Exploration of the underlying mechanism of Astragaloside III in attenuating immunosuppression via network pharmacology and vitro/vivo pharmacological validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Astragalus mongholicus Bunge (AM, recorded in http://www.worldfloraonline.org, 2023-08-03) is a kind of medicine food homology plant with a long medicinal history in China. Astragaloside III (AS-III) has immunomodulatory effects and is one of the most active components in AM. However, its underlying mechanism of action is still not fully explained. AIM OF THE STUDY: The research was designed to discuss the protective effects of AS-III on immunosuppression and to elucidate its prospective mechanism. MATERIALS AND METHODS: Molecular docking methods and network pharmacology analysis were used to comprehensively investigate potential targets and relative pathways for AS-III and immunosuppression. In order to study and verify the pharmacological activity and mechanism of AS-III in alleviating immunosuppression, immunosuppression mouse model induced by cyclophosphamide (CTX) in vivo and macrophage RAW264.7 cell model induced by hypoxia/lipopolysaccharide (LPS) in vitro were used. RESULTS: A total of 105 common targets were obtained from the AS-III-related and immunosuppression-related target networks. The results of network pharmacology and molecular docking demonstrate that AS-III may treat immunosuppression through by regulating glucose metabolism-related pathways such as regulation of lipolysis in adipocytes, carbohydrate digestion and absorption, cGMP-PKG signaling pathway, central carbon metabolism in cancer together with HIF-1 pathway. The results of molecular docking showed that AS-III has good binding relationship with LDHA, AKT1 and HIF1A. In CTX-induced immunosuppressive mouse model, AS-III had a significant protective effect on the reduction of body weight, immune organ index and hematological indices. It can also protect immune organs from damage. In addition, AS-III could significantly improve the expression of key proteins involved in energy metabolism and serum inflammatory factors. To further validate the animal results, an initial inflammatory/immune response model of macrophage RAW264.7 cells was constructed through hypoxia and LPS. AS-III improved the immune function of macrophages, reduced the release of NO, TNF-α, IL-1ß, PDHK-1, LDH, lactate, HK, PK and GLUT-1, and restored the decrease of ATP caused by hypoxia. Besides, AS-III was also demonstrated that it could inhibit the increase of HIF-1α, PDHK-1 and LDH by adding inhibitors and agonists. CONCLUSIONS: In this study, the main targets of AS-III for immunosuppressive therapy were initially analyzed. AS-III was systematically confirmed to attenuates immunosuppressive state through the HIF-1α/PDHK-1 pathway. These findings offer an experimental foundation for the use of AS-III as a potential candidate for the treatment of immunosuppression.

Mechanism of Astragalus mongholicus Bunge ameliorating cerebral ischemia-reperfusion injury: Based on network pharmacology analysis and experimental verification.

ETHNOPHARMACOLOGICAL RELEVANCE: Astragalus mongholicus Bunge (AMB) is a herb with wide application in traditional Chinese medicine, exerting a wealth of pharmacological effects. AMB has been proven to have an evident therapeutic effect on ischemic cerebrovascular diseases, including cerebral ischemia-reperfusion injury (CIRI). However, the specific mechanism underlying AMB in CIRI remains unclear. AIM OF THE STUDY: This study aimed to investigate the potential role of AMB in CIRI through a comprehensive approach of network pharmacology and in vivo experimental research. METHODS: The intersection genes of drugs and diseases were obtained through analysis of the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and Gene Expression Omnibus (GEO) database. The protein-protein interaction (PPI) network was created through the string website. Meanwhile, the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was carried out using R studio, and thereafter the key genes were screened. Then, the molecular docking prediction was made between the main active ingredients and target genes, and hub genes with high binding energy were obtained. In addition, molecular dynamic (MD) simulation was used to validate the result of molecular docking. Based on the results of network pharmacology, we used animal experiments to verify the predicted hub genes. First, the rat middle cerebral artery occlusion and reperfusion (MACO/R) model was established and the effective dose of AMB in CIRI was determined by behavioral detection and 2,3,5-Triphenyltetrazolium chloride (TTC) staining. Then the target proteins corresponding to the hub genes were measured by Western blot. Moreover, the level of neuronal death was measured using hematoxylin and eosin (HE) and Nissl staining. RESULTS: Based on the analysis of the TCMSP database and GEO database, a total of 62 intersection target genes of diseases and drugs were obtained. The KEGG enrichment analysis showed that the therapeutic effect of AMB on CIRI might be realized through the advanced glycation endproduct-the receptor of advanced glycation endproduct (AGE-RAGE) signaling pathway in diabetic complications, nuclear factor kappa-B (NF-κB) signaling pathway and other pathways. Molecular docking results showed that the active ingredients of AMB had good binding potential with hub genes that included Prkcb, Ikbkb, Gsk3b, Fos and Rela. Animal experiments showed that AWE (60 g/kg) could alleviate CIRI by regulating the phosphorylation of PKCß, IKKß, GSK3ß, c-Fos and NF-κB p65 proteins. CONCLUSION: AMB exerts multi-target and multi-pathway effects against CIRI, and the underlying mechanism may be related to anti-apoptosis, anti-inflammation, anti-oxidative stress and inhibiting calcium overload.

Electronic eye and electronic tongue data fusion combined with a GETNet model for the traceability and detection of Astragalus.

BACKGROUND: Astragalus is a widely used traditional Chinese medicine material that is easily confused due to its quality, price and other factors derived from different origins. This article describes a novel method for the rapid tracing and detection of Astragalus via the joint application of an electronic tongue (ET) and an electronic eye (EE) combined with a lightweight convoluted neural network (CNN)-transformer model. First, ET and EE systems were employed to measure the taste fingerprints and appearance images, respectively, of different Astragalus samples. Three spectral transform methods - the Markov transition field, short-time Fourier transform and recurrence plot - were utilized to convert the ET signals into 2D spectrograms. Then, the obtained ET spectrograms were fused with the EE image to obtain multimodal information. A lightweight hybrid model, termed GETNet, was designed to achieve pattern recognition for the Astragalus fusion information. The proposed model employed an improved transformer module and an improved Ghost bottleneck as its backbone network, complementarily utilizing the benefits of CNN and transformer architectures for local and global feature representation. Furthermore, the Ghost bottleneck was further optimized using a channel attention technique, which boosted the model's feature extraction effectiveness. RESULTS: The experiments indicate that the proposed data fusion strategy based on ET and EE devices has better recognition accuracy than that attained with independent sensing devices. CONCLUSION: The proposed method achieved high precision (99.1%) and recall (99.1%) values, providing a novel approach for rapidly identifying the origin of Astragalus, and it holds great promise for applications involving other types of Chinese herbal medicines. © 2024 Society of Chemical Industry.

Astragalus polysaccharides ameliorates experimental colitis by regulating memory B cells metabolism.

It is well-established that the reduced Memory B cells (MBCs) play an important role in the pathogenesis of ulcerative colitis (UC), rendering them a potential therapeutic target for UC intervention. Astragalus polysaccharide (APS), a primary active constituent derived from the classic traditional Chinese medicine Astragalus membranaceus (AM), has been used for centuries in the treatment of UC in both human and animal subjects due to its renowned immunomodulatory properties. However, it is unknown whether APS can regulate MBCs to alleviate experimental colitis. In the present investigation, the murine colitis was successfully induced using dextran sulphate sodium (DSS) and subsequently treated with APS for a duration of 7 days. APS exhibited significant efficacy in reducing the disease activity index (DAI), colonic weight index, the index of colonic weight/colonic length. Furthermore, APS mitigated colonic pathological injuries, restored the colonic length, elevated the immunoglobulin A (IgA), transforming growth factor-ß1 (TGF-ß1) and interleukin (IL)-10 levels, while concurrently suppressing IgG, IgM, IL-6, tumor necrosis factor alpha (TNF-α) levels. Crucially, the quantities of MBCs, IgA+MBCs and forkhead box P3 (Foxp3+) MBCs were notably increased along with a concurrent decrease in IgG1+MBCs, IG2a+MBCs, IgG2b+MBCs after APS administration in colitis mice. Additionally, the Mitotracker red expressions of MBCs and their subgroups demonstrated a significantly up-regulation. Meanwhile, the transcriptomics analysis identified mitochondrial metabolism as the predominant and pivotal mechanism underlying APS-mediated mitigation of DSS-induced colitis. Key differentially expressed genes, including B-cell linker (BLNK), aldehyde dehydrogenase 1A1 (ALDH1A1), B-cell lymphoma 6 (BCL-6), B-lymphocyte-induced maturation protein 1 (Blimp-1), paired box gene 5 (PAX5), purinergic 2 × 7 receptor (P2X7R), B Cell activation factor (BAFF), B Cell activation factor receptor (BAFFR), CD40, nuclear factor kappa-B (NF-κB), IL-6 and so on were implicated in this process. These mRNA expressions were validated through quantitative polymerase chain reaction (qPCR) and immunohistochemistry. These findings revealed that APS effectively restored MBCs and their balance to ameliorate DSS-induced colitis, which was potentially realized via promoting mitochondrial metabolism to maintain MBCs activation.

Astragali Radix: comprehensive review of its botany, phytochemistry, pharmacology and clinical application.

Astragali Radix (A. Radix) is the dried root of Astragalus membranaceus var. mongholicus (Bge) Hsiao or Astragalus membranaceus (Fisch.) Bge., belonging to the family Leguminosae, which is mainly distributed in China. A. Radix has been consumed as a tonic in China for more than 2000 years because of its medicinal effects of invigorating the spleen and replenishing qi. Currently, more than 400 natural compounds have been isolated and identified from A. Radix, mainly including saponins, flavonoids, phenylpropanoids, alkaloids, and others. Modern pharmacological studies have shown that A. Radix has anti-tumor, anti-inflammatory, immunomodulatory, anti-atherosclerotic, cardioprotective, anti-hypertensive, and anti-aging effects. It has been clinically used in the treatment of tumors, cardiovascular diseases, and cerebrovascular complications associated with diabetes with few side effects and high safety. This paper reviewed the progress of research on its chemical constituents, pharmacological effects, clinical applications, developing applications, and toxicology, which provides a basis for the better development and utilization of A. Radix.

Astragalus polysaccharides attenuate chemotherapy-induced immune injury by modulating gut microbiota and polyunsaturated fatty acid metabolism.

BACKGROUND: The damage of chemotherapy drugs to immune function and intestinal mucosa is a common side effect during chemotherapy. Astragalus polysaccharides (APS) exhibit immunomodulatory properties and are recognized for preserving the integrity of the human intestinal barrier. Nevertheless, their application and mechanisms of action in chemotherapy-induced immune damage and intestinal barrier disruption remain insufficiently explored. PURPOSE: This study delved into investigating how APS mitigates chemotherapy-induced immune dysfunction and intestinal mucosal injury, while also providing deeper insights into the underlying mechanisms. METHODS: In a chemotherapy mice model induced by 5-fluorouracil (5-Fu), the assessment of APS's efficacy encompassed evaluations of immune organ weight, body weight, colon length, and histopathology. The regulation of different immune cells in spleen was detected by flow cytometry. 16S rRNA gene sequencings, ex vivo microbiome assay, fecal microbiota transplantation (FMT), and targeted metabolomics analysis were applied to explore the mechanisms of APS effected on chemotherapy-induced mice. RESULTS: APS ameliorated chemotherapy-induced damage to immune organs and regulated immune cell differentiation disorders, including CD4+T, CD8+T, CD19+B, F4/80+CD11B+ macrophages. APS also alleviated colon shortening and upregulated the expression of intestinal barrier proteins. Furthermore, APS significantly restored structure of gut microbiota following chemotherapy intervention. Ex vivo microbiome assays further demonstrated the capacity of APS to improve 5-Fu-induced microbiota growth inhibition and compositional change. FMT demonstrated that the regulation of gut microbiota by APS could promote the recovery of immune functions and alleviate shortening of the colon length. Remarkably, APS significantly ameliorated the imbalance of linoleic acid (LA) and α-linolenic acid in polyunsaturated fatty acid (PUFA) metabolism. Further in vitro experiments showed that LA could promote splenic lymphocyte proliferation. In addition, both LA and DGLA down-regulated the secretion of NO and partially up-regulated the percentage of F4/80+CD11B+CD206+ cells. CONCLUSION: APS can effectively ameliorate chemotherapy-induced immune damage and intestinal mucosal disruption by regulating the composition of the gut microbiota and further restoring PUFA metabolism. These findings indicate that APS can serve as an adjuvant to improve the side effects such as intestinal and immune damage caused by chemotherapy.

Research progress of the effective active ingredients of Astragalus mongholicus in the treatment of diabetic peripheral neuropathy.

Diabetic peripheral neuropathy (DPN) is one of the most prevalent consequences of diabetes, with a high incidence and disability rate. The DPN's pathogenesis is extremely complex and yet to be fully understood. Persistent high glucose metabolism, nerve growth factor deficiency, microvascular disease, oxidative stress, peripheral nerve cell apoptosis, immune factors, and other factors have been implicated in the pathogenesis of DPN. Astragalus mongholicus is a commonly used plant used to treat DPN in clinical settings. Its rich chemical components mainly include Astragalus polysaccharide, Astragalus saponins, Astragalus flavones, etc., which play a vital role in the treatment of DPN. This review aimed to summarize the pathogenesis of DPN and the studies on the mechanism of the effective components of Astragalus mongholicus in treating DPN. This is of great significance for the effective use of Chinese herbal medicine and the promotion of its status and influence on the world.

[Research progress in Astragali Radix and its active ingredients in treatment of lung cancer].

Lung cancer is the leading cause of cancer death, and its effective treatment is a difficult medical problem. Lung cancer belongs to the traditional Chinese medicine(TCM) disease categories of lung accumulation, lung amassment, and overstrain cough. Rich theoretical basis and practical experience have been accumulated in the TCM treatment of lung cancer. Astragali Radix is one of the representatives of Qi-tonifying drugs. It mainly treat the lung cancer with the syndrome of Qi deficiency and pathogen stagnation, following the principle of reinforcing healthy Qi and eliminating patgogenic Qi. Astragali Radix exerts a variety of pharmacological activities in the treatment of lung cancer, including inhibiting tumor cell proliferation and promoting tumor cell apoptosis, inhibiting tumor invasion and migration, regulating the tumor microenvironment, suppressing tumor angiogenesis, modulating autophagy, inducing macrophage polarization, enhancing immunity, inhibiting immune escape, and reversing cisplatin resistance. The active ingredients of Astragali Radix in treating lung cancer include polysaccharides, saponins, and flavonoids. This study reviewed the pharmacological activities and active ingredients of Astragali Radix in the treatment of lung cancer, providing a basis for the development and utilization of Astragali Radix resources and active ingredients and the research and development of anti-tumor drugs.

The Bronchodilator Potential of Astragalus sarcocolla: An in vitro Experiment.

OBJECTIVE: To evaluate the bronchodilatory mechanism of Astragalus sarcocolla (ASE) extract on tracheal smooth muscles of rabbits. STUDY DESIGN: In-vitro experimental study. Place and Duration of the Study: The animal house of CMH Lahore Medical College, Lahore, and Institute of Dentistry, NUMS, from October 2022 to May 2023. METHODOLOGY: Six rabbits were randomly divided into four groups. After euthanising the rabbit, the trachea was carefully dissected out and stabilised in Kreb's Henseleit solution for 30 minutes and then, stimulated by acetylcholine (Ach) 1µm, under mimicked physiological conditions. Group I served as the control group with tracheal smooth muscles stabilised with 1g tension. In Group II (positive control), tracheal smooth muscles were stimulated by potassium chloride (KCl) (80 mM and 25 mM, respectively) to get maximum tracheal smooth muscle contractions. Later, the tissue was exposed to theophylline with three molar concentrations 0.2, 0.4, 0.6, and 0.8 mM, and cumulative dose response curves were formed. In Group III (ASE group), tracheal smooth muscles were stimulated by KCl (80 mM and 25 mM) and was exposed to increasing concentration of ASE. In group IV, tissue was stimulated by KCl (25 mM) and glibenclamide (3 µM), later exposed to increasing concentration of ASE to confirm the bronchodilatory mechanism. The change in isometric contraction of the tissue was recorded using the force displacement transducer connected to a PowerLab data acquisition system. Concentration response curves were drawn, and median effective concentrations (EC50 values) and percentage inhibition were calculated. Non-linear regression was applied for the analysis of the concentration-response curves. RESULTS: ASE inhibited the KCl-induced low potassium (25 mM) contractions (EC50 = 0.38 mg/ml, 95% CI: 0.04 - 0.38, n = 6). It only partially inhibited the high potassium-induced contractions in tracheal smooth muscles. Pretreatment with glibenclamide showed a rightward shift of the dose-response curve. Theophylline and ASE significantly reduced the low K+ induced smooth muscle contractions in comparison to the control group (p <0.001, each). CONCLUSION: Astragalus sarcocolla extract produced bronchodilator effects through the activation of ATP sensitive potassium channels in isolated rabbit trachea. KEY WORDS: Astragalus sarcocolla, Bronchodilators, ATP-sensitive potassium channels, Effective concentration 50, Concentration response curves.

Pharmacological potential of Astragali Radix for the treatment of kidney diseases.

BACKGROUND: With the increasing prevalence of hypertension, diabetes, and obesity, the incidence of kidney diseases is also increasing, resulting in a serious public burden. Conventional treatments for kidney diseases have unsatisfactory effects and are associated with adverse reactions. Traditional Chinese medicines have good curative effects and advantages over conventional treatments for preventing and treating kidney diseases. Astragali Radix is a Chinese herbal medicine widely used to treat kidney diseases. PURPOSE: To review the potential applications and molecular mechanisms underlying the renal protective effects of Astragali Radix and its components and to provide direction and reference for new therapeutic strategies and future research and development of Astragali Radix. STUDY DESIGN AND METHODS: PubMed, Google Scholar, and Web of Science were searched using keywords, including "Astragali Radix," "Astragalus," "Astragaloside IV" (AS-IV), "Astragali Radix polysaccharide" (APS), and "kidney diseases." Reports on the effects of Astragali Radix and its components on kidney diseases were identified and reviewed. RESULTS: The main components of Astragali Radix with kidney-protective properties include AS-IV, APS, calycosin, formononetin, and hederagenin. Astragali Radix and its active components have potential pharmacological effects for the treatment of kidney diseases, including acute kidney injury, diabetic nephropathy, hypertensive renal damage, chronic glomerulonephritis, and kidney stones. The pharmacological effects of Astragali Radix are manifested through the inhibition of inflammation, oxidative stress, fibrosis, endoplasmic reticulum stress, apoptosis, and ferroptosis, as well as the regulation of autophagy. CONCLUSION: Astragali Radix is a promising drug candidate for treating kidney diseases. However, current research is limited to animal and cell studies, underscoring the need for further verifications using high-quality clinical data.

Identify production area, growth mode, species, and grade of Astragali Radix using metabolomics "big data" and machine learning.

BACKGROUND: Astragali Radix (AR) is a widely used herbal medicine. The quality of AR is influenced by several key factors, including the production area, growth mode, species, and grade. However, the markers currently used to distinguish these factors primarily focus on secondary metabolites, and their validation on large-scale samples is lacking. PURPOSE: This study aims to discover reliable markers and develop classification models for identifying the production area, growth mode, species, and grade of AR. METHODS: A total of 366 batches of AR crude slices were collected from six provinces in China and divided into learning (n = 191) and validation (n = 175) sets. Three ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) methods were developed and validated for determining 22 primary and 10 secondary metabolites in AR methanol extract. Based on the quantification data, seven machine learning algorithms, such as Nearest Neighbors and Gradient Boosted Trees, were applied to screen the potential markers and build the classification models for identifying the four factors associated with AR quality. RESULTS: Our analysis revealed that secondary metabolites (e.g., astragaloside IV, calycosin-7-O-ß-D-glucoside, and ononin) played a crucial role in evaluating AR quality, particularly in identifying the production area and species. Additionally, fatty acids (e.g., behenic acid and lignoceric acid) were vital in determining the growth mode of AR, while amino acids (e.g., alanine and phenylalanine) were helpful in distinguishing different grades. With both primary and secondary metabolites, the Nearest Neighbors algorithm-based model was constructed for identifying each factor of AR, achieving good classification accuracy (>70%) on the validation set. Furthermore, a panel of four metabolites including ononin, astragaloside II, pentadecanoic acid, and alanine, allowed for simultaneous identification of all four factors of AR, offering an accuracy of 86.9%. CONCLUSION: Our findings highlight the potential of integrating large-scale targeted metabolomics and machine learning approaches to accurately identify the quality-associated factors of AR. This study opens up possibilities for enhancing the evaluation of other herbal medicines through similar methodologies, and further exploration in this area is warranted.

Network pharmacology and experimental verification reveal the mechanism of Hedysari Radix and Curcumae Rhizoma with the optimal compatibility ratio against colitis-associated colorectal cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: The herb pair Astragali Radix (AR) and Curcumae Rhizoma (vinegar-processed, VPCR), derived from the traditional Chinese medicine (TCM) text 'Yixuezhongzhongcanxilu', have long been used to treat gastrointestinal diseases, notably colitis-associated colorectal cancer (CAC). Hedysari Radix (HR), belonging to the same Leguminosae family as AR but from a different genus, is traditionally used as a substitute for AR when paired with VPCR in the treatment of CAC. However, the optimal compatibility ratio for HR-VPCR against CAC and the underlying mechanisms remain unclear. AIM OF THE STUDY: To investigate the optimal compatibility ratio and underlying mechanisms of HR-VPCR against CAC using a combination of comparative pharmacodynamics, network pharmacology, and experimental verification. MATERIALS AND METHODS: The efficacy of different compatibility ratios of HR-VPCR against CAC was evaluated using various indicators, including the body weight, colon length, tumor count, survival rate, disease activity index (DAI) score, Haemotoxylin and Eosin (H&E) pathological sections, inflammation cytokines (IL-1ß, IL-6, IL-10, TNF-α), tumor markers (K-Ras, p53), and intestinal permeability proteins (claudin-1, E-cadherin, mucin-2). Then, the optimal compatibility ratio of HR-VPCR against CAC was determined based on the fuzzy matter-element analysis by integrating the above indicators. After high-performance liquid chromatography (HPLC) analysis for the optimal compatibility ratio of HR-VPCR, potential active components of HR-VPCR were identified by TCMSP and the previous bibliographies. Swiss Targets and GeneCards were adopted to predict the targets of the active components and the targets of CAC, respectively. Then, the common targets of HR-VPCR against CAC were obtained by Venn analysis. PPI networks were constructed in STRING. GO and KEGG enrichments were visualized by the David database. Finally, the predicted pathway was experimentally validated via Western blot. RESULTS: Various compatibility ratios of HR-VPCR demonstrated notable therapeutic effects to some extent, evidenced by improvements in body weight, colon length, tumor count, pathological symptoms (DAI score), colon and organ indexes, survival rate, and modulation of inflammation factors (IL-1ß, IL-6, IL-10, TNF-α), as well as tumor markers (K-Ras, p53), and down-regulation of intestinal permeability proteins (claudin-1, E-cadherin, mucin-2) in CAC mice. Among these ratios, the ratio 4:1 represents the optimal compatibility ratio by the fuzzy matter-element analysis. Thirty active components of HR-VPCR were carefully selected, targeting 553 specific genes. Simultaneously, 2022 targets associated with CAC were identified. 88 common targets were identified after generating a Venn plot. Following PPI network analysis, 29 core targets were established, with AKT1 ranking highest among them. Further analysis via GO and KEGG enrichment identified the PI3K-AKT signaling pathway as a potential mechanism. Experimental validation confirmed that HR-VPCR intervention effectively reversed the activated PI3K-AKT signaling pathway. CONCLUSIONS: The optimal compatibility ratio for the HR-VPCR herb pair in alleviating CAC is 4:1. HR-VPCR exerts its effects by alleviating intestinal inflammation, improving intestinal permeability, and regulating the PI3K-AKT signaling pathway.

Study of the Mechanism of Astragali Radix in Treating Type 2 Diabetes Mellitus and Its Renal Protection Based on Enzyme Activity, Network Pharmacology, and Experimental Verification.

Astragali Radix (AR) is a common Chinese medicine and food. This article aims to reveal the active role of AR in treating Type 2 diabetes mellitus (T2DM) and its renal protective mechanism. The hypoglycemic active fraction was screened by α-glucosidase and identified by UPLC-QE-Orbitrap-MS spectrometry. The targets and KEGG pathway were determined through the application of network pharmacology methodology. Molecular docking and molecular dynamics simulation technology were used for virtual verification. Subsequently, a mouse model of T2DM was established, and the blood glucose and renal function indexes of the mice after administration were analyzed to further prove the pharmacodynamic effect and mechanism of AR in the treatment of T2DM. HA was determined as the best hypoglycemic active fraction by the α-glucosidase method, with a total of 23 compounds identified. The main active components, such as calycoside-7-O-ß-D-glucoside, methylnisoline, and formononetin, were revealed by network pharmacology. In addition, the core targets and the pathway have also been determined. Molecular docking and molecular dynamics simulation techniques have verified that components and targets can be well combined. In vivo studies have shown that AR can reduce blood sugar levels in model mice, enhance the anti-inflammatory and antioxidant activities of kidney tissue, and alleviate kidney damage in mice. And it also has regulatory effects on proteins such as RAGE, PI3K, and AKT. AR has a good therapeutic effect on T2DM and can repair disease-induced renal injury by regulating the RAGE/PI3K/Akt signaling pathway. This study provides ideas for the development of new drugs or dietary interventions for the treatment of T2DM.

Study on the Biotransformation and Activities of Astragalosides from Astragali Radix In Vitro and In Vivo.

Astragalosides (AGs), as one of the main active ingredients in Astragali Radix (AR), have a series of biological activities. Previous studies have only qualitatively identified the metabolites of AGs in AR, resulting in a lack of quantification. In the present study, the original material was selected from 12 origins based on the levels of 4 AGs by high-performance liquid chromatography (HPLC). The prototype components and metabolites of total AGs (TAGs) in feces, urine, and plasma samples of rats were thoroughly screened and characterized by ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS). The fermentation reaction and metabolites were verified by human fecal TAG fermentation in vitro. The metabolites of AG I, II, and IV transformed by human feces at different times were identified using UHPLC-HRMS, and the partial metabolites were quantified by HPLC. Furthermore, the anti-inflammatory and antioxidant activities of the metabolites were evaluated based on 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells in vitro. In total, 13 AGs and 170 metabolites were identified in TAGs as well as in the plasma, urine, and feces of Sprague-Dawley (SD) rats by UHPLC-HRMS, including 28, 36, and 170 metabolites in the plasma, urine, and feces, respectively. The metabolites included the products of deglycosylation, demethylation, hydroxylation, glucuronidation, sulfation, and cysteine-binding reactions. Moreover, the TAG fermentation results in vitro showed great similarity. The human fecal incubation experiments for AG I, II, and IV demonstrated that the metabolic reaction of TAGs mainly occurred in intestinal feces and that deglycosylation, demethylation, and hydroxylation were the main pathways of their metabolism. HPLC quantitative analysis of the transformation solution at different time points showed that AGs were transformed into secondary glycosides [cycloastragenol-6-glucoside (CAG-6-glucoside)] and aglycones [cycloastragenol (CAG)] through a deglycosylation reaction. Analysis of the pharmacological activity showed that the anti-inflammatory and antioxidant activities of the metabolites were associated with the levels of the corresponding aglycones. Further, metabolic profiles of the TAGs were constructed. Overall, this study revealed the metabolic process of AGs in the intestine, providing guidance for the metabolism and pharmacological effects of other saponins.

Based on network pharmacology and molecular docking to explore the molecular mechanism of Ginseng and Astragalus decoction against postmenopausal osteoporosis.

Traditional Chinese medicine suggests that Ginseng and Astragalus Decoction (GAD) may effectively treat postmenopausal osteoporosis (PMO). However, the exact mechanism of action for GAD remains unclear. This study aims to utilize network pharmacology and molecular docking technology to explore the potential mechanism of GAD in treating PMO. The main chemical components of GAD were identified by consulting literature and traditional Chinese medicine systems pharmacology database. GeneCards and online mendelian inheritance in man were used to identify PMO disease targets, and Cytoscape 3.8.2 software was used to construct a herb-disease-gene-target network. The intersection of drug targets and disease targets was introduced into the search tool for the retrieval of interacting genes platform to construct a protein-protein interaction network. Additionally, we further conducted gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses, followed by molecular docking between active ingredients and core protein targets. We have identified 59 potential targets related to the treatment of PMO by GAD, along with 33 effective components. Quercetin and kaempferol are the compounds with higher degree. In the protein-protein interaction network, IL6, AKT1, and IL1B are proteins with high degree. The enrichment analysis of gene ontology and KEEG revealed that biological processes involved in treating PMO with GAD mainly include response to hormones, positive regulation of phosphorylation, and regulation of protein homodimerization activity. The signal pathways primarily include Pathways in cancer, PI3K-Akt signaling pathway, and AGE-RAGE signaling pathway. Molecular docking results indicate that kaempferol and quercetin have a high affinity for IL6, AKT1, and IL1B. Our research predicts that IL6, AKT1, and IL1B are highly likely to be potential targets for treating PMO with GAD. PI3K/AKT pathway and AGE-ARGE pathway may play an important role in PMO.

A Multi-Component Nano-Co-Delivery System Utilizing Astragalus Polysaccharides as Carriers for Improving Biopharmaceutical Properties of Astragalus Flavonoids.

Purpose: Enhancing the dissolution, permeation and absorption of active components with low solubility and poor permeability is crucial for maximizing therapeutic efficacy and optimizing functionality. The objective of this study is to investigate the potential of natural polysaccharides as carriers to improve the biopharmaceutical properties of active components. Methods: In this study, we employed four representative flavonoids in Astragali Radix, namely Calycosin-7-O-ß-D-glucoside (CAG), Ononin (ON), Calycosin (CA) and Formononetin (FMN), as a demonstration to evaluate the potential of Astragalus polysaccharides (APS) as carriers to improve the biopharmaceutical properties, sush as solubility, permeability, and absorption in vivo. In addition, the microstructure of the flavonoids-APS complexes was characterized, and the interaction mechanism between APS and flavonoids was investigated using multispectral technique and molecular dynamics simulation. Results: The results showed that APS can self-assemble into aggregates with a porous structure and large surface area in aqueous solutions. These aggregates can be loaded with flavonoids through weak intermolecular interactions, such as hydrogen bonding, thereby improving their gastrointestinal stability, solubility, permeability and absorption in vivo. Conclusion: We discovered the self-assembly properties of APS and its potential as carriers. Compared with introducing external excipients, the utilization of natural polysaccharides in plants as carriers may have a unique advantage in enhancing dissolution, permeation and absorption.

Residue of Chlormequat and Regulatory Effects on the Specialized Metabolites of Astragali Radix.

Presently, the utilization of chlormequat in Astragalus mongholicus Bunge (Leguminosae) cultivation is prevalent for augmenting rhizome (Astragali Radix) yield. However, indiscriminate and excessive chlormequat employment can detrimentally influence Astragali Radix quality and safety. This research aimed to comprehensively comprehend chlormequat risks and its influence on Astragali Radix metabolites. Diverse chlormequat concentrations were employed in Astragalus mongholicus cultivation, with subsequent analysis of residual chlormequat levels in Astragali Radix across treatment groups. Astragali Radix metabolic profiling was conducted through UPLC-QTOF-MS, and thirteen principal active components were quantified via UFLC-MS/MS. Findings revealed a direct correlation between chlormequat residue levels in Astragali Radix and application concentration, with high-dose residue surpassing 5.0 mg/kg. Metabolomics analysis identified twenty-six distinct saponin and flavonoid metabolites. Notably, the application of chlormequat led to the upregulation of seven saponins (e.g., astragaloside I and II) and downregulation of six flavonoids (e.g., methylnissolin-3-O-glucoside and astraisoflavan-7-O-ß-d-glucoside). Quantitative analysis demonstrated variable contents of active ingredients due to differing chlormequat concentrations, leading to astragaloside I increase (14.59-62.55%) and isoastragaloside II increase (4.8-55.63%), while methylnissolin-3-O-glucoside decreased (22.18-41.69%), as did astraisoflavan-7-O-ß-d-glucoside (21.09-47.78%). In conclusion, chlormequat application influenced multiple active components in Astragali Radix, causing constituent proportion variations. Elevated chlormequat concentrations led to increased active components alongside heightened chlormequat residues in Astragali Radix. Consequently, prudent chlormequat application during Astragali Radix production is imperative to avert potential detriments to its quality and safety.

Exploring potential targets of HPV&BC based on network pharmacology and urine proteomics.

BACKGROUND: Bladder cancer (BC) caused by Human papillomavirus (HPV) infection remains a complex public health problem in developing countries. Although the HPV vaccine effectively prevents HPV infection, it does not benefit patients with BC who already have HPV. METHODS: Firstly, the differential genes of HPV-related BC patients were screened by transcriptomics, and then the prognostic and clinical characteristics of the differential genes were analyzed to screen out the valuable protein signatures. Furthermore, the compound components and targets of Astragali Radix (AR) were analyzed by network pharmacology, and the intersection targets of drug components and HPV_BC were screened out for pathway analysis. In addition, the binding ability of the compound to the Astragali-HPV_BC target was verified by molecular docking and virtual simulation. Finally, to identify potential targets in BC patients through urine proteomics and in vitro experiments. RESULTS: Eleven HPV_BC-related protein signatures were screened out, among which high expression of EGFR, CTNNB1, MYC, GSTM1, MMP9, CXCR4, NOTCH1, JUN, CXCL12, and KRT14 had a poor prognosis, while low expression of CASP3 had a poor prognosis. In the analysis of clinical characteristics, it was found that high-risk scores, EGFR, MMP9, CXCR4, JUN, and CXCL12 tended to have higher T stage, pathological stage, and grade. Pharmacological and molecular docking analysis identified a natural component of AR (Quercetin) and it corresponding core targets (EGFR). The OB of the natural component was 46.43, and the DL was 0.28, respectively. In addition, EGFR-Quercetin has high affinity. Urine proteomics and RT-PCR showed that EGFR was expressed explicitly in BC patients. Mechanism analysis revealed that AR component targets might affect HPV_BC patients through Proteoglycans in the cancer pathway. CONCLUSION: AR can target EGFR through its active component (Quercetin), and has a therapeutic effect on HPV_BC patients.

Pharmacological Effects of Astragaloside IV: A Review.

Astragaloside IV (AS-IV) is one of the main active components extracted from the Chinese medicinal herb Astragali and serves as a marker for assessing the herb's quality. AS-IV is a tetracyclic triterpenoid saponin in the form of lanolin ester alcohol and exhibits various biological activities. This review article summarizes the chemical structure of AS-IV, its pharmacological effects, mechanism of action, applications, future prospects, potential weaknesses, and other unexplored biological activities, aiming at an overall analysis. Papers were retrieved from online electronic databases, such as PubMed, Web of Science, and CNKI, and data from studies conducted over the last 10 years on the pharmacological effects of AS-IV as well as its impact were collated. This review focuses on the pharmacological action of AS-IV, such as its anti-inflammatory effect, including suppressing inflammatory factors, increasing T and B lymphocyte proliferation, and inhibiting neutrophil adhesion-associated molecules; antioxidative stress, including scavenging reactive oxygen species, cellular scorching, and regulating mitochondrial gene mutations; neuroprotective effects, antifibrotic effects, and antitumor effects.

Differences and similarities in selenium biopathways in Astragalus, Neptunia (Fabaceae) and Stanleya (Brassicaceae) hyperaccumulators.

BACKGROUND AND AIMS: Selenium hyperaccumulator species are of primary interest for studying the evolution of hyperaccumulation and for use in biofortification because selenium is an essential element in human nutrition. In this study, we aimed to determine whether the distributions of selenium in the three most studied hyperaccumulating taxa (Astragalus bisulcatus, Stanleya pinnata and Neptunia amplexicaulis) are similar or contrasting, in order to infer the underlying physiological mechanisms. METHODS: This study used synchrotron-based micro-X-ray fluorescence (µXRF) techniques to visualize the distribution of selenium and other elements in fresh hydrated plant tissues of A. racemosus, S. pinnata and N. amplexicaulis. KEY RESULTS: Selenium distribution differed widely in the three species: in the leaves of A. racemosus and N. amplexicaulis selenium was mainly concentrated in the pulvini, whereas in S. pinnata it was primarilylocalized in the leaf margins. In the roots and stems of all three species, selenium was absent in xylem cells, whereas it was particularly concentrated in the pith rays of S. pinnata and in the phloem cells of A. racemosus and N. amplexicaulis. CONCLUSIONS: This study shows that Astragalus, Stanleya and Neptunia have different selenium-handling physiologies, with different mechanisms for translocation and storage of excess selenium. Important dissimilarities among the three analysed species suggest that selenium hyperaccumulation has probably evolved multiple times over under similar environmental pressures in the US and Australia.