Treating cancer through modulating exosomal protein loading and function: The prospects of natural products and traditional Chinese medicine.

Exosomes, small yet vital extracellular vesicles, play an integral role in intercellular communication. They transport critical components, such as proteins, lipid bilayers, DNA, RNA, and glycans, to target cells. These vesicles are crucial in modulating the extracellular matrix and orchestrating signal transduction processes. In oncology, exosomes are pivotal in tumor growth, metastasis, drug resistance, and immune modulation within the tumor microenvironment. Exosomal proteins, noted for their stability and specificity, have garnered widespread attention. This review delves into the mechanisms of exosomal protein loading and their impact on tumor development, with a focus on the regulatory effects of natural products and traditional Chinese medicine on exosomal protein loading and function. These insights not only offer new strategies and methodologies for cancer treatment but also provide scientific bases and directions for future clinical applications.

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.

Use of Transcriptome Sequencing to Analyze the Effects of Different Doses of an Astragalus-Rhubarb-Saffron Mixture in Mice with Diabetic Kidney Disease.

Purpose: To investigate the therapeutic effect and underlying mechanism of a traditional Chinese medicine (TCM) mixture consisting of Astragalus, rhubarb, and saffron in a mouse model of diabetic kidney disease (DKD). Methods: Forty-eight db/db mice received no TCM (DKD model), low-dose TCM, medium-dose TCM, or high-dose TCM, and an additional 12 db/m mice received no TCM (normal control). Intragastric TCM or saline (controls) was administered daily for 24 weeks. Blood glucose, body weight, serum creatinine (SCr), blood urea nitrogen (BUN), blood lipids, and urinary microalbumin were measured every four weeks, and the urinary albumin excretion rate (UAER) was calculated. After 24 weeks, kidney tissues were collected for transcriptome sequencing, and the main functions of these genes were determined via functional enrichment analysis. Results: Compared with the DKD model group, the medium-dose and high-dose TCM groups had significantly decreased levels of SCr, BUN, total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and UAER (all p<0.05). We identified 42 genes that potentially functioned in this therapeutic response, and the greatest effect on gene expression was in the high-dose TCM group. We also performed functional enrichment analysis to explore the potential mechanisms of action of these different genes. Conclusion: A high-dose of the Astragalus-rhubarb-saffron TCM provided the best prevention of DKD. Analysis of the kidney transcriptome suggested that this TCM mixture may prevent DKD by altering immune responses and oxygen delivery by hemoglobin.

Genome-Wide Analysis of the HSF Gene Family Reveals Its Role in Astragalus mongholicus under Different Light Conditions.

Astragalus mongholicus is a traditional Chinese medicine (TCM) with important medicinal value and is widely used worldwide. Heat shock (HSF) transcription factors are among the most important transcription factors in plants and are involved in the transcriptional regulation of various stress responses, including drought, salinity, oxidation, osmotic stress, and high light, thereby regulating growth and developmental processes. However, the HFS gene family has not yet been identified in A. mongholicus, and little is known regarding the role of HSF genes in A. mongholicus. This study is based on whole genome analysis of A. mongholicus, identifying a total of 22 AmHSF genes and analyzing their physicochemical properties. Divided into three subgroups based on phylogenetic and gene structural characteristics, including subgroup A (12), subgroup B (9), and subgroup C (1), they are randomly distributed in 8 out of 9 chromosomes of A. mongholicus. In addition, transcriptome data and quantitative real time polymerase chain reaction (qRT-PCR) analyses revealed that AmHSF was differentially transcribed in different tissues, suggesting that AmHSF gene functions may differ. Red and blue light treatment significantly affected the expression of 20 HSF genes in soilless cultivation of A. mongholicus seedlings. AmHSF3, AmHSF3, AmHSF11, AmHSF12, and AmHSF14 were upregulated after red light and blue light treatment, and these genes all had light-corresponding cis-elements, suggesting that AmHSF genes play an important role in the light response of A. mongholicus. Although the responses of soilless-cultivated A. mongholicus seedlings to red and blue light may not represent the mature stage, our results provide fundamental research for future elucidation of the regulatory mechanisms of HSF in the growth and development of A. mongholicus and its response to different light conditions.

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.

Research progress of astragaloside IV in treating acute kidney injury.

Acute kidney injury (AKI) is one of the most common clinical critical illnesses, with decreased glomerular filtration rate, retention of nitrogen products, water and electrolyte disorders, and acid-base imbalance as the main clinical manifestations. Presently, there is no effective treatment for acute kidney injury, but the main treatment is to cure the primary disease, remove risk factors, maintain acid-base and water-electrolyte balance, and undergo kidney replacement. However, the mortality rate is still high. Investigations and studies showed that the mortality rate of patients with acute kidney injury in the ICU is 5-80% [1]. In recent years, Chinese medicine has been widely used in acute kidney injury treatment due to its complete dialectical system and rich experience. Astragalus is a commonly used medicine in traditional Chinese medicine to treat acute kidney injury. Astragaloside IV is the main active component of traditional Chinese medicine, Astragalus membranaceus. This article summarizes the relevant studies on treating acute kidney injury with astragaloside IV.

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.

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.

Phenolic Compound Profiles, Cytotoxic, Antioxidant, Antimicrobial Potentials and Molecular Docking Studies of Astragalus gymnolobus Methanolic Extracts.

Since Astragalus is a genus with many important medicinal plant species, the present work aimed to investigate the phytochemical composition and some biological activities of Astragalus gymnolobus. The methanolic fractions of four organs (stems, flowers, leaves, root and whole plant) were quantified and identified by Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometry (LC-ESI-MS/MS) analysis. Hesperidin, hyperoside, p-hydroxybenzoic acid, protocatechuic acid and p-coumaric acid were identified as main compounds among the extracts. Among all cells, leaf methanol (Lm) extract had the highest cytotoxic effect on HeLa cells (IC50 = 0.069 µg/mL). Hesperidin, the most abundant compound in A. gymnolobus extract, was found to show a strong negative correlation with the cytotoxic effect observed in HeLa cells according to Pearson correlation test results and to have the best binding affinity to targeted proteins by docking studies. The antimicrobial activity results indicated that the most susceptible bacterium against all extracts was identified as Streptococcus pyogenes with 9-11 mm inhibition zone and 8192 mg/mL MIC value. As a result of the research, it was suggested that A. gymnolobus could be considered as a promising source that contributes to the fight against cancer.

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.

Analysis of Microbial Diversity and Community Structure of Rhizosphere Soil of Three Astragalus Species Grown in Special High-Cold Environment of Northwestern Yunnan, China.

Astragalus is a medicinal plant with obvious rhizosphere effects. At present, there are many Astragalus plants with high application value but low recognition and resource reserves in the northwestern area of Yunnan province, China. In this study, metagenomics was used to analyze the microbial diversity and community structure of rhizosphere soil of A. forrestii, A. acaulis, and A. ernestii plants grown in a special high-cold environment of northwestern Yunnan, China, at different altitudes ranging from 3225 to 4353 m. These microbes were taxonomically annotated to obtain 24 phyla and 501 genera for A. forrestii, 30 phyla and 504 genera for A. acaulis, as well as 39 phyla and 533 genera for A. ernestii. Overall, the dominant bacterial phyla included Proteobacteria, Actinobacteria, and Acidobacteria, while the dominant fungal ones were Ascomycota and Basidiomycota. At the genus level, Bradyrhizobium, Afipia, and Paraburkholderia were the most prevalent bacteria, and Hyaloscypha, Pseudogymnoascus, and Russula were the dominant fungal genera. Some of them are considered biocontrol microbes that could sustain the growth and health of host Astragalus plants. Redundancy analysis revealed that pH, TN, and SOM had a significant impact on the microbial community structures (p < 0.05). Finally, triterpene, flavonoid, polysaccharide, and amino acid metabolisms accounted for a high proportion of the enriched KEGG pathways, which possibly contributed to the synthesis of bioactive constituents in the Astragalus plants.

Prediction of potential targets and toxicological insights of Astragalus in liver cancer based on network pharmacology: Integrating systems biology, drug interaction networks, and toxicological perspectives.

This study investigates Astragalus's efficacy as a novel therapeutic option for primary liver cancer (PLC), capitalizing on its anti-inflammatory and antiviral effects. We utilized network pharmacology to unveil Astragalus's potential targets against PLC, revealing significant gene expression alterations in treated samples-20 genes were up-regulated, and 20 were down-regulated compared to controls. Our analysis extended to single-cell resolution, where we processed scRNA-seq data to discern 15 unique cell clusters within the immune, malignant, and stromal compartments through advanced algorithms like UMAP and tSNE. To delve deeper into the functional implications of these gene expression changes, we conducted comprehensive gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses, alongside Gene Set Variation Analysis, to elucidate the biological processes and pathways involved. Further, we constructed protein-protein interaction networks to visualize the intricate molecular interplay, highlighting the down-regulation of MT1E in PLC cells, a finding corroborated by quantitative polymerase chain reaction. Molecular docking studies affirmed the potent interaction between Astragalus's active compounds and MT proteins, underscoring a targeted therapeutic mechanism. Our investigation also encompassed a detailed cellular landscape analysis, identifying nine cell subgroups related to MT1 expression and specifying five cell subsets through the SingleR package. Advanced trajectory and cell-cell interaction analyses offered deeper insights into the dynamics of MT1-associated cellular subpopulations. This comprehensive methodology not only underpins Astragalus's promising role in PLC treatment but also advances our understanding of its molecular and cellular mechanisms, paving the way for targeted therapeutic strategies.

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.

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.

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.

Astragalus polysaccharide improves diabetic ulcers by promoting M2-polarization of macrophages to reduce excessive inflammation via the ß-catenin/ NF-κB axis at the late phase of wound-healing.

Ethnopharmacological relevance: Astragalus polysaccharide (APS), the most biologically active ingredient of Astragali Radix, is used to treat diabetes mellitus (DM)-related chronic wounds in traditional Chinese medicine for several decades. This herb possesses an anti-inflammatory effect. Our study proved that APS can reduce excessive inflammation at the late phase of wound-healing in diabetic ulcers. Aim of the study: To clarify the molecular mechanism of APS in promoting wound-healing via reducing excessive inflammation in diabetic ulcers during the late stages of wound-healing. Methods and materials: The rat model of the diabetic ulcers was established via intraperitoneal injection of streptozocin (60 mg/kg). We detected the regulation of APS on diabetic ulcers by measuring wound-healing rates. Bioinformatics was used to predict the target genes of APS, and autodocking was used to predict the combination of APS and target genes. Immunohistochemistry, Enzyme-linked immunosorbent assay, Western blot, immunofluorescence staining, flow cytometry, and flow cytometric sorting were investigated. Results: The results demonstrated that APS promoted wound-healing and inhibited excessive inflammation at the late phase of wound-healing in diabetic rats. Mechanistic findings showed that APS promoted the expression of ß-catenin and Rspo3 while inhibiting the expression of NF-KB and GSK-3ß, which leads to the transformation of M1-type macrophages into M2-type macrophages and thus reducing excessive inflammation at the late phase of wound-healing in diabetic ulcers. Conclusion: We found an interesting finding that APS promoted the polarization of macrophages towards M2-type through the ß-catenin/NF-κB axis to reduce excessive inflammation at the late phase of wound-healing. Therefore, APS may be a promising drug for treating diabetic ulcers in clinic.

Astragalus Polysaccharide Promotes Neuronal Injury Repair via the Notch1/NFκB Signaling Axis in the Ventroposterior Thalamic Nucleus in Rats with Focal Cerebral Ischemia.

BACKGROUND: Ischemic stroke is the most common form of stroke and the second most common cause of death and incapacity worldwide. Its pathogenesis and treatment have been the focus of considerable research. In traditional Chinese medicine, the root of Mongolian astragalus has been important in the treatment of stroke since ancient times. Astragalus polysaccharide (APS) is a key active ingredient of astragalus and offers therapeutic potential for conditions affecting the neurological system, the heart, cancer, and other disorders. However, it is not yet known how APS works to protect against ischemic stroke. METHODS: Rats were subjected to middle cerebral artery occlusion (MCAO) to imitate localized cerebral ischemia. Each of four experimental groups (normal, sham, MCAO, and MCAO+APS) contained 12 adult male Sprague-Dawley (SD) rats selected randomly from a total of 48 rats. Following successful establishment of the model, rats in the MCAO+APS group received intraperitoneal injection of APS (50 mg/kg) once daily for 14 days, whereas all other groups received no APS. The Bederson nerve function score and the forelimb placement test were used to detect motor and sensory function defects, while Nissl staining was used to investigate pathological defects in the ventroposterior thalamic nucleus (VPN). Immunohistochemical staining and Western blot were used to evaluate the expression of Neurogenic locus notch homolog protein 1 (Notch1), hairy and enhancer of split 1 (Hes1), phospho-nuclear factor-κB p65 (p-NFκB p65), and nuclear factor-κB p65 (NFκB p65) proteins in the VPN on the ischemic side of MCAO rats. RESULTS: APS promoted the recovery of sensory and motor function, enhanced neuronal morphology, increased the number of neurons, and inhibited the expression of Notch1/NFκB signaling pathway proteins in the VPN of rats with cerebral ischemia. CONCLUSION: After cerebral ischemia, APS can alleviate symptoms of secondary damage to the VPN, which may be attributed to the suppression of the Notch1/NFκB pathway.

Chinese herb couple against diabetes: integrating network pharmacology and mechanism study.

Cassia twig is a dry twig of Cinnamomum cassia Presl, a Lauraceae plant. Astragalus L is one of the largest genuses of flowering plants in the Leguminosae family. Roots of A. membranaceus Bge. var. mongholicus (Bge.) Hsiao, A. membranaceus (Fisch.) Bge. Chinese herb couple refers to the matching of two herbs in pairs, mostly with synergistic effects or toxicity reduction. This Chinese herb couple (Cassia twig-Astragalus) come from the classic famous book "Zhang Xichun's book on Chinese herb couple", which is widely used to treat diabetes. Moreover, both Cassia twig and Astragalus belong to the homology of medicine and food. However, its mechanism is still unclear. The study identified the effective components of Cassia twig-Astragalus by UPLC-Q-TOF-MS/MS and investigated the mechanism of Cassia twig-Astragalus in treating diabetes by virtue of network pharmacology, molecular docking and experimental verification. Firstly, based on UPLC-Q-TOF-MS/MS and network pharmacology, a total of 10 active ingredients of Astragalus and 6 active ingredients of Cassia twig were screened, and a total of 13 key targets were obtained. There were 64 targets at the intersection of Cassia twig-Astragalus with diabetes, mainly including IL-17, TNF, NF-κß, AGE-RAGE signaling pathway, etc. It mainly involves the response of cells to insulin stimulation, the response to insulin and the positive regulation of cell adhesion. Secondly, molecular docking results showed that quercetin has good binding activities with AKT1 and TNF. Calycosin has good binding activities with AKT1, TNF and CAV1. Formononetin has good binding activities with TNF and IL-6. Isorhamnetin has good binding activities with AKT1, TNF and IL-6. Finally, the animal experiments showed that Cassia twig-Astragalus could improve the body weight, blood glucose and glucose tolerance in diabetic rats. After the intervention with Cassia twig-Astragalus, the inflammatory factors (IL-10, TNF-α, IL-6) were significantly improved in diabetic rats, which also effectively reduced TG and TC.Communicated by Ramaswamy H. Sarma.

Integrated Transcriptomics and Metabolomics Analysis Reveals the Effects of Cutting on the Synthesis of Flavonoids and Saponins in Chinese Herbal Medicine Astragalus mongholious.

Astragali Radix, derived from the roots of Astragalus mongholicus, is a traditional Chinese medicine containing flavonoids and saponins as its key ingredients. With a shortage in the wild sources of the herbal plant, it is especially important to explore a cultivation mode for A. mongholicus for medicinal purposes. Cutting, a physical environmental stress method, was used in this study with the objective of improving the quality of this herbal legume. We found that cutting of the top 1/3 of the aboveground part of A. mongholicus during the fruiting period resulted in a significant increase in the content of flavonoids and saponins, as well as in root growth, including length, diameter, and dry weight. Furthermore, the leaves were sampled and analyzed using a combined transcriptome and metabolome analysis approach at five different time points after the treatment. Sixteen differentially expressed unigenes (DEGs) involved in the biosynthesis of flavonoids were identified; these were found to stimulate the synthesis of flavonoids such as formononetin and calycosin-7-O-ß-D-glucoside. Moreover, we identified 10 DEGs that were associated with the biosynthesis of saponins, including astragaloside IV and soyasaponin I, and found that they only regulated the mevalonic acid (MVA) pathway. These findings provide new insights into cultivating high-quality A. mongholicus, which could potentially alleviate the scarcity of this valuable medicinal plant.

Antidepressant potential of total flavonoids from Astragalus in a chronic stress mouse model: Implications for myelination and Wnt/ß-catenin/Olig2/Sox10 signaling axis modulation.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix Astragali, a versatile traditional Chinese medicinal herb, has a rich history dating back to "Sheng Nong's herbal classic". It has been employed in clinical practice to address various ailments, including depression. One of its primary active components, total flavonoids from Astragalus (TFA), remains unexplored in terms of its potential antidepressant properties. This study delves into the antidepressant effects of TFA using a mouse model subjected to chronic unpredictable mild stress (CUMS). AIMS OF THE STUDY: The study aimed to scrutinize how TFA influenced depressive behaviors, corticosterone and glutamate levels in the hippocampus, as well as myelin-related protein expression in CUMS mice. Additionally, it sought to explore the involvement of the Wnt/ß-catenin/Olig2/Sox10 signaling axis as a potential antidepressant mechanism of TFA. MATERIALS AND METHODS: Male C57BL/6 mice were subjected to CUMS to induce depressive behaviors. TFA were orally administered at two different doses (50 mg/kg and 100 mg/kg). A battery of behavioral tests, biochemical analyses, immunohistochemistry, UPLC-MS/MS, real-time PCR, and Western blotting were employed to evaluate the antidepressant potential of TFA. The role of the Wnt/ß-catenin/Olig2/Sox10 signaling axis in the antidepressant mechanism of TFA was validated through MO3.13 cells. RESULTS: TFA administration significantly alleviated depressive behaviors in CUMS mice, as evidenced by improved sucrose preference, reduced immobility in tail suspension and forced swimming tests, and increased locomotor activity in the open field test. Moreover, TFA effectively reduced hippocampal corticosterone and glutamate levels and promoted myelin formation in the hippocampus of CUMS mice. Then, TFA increased Olig2 and Sox10 expression while inhibiting the Wnt/ß-catenin pathway in the hippocampus of CUMS mice. Finally, we further confirmed the role of TFA in promoting myelin regeneration through the Wnt/ß-catenin/Olig2/Sox10 signaling axis in MO3.13 cells. CONCLUSIONS: TFA exhibited promising antidepressant effects in the CUMS mouse model, facilitated by the restoration of myelin sheaths and regulation of corticosterone, glutamate, Olig2, Sox10, and the Wnt/ß-catenin pathway. This research provides valuable insights into the potential therapeutic application of TFA in treating depression, although further investigations are required to fully elucidate the underlying molecular mechanisms and clinical relevance.