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Background: To anticipate the potential molecular mechanism of Astragalus membranaceus (AM) and its monomer, Calycosin, against peritoneal fibrosis (PF) and related muscle atrophy using mRNA-seq, network pharmacology, and serum pharmacochemistry. Methods: Animal tissues were examined to evaluate a CKD-PF mice model construction. mRNA sequencing was performed to find differential targets. The core target genes of AM against PF were screened through network pharmacology analysis, and CKD-PF mice models were given high- and low-dose AM to verify common genes. Serum pharmacochemistry was conducted to clarify which components of AM can enter the blood circulation, and the selected monomer was further validated through cell experiments for the effect on PF and mesothelial mesenchymal transition (MMT) of peritoneal mesothelial cells (PMCs). Results: The CKD-PF mice models were successfully constructed. A total of 31,184 genes were detected in the blank and CKD-PF groups, and 228 transcription factors had significant differences between the groups. Combined with network pharmacology analysis, a total of 228 AM-PF-related targets were identified. Androgen receptor (AR) was the remarkable transcription factor involved in regulating transforming growth factor-ß1 (TGF-ß1). AM may be involved in regulating the AR/TGF-ß1 signaling pathway and may alleviate peritoneal dialysis-related fibrosis and muscle atrophy in CKD-PF mice. In 3% peritoneal dialysis solution-stimulated HMrSV5 cells, AR expression levels were dramatically reduced, whereas TGF-ß1/p-smads expression levels were considerably increased. Conclusion: AM could ameliorate PF and related muscle atrophy via the co-target AR and modulated AR/TGF-ß1 pathway. Calycosin, a monomer of AM, could partially reverse PMC MMT via the AR/TGF-ß1/smads pathway. This study explored the traditional Chinese medicine theory of "same treatment for different diseases," and supplied the pharmacological evidence of "AM can treat flaccidity syndrome."

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BACKGROUND: Diabetic kidney disease (DKD) is the primary cause of end-stage renal disease. The Astragalus-Coptis drug pair is frequently employed in the management of DKD. However, the precise molecular mechanism underlying its therapeutic effect remains elusive. AIM: To investigate the synergistic effects of multiple active ingredients in the Astragalus-Coptis drug pair on DKD through multiple targets and pathways. METHODS: The ingredients of the Astragalus-Coptis drug pair were collected and screened using the TCMSP database and the SwissADME platform. The targets were predicted using the SwissTargetPrediction database, while the DKD differential gene expression analysis was obtained from the Gene Expression Omnibus database. DKD targets were acquired from the GeneCards, Online Mendelian Inheritance in Man database, and DisGeNET databases, with common targets identified through the Venny platform. The protein-protein interaction network and the "disease-active ingredient-target" network of the common targets were constructed utilizing the STRING database and Cytoscape software, followed by the analysis of the interaction relationships and further screening of key targets and core active ingredients. Gene Ontology (GO) function and Kyoto Ency-clopedia of Genes and Genomes (KEGG) pathway enrichments were performed using the DAVID database. The tissue and organ distributions of key targets were evaluated. PyMOL and AutoDock software validate the molecular docking between the core ingredients and key targets. Finally, molecular dynamics (MD) simulations were conducted to simulate the optimal complex formed by interactions between core ingredients and key target proteins. RESULTS: A total of 27 active ingredients and 512 potential targets of the Astragalus-Coptis drug pair were identified. There were 273 common targets between DKD and the Astragalus-Coptis drug pair. Through protein-protein interaction network topology analysis, we identified 9 core active ingredients and 10 key targets. GO and KEGG pathway enrichment analyses revealed that Astragalus-Coptis drug pair treatment for DKD involves various biological processes, including protein phosphorylation, negative regulation of apoptosis, inflammatory response, and endoplasmic reticulum unfolded protein response. These pathways are mainly associated with the advanced glycation end products (AGE)-receptor for AGE products signaling pathway in diabetic complications, as well as the Lipid and atherosclerosis. Molecular docking and MD simulations demonstrated high affinity and stability between the core active ingredients and key targets. Notably, the quercetin-AKT serine/threonine kinase 1 (AKT1) and quercetin-tumor necrosis factor (TNF) protein complexes exhibited exceptional stability. CONCLUSION: This study demonstrated that DKD treatment with the Astragalus-Coptis drug pair involves multiple ingredients, targets, and signaling pathways. We propose a novel approach for investigating the molecular mechanism underlying the therapeutic effects of the Astragalus-Coptis drug pair on DKD. Furthermore, we suggest that quercetin is the most potent active ingredient and specifically targets AKT1 and TNF, providing a theoretical foundation for further exploration of pharmacologically active ingredients and elucidating their molecular mechanisms in DKD treatment.

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Background: This pragmatic clinical trial aims to determine the efficacy and safety of add-on Astragalus membranaceus (AM) for cognition and non-cognition in patients with of mild to moderate Alzheimer's disease complicated with orthostatic hypotension in orthostatic hypotension, elucidate the underlying mechanisms, identify related response predictors, and explore effective drug components. Methods: This is an add-on, assessor-blinded, parallel, pragmatic, randomized controlled trial. At least 66 adults with mild to moderate Alzheimer's disease (AD) and OH aged 50-85 years will be recruited. Participants will be randomized in a 1:1:1 ratio to receive 24 weeks of routine care or add-on low dose AM or add-on high dose AM group. The primary efficacy outcome will be measured by the Alzheimer's Disease Assessment Scale-Cognitive Subscale, Chinese version. Secondary efficacy outcome assessment will include neuropsychological tests, blood pressure, plasma biomarkers, multimodal electroencephalograms, and neuroimaging. Safety outcome measures will include physical examinations, vital signs, electrocardiography, laboratory tests (such as hematologic and blood chemical tests), and adverse event records. Ethics and dissemination: This trial was approved and supervised by Fujian Medical University Union Hospital (2021KJCX040). Independent results, findings will be published in peer-reviewed journals and presented at national and international conferences. Trial registration number: NCT05647473; ClinicalTrials.gov Identifier.

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Astragalus membranaceus (A. membranaceus) leaves can be used both as a medicine and food material. Their main chemical components are flavonoids and triterpenoid saponins. The pharmacokinetics of A. membranaceus leaves are rarely reported in the literature. This study aimed to investigate the pharmacokinetics of five major bioactive components of A. membranaceus leaves [rhamnocitrin 3-glucoside (RCG), tiliroside (TIL), rhamnocitrin 3-neohesperidoside (RNH), huangqiyenin R (HuR), and huangqiyenin I (HuI)]. Simultaneously using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method. The extract of A. membranaceus leaves was administered orally to rats, and the rat plasma was subjected to a fast, sensitive, and specific UHPLC-MS/MS method. Butylparaben served as the internal standard. The plasma samples were pretreated using isopropanol/ethyl acetate (1:1, v/v) liquid-liquid extraction. Chromatographic separations were performed at a flow rate of 0.3 mL/min on a Waters ACQUITY HSS T3 Column (2.1 mm × 100 mm, 1.8 µm) using mobile phases of 0.1 % formic acid/water and 0.1 % formic acid/acetonitrile. Mass spectrometry detection was performed using an electrospray ionization ion source in the negative-ion mode and the multiple reaction monitoring mode. All analytes had an intraday and interday relative standard deviation of less than 14.10 %. The range of accuracy was -11.94-6.920 % and -15.22-5.800 %. The lower limits of quantification for RCG, TIL, RNH, HuR, HuI was 10.24, 10.27, 10.12, 5.137, and 5.841 ng/mL, respectively. The criteria were met by stability, matrix effects, and extraction recovery. The pharmacokinetic parameters of A. membranaceus leaf extract were ultimately obtained using this analytical method. The study provides a theoretical basis for future pharmacological research, clinical application, and development of healthy food from A. membranaceus leaves.

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Astragalus propinquus , Flavonoides , Hojas de la Planta , Ratas Sprague-Dawley , Saponinas , Espectrometría de Masas en Tándem , Triterpenos , Espectrometría de Masas en Tándem/métodos , Cromatografía Líquida de Alta Presión/métodos , Hojas de la Planta/química , Animales , Flavonoides/farmacocinética , Flavonoides/sangre , Flavonoides/análisis , Saponinas/farmacocinética , Saponinas/sangre , Saponinas/análisis , Ratas , Triterpenos/farmacocinética , Triterpenos/sangre , Triterpenos/análisis , Masculino , Extractos Vegetales/farmacocinética , Extractos Vegetales/química , Medicamentos Herbarios Chinos/farmacocinética , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/análisis , Administración Oral , Reproducibilidad de los Resultados

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Astragaloside IV is a significant chemical component derived from the medicinal plant Astragalus membranaceus. Despite the characterization of several glycosyltransferases from A. membranaceus, the complete biosynthetic pathway of astragaloside IV has not been fully elucidated. In this study, we propose a biosynthetic pathway for astragaloside IV that involves a sequence of oxidation-reduction reactions. The biosynthesis pathway from cycloastragenol to astragaloside IV encompasses four key steps: C-3 oxidation, 6-O-glucosylation, C-3 reduction, and 3-O-xylosylation. We identified a hydroxysteroid dehydrogenase AmHSD1 from A. membranaceus. AmHSD1 catalyzes the C-3 oxidation of cycloastragenol, yielding cycloastragenol-3-one, and the C-3 reduction of cycloastragenol-3-one-6-O-glucoside, resulting in cycloastragenol-6-O-glucoside. Additionally, the glycosyltransferases AmGT8 and AmGT1, previously reported by our groups, were identified as catalyzing the 6-O-glucosylation and 3-O-xylosylation steps, respectively. Astragaloside IV was successfully synthesized in transient expression in Nicotiana benthamiana using the combination of AmHSD1, AmGT8 and AmGT1. These results support the proposed four-step biosynthetic pathway and suggest that AmHSD1 probably plays a crucial role in the biosynthesis of astragaloside IV within A. membranaceus.

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Plants are the source of numerous remedies in modern medicine, and some of them have been studied due to their potential immunomodulatory activity. Astragalus membranaceus Fisch. ex Bunge (A. membranaceus), Nigella sativa L. (N. sativa), and Perilla frutescens (L.) Britton (P. frutescens) are plant species used in traditional medicine for the treatment of various diseases. Their potential to act as immunomodulatory, anti-inflammatory, and anti-allergic agents makes them interesting for investigating their clinical potential in alleviating the symptoms of allergic diseases. Allergy affects a large number of people; according to some sources more than 30% of the world population suffer from some type of allergic reaction, with pollen allergy as the most common type. Treatment is usually pharmacological and may not be completely effective or have side effects. Thus, we are seeking traditional medicine, mostly medicinal plants, with promising potential for alleviating allergy symptoms. A literature overview was conducted employing databases such as Scopus, PubMed, Web of Science, Springer, and Google Scholar. This manuscript summarizes recent in vivo preclinical and clinical studies on three species with immunomodulatory activity, provides a comparison of their anti-allergic effects, and underlines the potential of their application in clinical practice. The obtained results confirmed their efficacy in the in vivo and clinical studies, but also emphasize the problem of phytochemical characterization of the species and difference between tested doses. More clinical trials with standardized protocols (defined active molecules, dosage, side effects) are required to obtain safe and effective herbal drugs.

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Astragalus membranaceus Fisch. ex Bunge (syn. Astragalus mongholicus Bunge) is one of the notable medicinal and food plants. Therefore, the aim of this study was to calculate the phenolic composition and antioxidant, antimicrobial, as well as enzyme inhibitory [acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and tyrosinase (TYR)] activities with chemometric approaches of the hydromethanolic and water extracts of commercial A. membranaceus samples. Ten individual phenolic compounds were determined using high-performance liquid chromatography (HPLC), and only quercetin was found at a level of above 80 µg/g DW in both extracts. Moreover, the highest antioxidant activity in DPPH, FRAP, ABTS, and CUPRAC assays was found in the sample containing the roots in loose form from USA. A. membranaceus extracts displayed the inhibition zone diameters within the range from 10 to 22 mm antimicrobial activity against S. aureus, while there were no inhibition zones in any extracts in case of E. coli. The extracts of A. membranaceous showed an inhibition rate below 40% against TYR, and among tested extracts, only two samples were able to inhibit BChE with IC50 values of above 30 µg/mL. Correlation analysis showed a highly positive relationship between their phenolic composition and antioxidant activity. Concluding, the obtained results confirmed that A. membranaceus commercial samples could be an important dietary source of natural antioxidants.

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Astragali radix (AR, namded Huangqi in Chinese) is the dried root of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao or Astragalus membranaceus (Fisch.) Bge. As a widely used ethnomedicine, the biological activities of AR include immunomodulatory, anti-hyperglycemic, anti-oxidant, anti-aging, anti-inflammatory, anti-viral, anti-tumor, cardioprotective, and anti-diabetic effects, with minimum side effects. Currently, it is known that polysaccharides, saponins, and flavonoids are the indispensable components of AR. In this review, we will elaborate the research advancements of AR on ethnobotany, ethnopharmacological practices, phytochemicals, pharmacological activities, clinical uses, quality control, production developments, and toxicology. The information is expected to assist clinicians and scientists in developing useful therapeutic medicines with minimal systemic side effects.

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Background: Maintaining a normal range of muscle mass and function is crucial not only for sustaining a healthy life but also for preventing various disorders. Numerous nutritional or natural resources are being explored for their potential muscle hypertrophic properties. Aim: We aimed to evaluate the muscle hypertrophic effects of APX, a 1:1 mixture of Astragalus membranaceus and Paeonia japonica. In addition to the myotube differentiation cell assay, we utilized a weighted exercise-based animal model and evaluated changes in muscle hypertrophy using dual-energy X-ray absorptiometry (DXA) and histological analysis. Results: The 8-week treadmill exercise led to notable decreases in body weight and fat mass but an increase in muscle mass compared to the control group. Administration of APX significantly accelerated muscle mass gain (p < 0.05) without altering body weight or fat mass compared to the exercise-only group. This muscle hypertrophic effect of APX was consistent with the histologic size of muscle fibers in the gastrocnemius (p > 0.05) and rectus femoris (p < 0.05), as well as the regulation of myogenic transcription factors (MyoD and myogenin), respectively. Furthermore, APX demonstrated a similar action to insulin-like growth factor 1, influencing the proliferation of C2C12 myoblast cells (p < 0.01) and their differentiation into myotubes (p < 0.05) compared to the control group. Conclusion: The present study provides experimental evidence that APX has muscle hypertrophic effects, and its underlying mechanisms would involve the modulation of MyoD and myogenin.

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Background: Persistent post-infectious symptoms, predominantly fatigue, characterize Long COVID. This study investigated the efficacy of Myelophil (MYP), which contains metabolites extracted from Astragalus membranaceus and Salvia miltiorrhiza using 30% ethanol, in alleviating fatigue among subjects with Long COVID. Methods: In this prospective observational study, we enrolled subjects with significant fatigue related to Long COVID, using criteria of scores of 60 or higher on the modified Korean Chalder Fatigue scale (mKCFQ11), or five or higher on the Visual Analog Scale (VAS) for brain fog. Utilizing a single-arm design, participants were orally administered MYP (2,000 mg daily) for 4 weeks. Changes in fatigue severity were assessed using mKCFQ11, Multidimensional Fatigue Inventory (MFI-20), and VAS for fatigue and brain fog. In addition, changes in quality of life using the short form 12 (SF-12) were also assessed along with plasma cortisol levels. Results: A total of 50 participants (18 males, 32 females) were enrolled; 49 were included in the intention-to-treat analysis with scores of 66.9 ± 11.7 on mKCFQ11 and 6.3 ± 1.5 on the brain fog VAS. After 4 weeks of MYP administration, there were statistically significant improvements in fatigue levels: mKCFQ11 was measured at 34.8 ± 17.1 and brain fog VAS at 3.0 ± 1.9. Additionally, MFI-20 decreased from 64.8 ± 9.8 to 49.3 ± 10.8, fatigue VAS dropped from 7.4 ± 1.0 to 3.4 ± 1.7, SF-12 scores rose from 53.3 ± 14.9 to 78.6 ± 14.3, and plasma cortisol levels also elevated from 138.8 ± 50.1 to 176.9 ± 62.0 /mL. No safety concerns emerged during the trial. Conclusion: Current findings underline MYP's potential in managing Long COVID-induced fatigue. However, comprehensive studies remain imperative. Clinical Trial Registration: https://cris.nih.go.kr, identifier KCT0008948.

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BACKGROUND: Whether Astragalus membranaceus is an effective drug in treatment of ulcerative colitis (UC) and how it exhibit activity effect on UC is unclear. METHODS: TCMSP, GeneCards, String, and DAVID database were used to screening target genes construct PPI network and performed for GO and KEGG pathway enrichment analysis respectively. Molecular docking and animal experiment were performed. The body weight and disease activity index (DAI) of mice were recorded. ELISA kits were used to detect the levels of CAT, SOD, MDA and IL-6, IL-10, TNF-α in the blood of mice. Western blot kits were utilized to measured the expressions of MAPK14, RB1, MAPK1, JUN, ATK1, and IL2 proteins. RESULTS: The active components of Astragalus membranaceus mainly including 7-O-methylisomucronulatol, quercetin, kaempferol, formononetin and isrhamnetin. Astragalus membranaceus may inhibited the expression of TNF-α, IL-6, MDA, and promoted the expression of CAT, SOD, IL-10. The expression levels of MAPK14, RB1, MAPK1, JUN and ATK1 proteins were significantly decreased while IL2 protein increased administrated with Astragalus membranaceus. CONCLUSIONS: Astragalus membranaceus is an effective drug in treatment of UC according to related to above targets that may exhibits the anti-UC effect via its antioxidant pathway and regulating the balance of pro-inflammatory and anti-inflammatory factors.

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The rising global morbidity and mortality rates of non-small cell lung cancer (NSCLC) underscore the urgent need for more effective treatments. Current therapeutic modalities-including surgery, radiotherapy, chemotherapy, and targeted therapy-face several limitations. Recently, Astragalus membranaceus, a traditional Chinese medicine (TCM), has captured significant attention due to its broad pharmacological properties, such as immune regulation, anti-inflammatory effects, and the modulation of reactive oxygen species (ROS) and enzyme activities. This review delivers a comprehensive summary of the most recent advancements and ongoing applications of Astragalus membranaceus in NSCLC treatment, underlining its potential for integration into existing treatment protocols. It also highlights essential areas for future research, including the elucidation of its molecular mechanisms, optimization of dosage and administration, and evaluation of its efficacy and safety alongside standard therapies, all of which could potentially improve therapeutic outcomes for NSCLC patients.

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Astragalus membranaceus is a famous traditional medicinal plant. However, drought and cadmium (Cd) pollution are the main abiotic stress factors that affect plant growth and yield and the ability to improve the host's stress resistance through the use of beneficial endophytic fungi. To evaluate the tolerance of dark septate endophytes (DSE) to various abiotic stresses, 10 DSE strains [Microsphaeropsis cytisi (Mc), Alternaria alstroemeriae (Aa), Stagonosporopsis lupini (Sl), Neocamarosporium phragmitis (Np), Paraphoma chlamydocopiosa (Pc), Macrophomina phaseolina (Mp'), Papulaspora equi (Pe), Alternaria tellustris (At), Macrophomina pseudophaseolina (Mp), and Paraphoma radicina (Pr)] were investigated under different drought and Cd stressors in vitro by using solid-plate cultures and liquid-shaker cultures in the current study. The experiments involved using varying concentrations of PEG (0, 9, 18, and 27%) and Cd2+ (0, 25, 50, and 100 mg/L) to simulate different stress conditions on DSE. Additionally, the effect of DSE (Np and At) on the growth of A. membranaceus at different field water capacities (70% and 40%) and at different CdCl2 concentrations (0, 5, 10, and 15 mg Cd/kg) in soil was studied. The results demonstrated that the colony growth rates of Aa, Np, Pc, Mp', and Mp were the first to reach the maximum diameter at a PEG concentration of 18%. Aa, Np, and At remained growth-active at 100 mg Cd/L. In addition, Aa, Np, and At were selected for drought and Cd stress tests. The results of the drought-combined-with-Cd-stress solid culture indicated that the growth rate of Np was significantly superior to that of the other strains. In the liquid culture condition, the biomasses of Np and Aa were the highest, with biomasses of 1.39 g and 1.23 g under the concentration of 18% + 25 mg Cd/L, and At had the highest biomass of 1.71 g at 18% + 50 mg Cd/L concentration, respectively. The CAT and POD activities of Np reached their peak levels at concentrations of 27% + 50 mg Cd/L and 27% + 25 mg Cd/L, respectively. Compared to the control, these levels indicated increases of 416.97% and 573.12%, respectively. Aa, Np, and At positively influenced SOD activity. The glutathione (GSH) contents of Aa, Np, and At were increased under different combined stressors of drought and Cd. The structural-equation-modeling (SEM) analysis revealed that Aa positively influenced biomass and negatively affected Cd content, while Np and At positively influenced Cd content. Under the stress of 40% field-water capacity and the synergistic stress of 40% field-water capacity and 5 mg Cd/kg soil, Np and At significantly increased root weight of A. membranaceus. This study provides guidance for the establishment of agricultural planting systems and has good development and utilization value.

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BACKGROUND: In recent years, global climate change in tandem with increased human activity has resulted in habitat degradation or the migration of rare medicinal plants, potentially impacting the quality of medicinal herbs. Astragalus membranaceus var. mongholicus is a valuable bulk medicinal material in Northwest China. As the demand for this medicinal herb continues to increase in both domestic and international markets, ensuring the sustainable development of high-quality Astragali Radix is important. In this study, the maximum entropy (Maxent) model was applied, thereby incorporating 136 distribution records, along with 39 environmental factors of A. membranaceus var. mongholicus, to assess the quality zonation and potential distribution of this species in China under climate change. RESULTS: The results showed that the elevation, annual mean temperature, precipitation of wettest month, solar radiation in June, and mean temperature of warmest quarter were the critical environmental factors influencing the accumulation of astragaloside IV and Astragalus polysaccharide in A. membranaceus var. mongholicus. Among the twelve main environmental variables, annual mean temperature, elevation, precipitation of the wettest month, and solar radiation in November were the four most important factors influencing the distribution of A. membranaceus var. mongholicus. In addition, ecological niche modelling revealed that highly suitable habitats were mainly located in central and western Gansu, eastern Qinghai, northern Shaanxi, southern Ningxia, central Inner Mongolia, central Shanxi, and northern Hebei. However, the future projections under climate change suggested a contraction of these suitable areas, shifting towards northeastern high-latitude and high-elevation mountains. CONCLUSIONS: The findings provide essential insights for developing adaptive strategies for A. membranaceus var. mongholicus cultivation in response to climate change and can inform future research on this species. By considering the identified environmental factors and the potential impacts of the predicted climate changes, we can visualize the regional distribution of high-quality Radix Astragali and develop conservation strategies to protect and restore its suitable habitats.

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Astragalus propinquus , Cambio Climático , Triterpenos , China , Triterpenos/análisis , Cromatografía Líquida de Alta Presión , Saponinas/análisis , Plantas Medicinales/química , Ambiente , Temperatura , Polisacáridos/análisis

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Astragalus membranaceus saponins are the main components of A. membranaceus, a plant widely used in traditional Chinese medicine. Recently, research on the anti-cancer effects of A. membranaceus saponins has received increasing attention. Numerous in vitro and in vivo experimental data indicate that A. membranaceus saponins exhibit significant anti-cancer effects through multiple mechanisms, especially in inhibiting tumor cell proliferation, migration, invasion, and induction of apoptosis, etc. This review compiles relevant studies on the anti-cancer properties of A. membranaceus saponins from various databases over the past two decades. It introduces the mechanism of action of astragalosides, highlighting their therapeutic benefits in the management of cancer. Finally, the urgent problems in the research process are highlighted to promote A. membranaceus saponins as an effective drug against cancer.

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Apoptosis , Astragalus propinquus , Proliferación Celular , Neoplasias , Saponinas , Saponinas/farmacología , Saponinas/química , Astragalus propinquus/química , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/metabolismo , Apoptosis/efectos de los fármacos , Animales , Proliferación Celular/efectos de los fármacos , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Movimiento Celular/efectos de los fármacos

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BACKGROUND: Astragaloside IV is a main medicinal active ingredient in Astragalus membranaceus Bge. var. mongholicus (Bge.) Hsiao, which is also the key biomarker of A. membranaceus quality. Ethylene has been well-documented to involve in secondary metabolites biosynthesis in plants. Nevertheless, how ethylene regulates astragaloside IV biosynthesis in A. membranaceus is still unclear. Therefore, in the present study different dosages and time-dependent exogenous application of ethephon (Eth) were employed to analyze astragaloside IV accumulation and its biosynthesis genes expression level in hydroponically A. membranaceus. RESULTS: Exogenous 200 µmol·L- 1Eth supply is most significantly increased astragaloside IV contents in A. membranaceus when compared with non-Eth supply. After 12 h 200 µmol·L- 1 Eth treatment, the astragaloside IV contents reaching the highest content at 3 d Eth treatment(P ≤ 0.05). Moreover, After Eth treatment, all detected key genes involved in astragaloside IV synthesis were significant decrease at 3rd day(P ≤ 0.05). However, SE displayed a significant increase at the 3rd day under Eth treatment(P ≤ 0.05). Under Eth treatment, the expression level of FPS, HMGR, IDI, SS, and CYP93E3 exhibited significant negative correlations with astragaloside IV content, while expression level of SE displayed a significant positive correlation. CONCLUSIONS: These findings suggest that exogenous Eth treatment can influence the synthesis of astragaloside IV by regulating the expression of FPS, HMGR, IDI, SS, CYP93E3 and SE. This study provides a theoretical basis for utilizing molecular strategies to enhance the quality of A. membranaceus.

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BACKGROUND: The combination of Astragalus membranaceus and Carthamus tinctorius (AC) exhibits significant therapeutic effects in cerebral ischemia/reperfusion injury (CIRI). Understanding the metabolic characteristics of brain microregions and disturbances in tissues and systemic circulation is crucial for elucidating the mechanisms of CIRI and the therapeutic benefits of AC. However, in situ metabolic regulation of the complex brain structure has not been adequately studied, and the therapeutic mechanism of AC requires immediate clarification. PURPOSE: The present study aimed to unveil the specific metabolic reprogramming of CIRI at systemic and microregional levels, identify key metabolic pathways and metabolites, and elucidate the therapeutic mechanisms of AC. METHODS: Air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI), a newly developed technique, was used to investigate metabolites in brain microregions. Hematoxylin-eosin, Nissl, and immunofluorescence staining were performed to visualize the microscopic changes associated with spatial metabolism. A comprehensive metabolomics study was conducted on serum, brain tissue, and microregions, along with neurological assessments, cerebral infarction measurements, and Evans blue experiments, to assess the systemic and local metabolic effects of AC treatment for CIRI. RESULTS: AC significantly reduced neurological damage, minimized infarct size, and repaired blood-brain barrier damage in CIRI rats. AFADESI-MSI demonstrated that the metabolic imbalance caused by CIRI primarily occurs in the cerebral cortex, hippocampus, caudate putamen, thalamus, cerebellar cortex, and fiber tract regions. Significant changes in 16 metabolites were observed in these regions, corresponding to neuron damage, glial cell activation, and neural repair. 20 metabolites from serum and 4 from brain tissue varied significantly with the sham group. Comprehensive metabolomics analysis indicated a close relationship among serum, tissue, and microregional metabolism. CIRI-induced systemic and localized metabolic disorders involve 14 metabolic pathways. AC conferred therapeutic benefits in CIRI by reversing various metabolic imbalances. CONCLUSION: AFADESI-MSI efficiently visualized brain microregion metabolism. Comprehensive metabolomics analysis revealed detailed insights into the specific metabolic reprogramming in CIRI and the therapeutic impacts of AC. AC demonstrated significant clinical potential as an adjunct therapy to existing CIRI treatments.

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Astragalus propinquus , Encéfalo , Carthamus tinctorius , Metabolómica , Ratas Sprague-Dawley , Daño por Reperfusión , Animales , Carthamus tinctorius/química , Astragalus propinquus/química , Masculino , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Ratas , Isquemia Encefálica/tratamiento farmacológico , Espectrometría de Masa por Ionización de Electrospray

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Oxidative stress is proposed as a regulatory element in various neurological disorders, which is involved in the progress of several neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Antioxidant drugs are widely used to alleviate neurodegenerative disorders. Astragalus membranaceus (Huangqi, AM) is a commonly used medicinal herb with a wide range of pharmacological effects. Here, the protective effect and mechanism of AM extract (AME) and its bioactive compounds against neurodegenerative disorders via alleviating oxidative stress were detected using adult Drosophila melanogaster. The drug safety was measured by development analysis; oxidative stress resistance ability was detected by survival rate under H2O2 environment; ROS level was detected by DHE staining and gstD1-GFP fluoresence assay; antioxidative abilitiy was represent by measuring antioxidant enzyme activity, antioxidative-related gene expression, and ATP and MFN2 levels. The neuroprotective effect was evaluated by lifespan and locomotion analysis in Aß42 transgenic and Pink1B9 mutants. AME dramatically increased the survival rates, improved the CAT activity, restored the decreased mRNA expressions of Sod1, Cat, and CncC under H2O2 stimulation, and ameliorated the neurobehavioral defects of the AD and PD. Thirteen small molecules in AM had antioxidant function, in which vanillic acid and daidzein had the most potent antioxidant effect. Vanillic acid and daidzein could increase the activities of SOD and CAT, GSH level, and the expressions of antioxidant genes. Vanillic acid could improve the levels of ATP and MFN2, and mRNA expressions of ND42 and SDHC to rescue mitochondrial dysfunction. Furthermore, vanillic acid ameliorated neurobehavioral defects of PD. Daidzein ameliorated neurobehavioral defect of Aß-induced AD mode. Taken together, AM plays a protective role in oxidative damage, thereby as a potential natural drug to treat neurodegenerative disorders.

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Antioxidantes , Astragalus propinquus , Drosophila melanogaster , Enfermedades Neurodegenerativas , Estrés Oxidativo , Animales , Estrés Oxidativo/efectos de los fármacos , Astragalus propinquus/química , Drosophila melanogaster/efectos de los fármacos , Enfermedades Neurodegenerativas/tratamiento farmacológico , Enfermedades Neurodegenerativas/metabolismo , Antioxidantes/farmacología , Fármacos Neuroprotectores/farmacología , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Extractos Vegetales/farmacología , Animales Modificados Genéticamente , Medicamentos Herbarios Chinos/farmacología , Peróxido de Hidrógeno , Péptidos beta-Amiloides/metabolismo

RESUMEN

Heat shock proteins (HSPs), which function as chaperones, are activated in response to various environmental stressors. In addition to their role in diverse aspects of protein production, HSPs protect against harmful protein-related stressors. Calycosin exhibits numerous beneficial properties. This study aims to explore the protective effects of calycosin in the heart under heat shock and determine its underlying mechanism. H9c2 cells, western blot, TUNEL staining, flow cytometry, and immunofluorescence staining were used. The time-dependent effects of heat shock analyzed using western blot revealed increased HSP expression for up to 2[Formula: see text]h, followed by protein degradation after 4[Formula: see text]h. Hence, a heat shock damage duration of 4[Formula: see text]h was chosen for subsequent investigations. Calycosin administered post-heat shock demonstrated dose-dependent recovery of cell viability. Under heat shock conditions, calycosin prevented the apoptosis of H9c2 cells by upregulating HSPs, suppressing p-JNK, enhancing Bcl-2 activation, and inhibiting cleaved caspase 3. Calycosin also inhibited Fas/FasL expression and activated cell survival markers (p-PI3K, p-ERK, p-Akt), indicating their cytoprotective properties through PI3K/Akt activation and JNK inhibition. TUNEL staining and flow cytometry confirmed that calycosin reduced apoptosis. Moreover, calycosin reversed the inhibitory effects of quercetin on HSF1 and Hsp70 expression, illustrating its role in enhancing Hsp70 expression through HSF1 activation during heat shock. Immunofluorescence staining demonstrated HSF1 translocation to the nucleus following calycosin treatment, emphasizing its cytoprotective effects. In conclusion, calycosin exhibits pronounced protective effects against heat shock-induced damages by modulating HSP expression and regulating key signaling pathways to promote cell survival in H9c2 cells.

Asunto(s)

Apoptosis , Supervivencia Celular , Proteínas de Choque Térmico , Isoflavonas , Apoptosis/efectos de los fármacos , Isoflavonas/farmacología , Supervivencia Celular/efectos de los fármacos , Animales , Ratas , Proteínas de Choque Térmico/metabolismo , Proteínas de Choque Térmico/genética , Respuesta al Choque Térmico/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Línea Celular , Células Cultivadas , Caspasa 3/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo

RESUMEN

Astragalus membranaceus is a traditional Chinese medicine with multiple pharmacological activities. Modern pharmacological research has found that Astragalus membranaceus extract has an inhibitory effect on α-glucosidase, however, which component can inhibit the activity of α-glucosidase and its degree of inhibition are unknown. To address this issue, this study used affinity ultrafiltration screening combined with UPLC-ESI-Orbitrap-MS technology to screen α-glucosidase inhibitors in Astragalus membranaceus. Using affinity ultrafiltration technology, we obtained the active components, and using UPLC-ESI-Orbitrap-MS technology, we quickly analyzed and identified them. As a result, a total of 8 ingredients were selected as α-glucosidase inhibitors.