isoflavonoid in sprout Astragalus membranaceus.

An artificial light source is the optimal element for studying the usability of the medicinal plant Astragalus membranaceus as a sprout vegetable. Based on artificial light source conditions, formononetin (FO) level was the highest (2.6 mg/L) in A. membranaceus exposed to white light emitting diode (LED) light, and calycosin (CA) level was the highest (3.09 mg/L) in the plant exposed to red LED light. According to the publicly available transcriptome data of LED-exposed sprout A. membranaceus LED, reference genes related to the content enhancement of FO, an isoflavone compound, and those related to the content enhancement of CA were selected. The expression patterns of these genes were assayed using qPCR. Among the genes related to FO enhancement, Gene-225190T showed the highest mRNA levels in cells of LED-white light-exposed sprout A. membranaceus; among the genes related to CA enhancement, Gene_042770T showed the highest expression under red LED light. Most genes related to the overall biosynthesis regulation of flavonoids of the upper concept of isoflavone were highly expressed in response to red LED light, and the transcriptional level of 4CL in response to red LED light was the highest. Based on these results, the artificial light sources that regulated the FO and CA contents in sprouts A. membranaceus were white and red LED lights, and the selected reference genes were capable of regulating isoflavone biosynthesis.

Effects of dietary Astragalus membranaceus and Codonopsis pilosula extracts on growth performance, antioxidant capacity, immune status, and intestinal health in broilers.

The objective of this study was to examine the effects of dietary Chinese herbal medicine (CHM) consisting of Astragalus membranaceus (Fisch.) Bunge (AMT) and Codonopsis pilosula (Franch.) Nannf (CPO) extracts on growth performance, antioxidant capacity, immune status, and intestinal health of broiler chickens. Two groups were formed, each consisting of six replicates of 12 one-day-old healthy male 817 white feather broilers. Broilers were fed either a basal diet (CON group) or a basal diet supplemented with 500 mg/kg CHM. The trial lasted 50 days. The results showed that CHM supplementation resulted in enhanced feed efficiency and antioxidant capacity in both the serum and liver, while it reduced uric acid and endotoxin levels, as well as diamine oxidase activity (p < 0.05). Additionally, CHM treatment increased the height of jejunum villi and upregulated Claudin-1 expression in the jejunal mucosa accompanied by an increase in the mRNA levels of interleukin-6 (IL-6), interferon-γ (IFN-γ), interferon-ß (IFN-ß), tumor necrosis factor-α (TNF-α), and anti-inflammatory cytokine interleukin-10 (IL-10) (p < 0.05). The presence of dietary CHM caused an increase in the proportions of Bacteroidetes and unclassified Bacteroidales but led to a decrease in those of Firmicutes and Alistipes (p < 0.05). The composition of the jejunal mucosa microbiota was correlated with the feed conversion ratio, serum metabolites, and gene expression based on Spearman correlation analysis. The findings indicated that the consumption of dietary CHM improved the utilization of feed, increased the mRNA expression of pro-inflammatory cytokines in the jejunal mucosa, and decreased the endotoxin level and activities of diamine oxidase and lactate dehydrogenase in the serum, which could potentially be linked to changes in the gut microbiota of broiler chickens.

Qilian Formula Inhibits Tumor Cell Growth in a Bone Metastasis Model of Lung Cancer.

BACKGROUND: Bone metastasis is frequently common in advanced lung cancer with the major issue of a pathological fracture. Previous studies suggested that Astragalus membranaceus (Qi) and Ampelopsis japonica (Lian), which are used as folk medicine in China, have potential effects on inhibiting tumor growth and protecting bones, respectively. In this study, an experiment on the inhibitory effect of the Qilian formula (AAF) in vivo was designed to examine tumor growth in bone and osteoclast formation. MATERIALS AND METHODS: The bone metastasis xenograft models were established by implanting NCI-H460-luc2 lung cancer cells into the right tibiae bones of mice. After confirming the model's viability through optical imaging 7 days post-implantation, 2 groups, namely the AAF group and the control group, were administered 0.3 mL of AAF extract (9 g/kg/day) or normal saline via intragastric delivery for a duration of 4 weeks. Throughout the study, we longitudinally assessed tumor burden, bone destruction, and weight-bearing capacity in vivo using reporter gene bioluminescence imaging (BLI), micro-CT, and dynamic weight-bearing (DWB) tests. Mechanistic insights were gained through Hematoxylin-eosin (H&E) staining, immunohistochemical (IHC) analysis, western blotting, and flow cytometry. RESULTS: Qilian formula produced significant inhibition to the progress of bone destruction and tumor burden in the right tibiae bone in the treatment group. It was further evidenced by molecular imaging in vivo via small animal micro-CT and BLI with parametric quantification, characterizing significantly lower uptake of BLI signal in the treated tumor lesions and improving the pathological changes in the microstructure of bone. Furthermore, DWB tests revealed that Qilian formula treatment significantly maintained the weight-bearing capacity. According to immunohistochemical analysis, the effect of the Qilian formula appeared to involve the suppression of osteoclast formation by lower expression of the tartrate-resistant acid phosphatase. Cell apoptosis and death induction were evidenced by a higher percentage of Bal2、BAX and caspase 3 expressions of Qilian formula-treated tumor tissues. CONCLUSIONS: Our study demonstrated a significant inhibitory effect of the Qilian formula on the progression of osteolytic invasion in vivo by suppressing osteoclastogenesis and promoting apoptotic cell death.

Astragalus membranaceus and Cinnamomum cassia Stimulate the Hair Follicle Differentiation-Related Growth Factor by the Wnt/ß-Catenin Signaling Pathway.

Astragalus membranaceus and Cinnamomum cassia are used as spices and flavorful ingredients, or medicinal herbs with pharmacological effects. In this study, the hair-growth-promoting effects of the YH complex, a newly developed formula consisting of membranaceus and C. cassia, are investigated with the prediction of its molecular mechanism. The target gene of the YH complex was about 74.8% overlapped with the gene set of 'Hair growth' on the GO Biological Process database. The oral administration of the YH complex promoted hair regrowth and increased hair-shaft thickness in depilated hair loss mice. In addition, the anagen/telogen hair follicle ratio was significantly increased by the YH complex. The growth factors affecting the growth of hair follicles were dose-dependently increased by treatment with the YH complex. The Wnt/ß-catenin signaling pathway expressions in skin tissues were apparently increased by the administration of the YH complex. In conclusion, the YH complex consisting of A. membranaceus and C. cassia induced hair follicle differentiation and preserved the growing-anagen phase by increasing growth factors and the Wnt/ß-catenin signaling pathway, leading to the restoration of hair loss. The YH complex can be a remedy for hair loss diseases, such as alopecia areata, androgenetic alopecia, telogen effluvium, and chemotherapy-induced alopecia.

A Network Pharmacology Prediction and Molecular Docking-Based Strategy to Explore the Potential Pharmacological Mechanism of Astragalus membranaceus for Glioma.

Glioma treatment in traditional Chinese medicine has a lengthy history. Astragalus membranaceus, a traditional Chinese herb that is frequently utilized in therapeutic practice, is a component of many Traditional Chinese Medicine formulas that have been documented to have anti-glioma properties. Uncertainty persists regarding the molecular mechanism behind the therapeutic effects. Based on results from network pharmacology and molecular docking, we thoroughly identified the molecular pathways of Astragalus membranaceus' anti-glioma activities in this study. According to the findings of the enrichment analysis, 14 active compounds and 343 targets were eliminated from the screening process. These targets were mainly found in the pathways in cancer, neuroactive ligand-receptor interaction, protein phosphorylation, inflammatory response, positive regulation of phosphorylation, and inflammatory mediator regulation of Transient Receptor Potential (TRP) channels. The results of molecular docking showed that the active substances isoflavanone and 1,7-Dihydroxy-3,9-dimethoxy pterocarpene have strong binding affinities for the respective targets ESR2 and PTGS2. In accordance with the findings of our investigation, Astragalus membranaceus active compounds exhibit a multicomponent and multitarget synergistic therapeutic impact on glioma by actively targeting several targets in various pathways. Additionally, we propose that 1,7-Dihydroxy-3,9-dimethoxy pterocarpene and isoflavanone may be the main active ingredients in the therapy of glioma.

The Effect of Astragalus on Humoral and Cellular Immune Response: A Systematic Review and Meta-Analysis of Human Studies.

INTRODUCTION: Astragalus is used in traditional Chinese medicine for immune system disorders. Its effect on immune system function is evaluated in multiple studies. The objective of this systematic review and meta-analysis was to evaluate the effect of Astragalus on humoral and cellular immune response in human studies. METHODS: A comprehensive search of electronic databases was conducted to identify relevant studies published up to April 2023. Studies that assessed the impact of Astragalus on humoral and cellular immune markers were included. The data were extracted, and a random-effects meta-analysis was performed to determine the overall effect size. Subgroup analyses were conducted based on outcome measures. RESULTS: A total of 19 studies, including 1,094 human participants, were included in the meta-analysis. The analysis of humoral immune markers revealed a significant reduction in proinflammatory cytokines, including IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ, following Astragalus intervention (SMD -2.8765, 95% CI: -3.2385 to -2.5145, p < 0.0001). In the cellular immunity domain, Astragalus was found to significantly increase CD3 levels and the CD4/CD8 ratio (SMD 2.4629, 95% CI: 1.9598; 2.9661). Subgroup analyses based on outcome measures supported these findings. However, substantial heterogeneity was observed among the included studies. CONCLUSION: This systematic review and meta-analysis provide evidence supporting the immunomodulatory effects of Astragalus on humoral and cellular response. Astragalus demonstrated a significant reduction in proinflammatory cytokines and an enhancement of cellular immune markers, suggesting its potential as a therapeutic agent for immune-related disorders.Astragalus wird in der traditionellen chinesischen Medizin bei Erkrankungen des Immunsystems eingesetzt. Seine Wirkung auf das Immunsystem ist in mehreren Studien untersucht worden. Das Ziel dieser systematischen Übersichtsarbeit und Metaanalyse ist es, die Wirkung von Astragalus auf die humorale und zelluläre Immunantwort in Studien am Menschen zu untersuchen.Eine umfassende Suche in elektronischen Datenbanken wurde durchgeführt, um einschlägige Studien zu finden, die bis April 2023 veröffentlicht wurden. Eingeschlossen wurden Studien, die die Auswirkung von Astragalus auf Marker der humoralen und zellulären Immunantwort untersuchten. Die Daten wurden extrahiert und eine Random-Effects-Metaanalyse durchgeführt, um die Gesamt-Effektstärke zu ermitteln. Subgruppenanalysen wurden basierend auf Zielgrößen durchgeführt.Insgesamt 19 Studien mit 1'094 menschlichen Teilnehmern wurden in die Metaanalyse eingeschlossen. Die Analyse der humoralen Immunmarker ergab eine signifikante Abnahme proinflammatorischer Zytokine, darunter IL-2, IL-4, IL-6, IL-10, TNF-α und IFN-γ, nach Anwendung von Astragalus (SMD ­2.8765; 95%-KI: −3.2385, −2.5145; p < 0.0001). Bei der zellulären Immunität zeigte Astralagus eine signifikante Erhöhung der CD3-Konzentration und des CD4/CD8-Quotienten (SMD 2.4629; 95%-KI: 1.9598, 2.9661). Die Subgruppenanalysen nach Zielgrößen bestätigten diese Ergebnisse. Zwischen den eingeschlossenen Studien bestand jedoch erhebliche Heterogenität.Diese systematische Übersichtsarbeit und Metaanalyse liefert Belege für die immunmodulatorischen Effekte von Astragalus auf die humorale und zelluläre Immunantwort. Astragalus zeigte eine signifikante Abnahme proinflammatorischer Zytokine und eine Verbesserung von Markern der zellulären Immunität, was auf sein Potenzial als Therapeutikum bei immunvermittelten Störungen hindeutet.

Insights into the Mechanism of Supramolecular Self-Assembly in the Astragalus membranaceus-Angelica sinensis Codecoction.

Astragalus membranaceus (Fisch.) Bge. (AM) and Angelica sinensis (Oliv.) Diels (AS) constitute a classic herb pair in prescriptions to treat myocardial fibrosis. To date, research on the AM-AS herb pair has mainly focused on the chemical compositions associated with therapeutic efficacy. However, supermolecules actually exist in herb codecoctions, and their self-assembly mechanism remains unclear. In this study, supermolecules originating from AM-AS codoping reactions (AA-NPs) were first reported. The chemical compositions of AA-NPs showed a dynamic self-assembly process. AA-NPs with different decoction times had similar surface groups and amorphous states; however, the size distributions of these nanoparticles might be different. Taking the interaction between Z-ligustilide and astragaloside IV as an example to understand the self-assembly mechanism of AA-NPs, it was found that the complex could be formed with a molar ratio of 2:1. Later, AA-NPs were proven to be effective in the treatment of myocardial fibrosis both in vivo and in vitro, the in-depth mechanisms of which were related to the recovery of cardiac function, reduced collagen deposition, and inhibition of the endothelial-to-mesenchymal transition that occurred in the process of myocardial fibrosis. Thus, AA-NPs may be the chemical material basis of the molecular mechanism of the AM-AS decoction in treating isoproterenol-induced myocardial fibrosis. Taken together, this work provides a supramolecular strategy for revealing the interaction between effective chemical components in herb-pair decoctions.

Astragalus membranaceus and Salvia miltiorrhiza ameliorate diabetic kidney disease via the "gut-kidney axis".

BACKGROUND: The combination of Astragalus membranaceus and Salvia miltiorrhiza (AS) is an effective prescription for treating diabetic kidney disease (DKD) in traditional Chinese medicine. Its efficacy in treating DKD has been confirmed, but the potential regulatory mechanism has not yet been fully clarified. PURPOSE: To explore the mechanism by which AS regulates the "gut-metabolism-transcription" coexpression network under the action of the "gut-kidney axis" to ameliorate DKD. METHODS: SD rats were used to establish the DKD model by injecting STZ. After AS intervention, the structure and function of the kidney and colon were observed. We sequenced the gut microbiota utilizing 16S rDNA, identified serum differential metabolites using LC‒MS/MS, and observed renal mRNA expression by RNA seq. The "gut-metabolism-transcription" coexpression network was further constructed, and the target bacteria, target metabolites, and target genes of AS were ultimately screened and validated. RESULTS: AS improved renal pathology and functional damage and increased the abundance of Akkermansia, Akkermansia_muciniphila, Lactobacillus and Lactobacillus_murinus. Fourteen target metabolites of AS were identified, which were mainly concentrated in 19 KEGG pathways, including sphingolipid metabolism and glycerophospholipid metabolism. Sixty-three target mRNAs of AS were identified. The top 20 pathways were closely related to glycolipid metabolism, and 14 differential mRNAs were expressed in these pathways. Correlation analysis showed that Akkermansia, Akkermansia muciniphila, Lactobacillus and Lactobacillus murinus were closely associated with sphingolipid metabolism, glycerophospholipid metabolism, arachidonic acid metabolism, ascorbate and aldarate metabolism and galactose metabolism. Moreover, the target metabolites and target mRNAs of AS were also enriched in five identical pathways of sphingolipid metabolism, glycerophospholipid metabolism, arachidonic acid metabolism, ascorbate and aldarate metabolism and galactose metabolism, including 8 different metabolites, such as sphingosine, and 5 different genes, such as Kng1. The 8 metabolites had high AUC prediction values, and the validation of the 5 genes was consistent with the sequencing results. CONCLUSION: Our research showed that AS can improve DKD via the "gut-kidney axis". Akkermansia muciniphila and Lactobacillus murinus were the main driving bacteria, and five pathways related to glycolipid metabolism, especially sphingolipid metabolism and glycerophospholipid metabolism, may be important follow-up reactions and regulatory mechanisms.

Fermented Astragalus membranaceus could promote the liver and intestinal health of juvenile tiger grouper (Epinephelus fuscoguttatus).

In order to understand the effects of fermented Astragalus membranaceus (FAM) on the liver and intestinal health of tiger grouper (Epinephelus fuscoguttatus), this study was conducted. This study evaluates the effects of different levels of FAM on liver and intestinal tissue structure, serum biochemical parameters, intestinal digestive enzyme, and microbiota structure of tiger grouper. Fish were fed with diets (crude protein ≥ 48.0%, crude fat ≥ 10.0%) with five levels of FAM (L1:0.25%, L2: 0.5%, L3: 1%, L4: 2% and L5: 4%) in the experimental groups and a regular diet was used as the control (L0: 0%) for 8 weeks. Compared with AM, the protein content of FAM was significantly changed by 34.70%, indicating that a large amount of bacterial protein was produced after AM fermentation, and its nutritional value was improved. FAM had significant effects on the growth performance of tiger grouper (p < 0.05). The high-density lipoprotein cholesterol (HDL-C) was highest in L4 group, being significantly different from L0 group. The area and diameter of hepatocytes were lowest in L3 and L4, and the density of hepatocyte was highest in L4 group and relatively decreased in L5 group. The mucosal height and muscular thickness were highest in L3 group. The intestinal microbiota structure of tiger grouper was changed under the intervention of FAM. The lower abundance of potential pathogenic bacteria and higher abundance of probiotics colonization in the L4 group showed that the dose of FAM had the best effect on improving the health of intestinal microbiota. This study indicates that the addition of FAM in the feed contributes to liver health, improves intestinal morphology, and regulates the intestinal microbiota of tiger grouper. The addition ratio of 1%-2% is better for intestinal and liver health, and a high addition ratio will cause liver damage. Our work will provide a reference for the addition and management of FAM in the aquaculture industry.

Simultaneous determination and pharmacokinetics study of three triterpenoid saponins in rat plasma by ultra-high-performance liquid chromatography tandem mass-spectrometry after oral administration of Astragalus Membranaceus leaf extract.

A selective and sensitive ultra-high-performance liquid chromatography-tandem mass spectrometry method was developed and validated for the determination of three triterpenoid saponins isolated from Astragalus membranaceus leaf extract. In this article, a method for simultaneous determination of Huangqiyenin A, Huangqiyenin E, and Huangqiyenin K was established for the first time. The method was successfully applied to the pharmacokinetic study of Astragalus membranaceus leaf extract after oral administration. Liquid-liquid extraction was applied to plasma sample preparation. Multiple reaction monitoring mode with an electrospray ion source in positive electrospray ionization was chosen to quantify the analytes. Chromatographic separation was performed on a Waters HSS T3 column, using gradient elution with a mobile phase composed of acetonitrile and 5 mM ammonium acetate/water. The pharmacokinetic results showed that all three compounds had the characteristics of rapid absorption-slow metabolism trend. The time of maximum plasma concentration of Huangqiyenin A is higher than Huangqiyenin E and Huangqiyenin K. And the maximum plasma concentration of Huangqiyenin A is higher as well. The pharmacokinetic results revealed the pharmacokinetic characteristics of the three analytes in rat plasma, which could provide a helpful reference for the further study of Astragalus membranaceus leaf extract.

Astragalus membranaceus as a Drug Candidate for Inflammatory Bowel Disease: The Preclinical Evidence.

Inflammatory bowel disease (IBD) is a group of chronic inflammatory disorders that include Crohn's disease (CD) and ulcerative colitis (UC). Today, IBD has no successful treatment. As a result, it is of paramount importance to develop novel therapeutic agents for IBD prevention and treatment. Astragalus membranaceus (AMS) is a traditional Chinese medicine found in the AMS root. Modern pharmacological studies indicate that AMS and its constituents exhibit multiple bioactivities, such as anti-inflammatory, anti-oxidant, immune regulatory, anticancer, hypolipidemic, hypoglycemic, hepatoprotective, expectorant, and diuretic effects. AMS and its active constituents, which have been reported to be effective in IBD treatment, are believed to be viable candidate drugs for IBD treatment. These underlying mechanisms are associated with anti-inflammation, anti-oxidation, immunomodulation, intestinal epithelial repair, gut microbiota homeostasis, and improved energy metabolism. In this review, we summarize the efficacy and underlying mechanisms involved in IBD treatment with AMS and its active constituents in preclinical studies.

Dietary supplementation with different alternative to in-feed antibiotic improves growth performance of broilers during specific phases.

The effects of substituting Bacillus subtilis, Astragalus membranaceus, and enzymes for aureomycin to improve the growth performance of broilers during specific phases were studied to develop alternatives to in-feed antibiotics and decrease drug residues in meat food and antibiotic resistance. Six hundred one-day-old broilers were randomly assigned to 5 groups. Broilers in the control group were supplied with basal diets (CT), and those in the remaining 4 groups were supplied with feed containing aureomycin premix (AU), B. subtilis powder (BS), A. membranaceus root powder (AM), and enzyme compound powder (EN), respectively. Compared to the control group, broilers in the other groups exhibited better growth performance during different phases. Microbial analysis of cecal contents suggested that treatment with BS or EN significantly increased the abundance of Lactobacillus or Bifidobacteria but inhibited Escherichia coli or Clostridium welchii; however, these bacteria were suppressed by AU treatment except C. welchii. The digestibility of the feed in vitro was significantly enhanced by adding BS or EN to the feed, consistent with findings for growth performance. In conclusion, dietary supplementation with 3 additives could improve the growth performance of broilers during specific phases. Future studies should focus on designing suitable schedules to partially replace in-feed antibiotics.

Density-oriented deep eutectic solvent-based system for the selective separation of polysaccharides from Astragalus membranaceus var. Mongholicus under ultrasound-assisted conditions.

The water extraction and ethanol precipitation method is an extraction method based on the solubility characteristics of polysaccharides that offers wide applicability in the extraction and separation of plant polysaccharides. However, this method leads to large amounts of proteins, nucleic acids, pigments, and other impurities in the polysaccharides products, which makes downstream purification complicated and time-consuming. In this study, a green, high-density natural deep eutectic solvents was used for the high-purity extraction and separation of polysaccharides from Astragalus membranaceus (Fisch) Bge. var. Mongholicus (Bge.) Hsiao roots under ultrasound-assisted conditions. In this study, 16 different natural deep eutectic solvents were designed to screen the best solvent for extracting Astragalus polysaccharides (APSs). Based on the yield and recovery of APSs, a natural deep eutectic solvents composed of choline chloride and oxalic acid with a molar ratio of 1:2 was selected. The related factors affecting polysaccharides extraction and solvent precipitation were investigated. To improve the operating methodology, single-factor trials, a Plackett-Burman design, and a Box-Behnken design were used. The optimal extraction process conditions were obtained as follows: water content of 55%, liquid-solid ratio of 24 mL/g, ultrasonic irradiation time of 54 min, ultrasonic irradiation temperature of 50 °C, ultrasonic irradiation power of 480 W, ethanol precipitation time of 24 h, and ethanol concentration of 75%. Under optimal extraction conditions, the recovery of APSs was 61.4 ± 0.6 mg/g. Considering the special matrix characteristics of A. membranaceus var. Mongholicus roots, physical-technology-based ultrasonic waves promote penetration, and the mass transfer function also solves the bottleneck of high-viscosity deep eutectic solvents in the extraction stage. In comparison with the conventional method, the proposed method based on deep eutectic solvents isolation can significantly increase APSs recovery, which is beneficial to simplifying the process of polysaccharides purification by using solvent properties to separate extracts and reduce impurities in APSs.

The use of Astragalus membranaceus as an eco-friendly alternative for antibiotics in diets of Japanese quail breeders.

Mature Japanese quails (n. 180), aged 8 wk, were divided into 6 groups to evaluate the influence of dietary Astragalus membranaceus powder on laying and reproductive performances, quality of egg, and blood metabolites. A completely randomized design experiment was performed including 6 groups. The first group of quails was served as control (basal diet). While, the 2nd, 3rd, 4th, 5th, and 6th group of quails fed a basal diet supplemented with 1, 2, 3, 4, and 5 g of AM powder/kg diet, respectively. Egg number (EN), weight (EW), and mass (EM) were not significantly influenced by dietary Astragalus membranaceus at all tested levels. The hatchability percentage was quadratically improved by dietary supplementation of A. membranaceus. Dietary supplementation of A. membranaceus positively affects (linear and quadratic) liver and kidney functions. Plasma total cholesterol (TC; P < 0.001) and Triglyceride (TG; P < 0.001) were linearly and quadratically decreased by dietary A. membranaceus increasing level. Blood urea level decreased with increasing A. membranaceus levels in the quail diet. The immunoglobulin G (IgG) and M (IgM) were higher than the control at all A. membranaceus levels. In conclusion, feeding quail breeders with Astragalus membranaceus at 1 g/kg diet has beneficial effects on feed conversion ratio; on production at 2 g/kg diet; on hatchability and immunity at 5 g/kg diet; and on total cholesterol at 3 g/kg diet and on shell quality at 4 g/kg diet. A. membranaceus products are expected to be novel valuable dietary supplements for poultry production, depending on the target trait.

Beneficial Effects of Astragalus membranaceus (Fisch.) Bunge Extract in Controlling Inflammatory Response and Preventing Asthma Features.

Astragalus membranaceus (Fisch.) Bunge root is used as herbal medicine for its immunomodulating activities in Chinese medicine. Recently, beneficial properties of A. membranaceus on allergic diseases have been proposed. Here we investigated the role of a commercial extract of A. membranaceus, standardized to 16% polysaccharides, in regulating the immune-inflammatory response in vitro and in vivo and its therapeutic application in asthma. A. membranaceus extract inhibited prostaglandin E2 and leukotriene C4 production in stimulated J774 and peritoneal macrophages, respectively. The extract also reduced interlukin-1ß, tumor necrosis factor-α, and nitrite production, affecting inducible nitric oxide synthase expression. In vivo experiments confirmed the anti-inflammatory properties of A. membranaceus, as evident by a reduction in zymosan-induced peritoneal cellular infiltration and pro-inflammatory mediator production. The efficacy of A. membranaceus extract in modulating the immune response was confirmed in a model of allergic airway inflammation. Extracts improve lung function by inhibiting airway hyperresponsiveness, airway remodeling, and fibrosis. Its anti-asthmatic effects were further sustained by inhibition of the sensitization process, as indicated by a reduction of ovalbumin-induced IgE levels and the mounting of a Th2 immune response. In conclusion, our data demonstrate the anti-inflammatory properties of the commercial extract of A. membranaceus and its beneficial effects on asthma feature development.