Mechanism of drug-pairs Astragalus Mongholicus-Largehead Atractylodes on treating knee osteoarthritis investigated by GEO gene chip with network pharmacology and molecular docking.

Investigations into the therapeutic potential of Astragalus Mongholicus (AM, huáng qí) and Largehead Atractylodes (LA, bái zhú) reveal significant efficacy in mitigating the onset and progression of knee osteoarthritis (KOA), albeit with an elusive mechanistic understanding. This study delineates the primary bioactive constituents and their molecular targets within the AM-LA synergy by harnessing the comprehensive Traditional Chinese Medicine (TCM) network databases, including TCMSP, TCMID, and ETCM. Furthermore, an analysis of 3 gene expression datasets, sourced from the gene expression omnibus database, facilitated the identification of differential genes associated with KOA. Integrating these findings with data from 5 predominant databases yielded a refined list of KOA-associated targets, which were subsequently aligned with the gene signatures corresponding to AM and LA treatment. Through this alignment, specific molecular targets pertinent to the AM-LA therapeutic axis were elucidated. The construction of a protein-protein interaction network, leveraging the shared genetic markers between KOA pathology and AM-LA intervention, enabled the identification of pivotal molecular targets via the topological analysis facilitated by CytoNCA plugins. Subsequent GO and KEGG enrichment analyses fostered the development of a holistic herbal-ingredient-target network and a core target-signal pathway network. Molecular docking techniques were employed to validate the interaction between 5 central molecular targets and their corresponding active compounds within the AM-LA complex. Our findings suggest that the AM-LA combination modulates key biological processes, including cellular activity, reactive oxygen species modification, metabolic regulation, and the activation of systemic immunity. By either augmenting or attenuating crucial signaling pathways, such as MAPK, calcium, and PI3K/AKT pathways, the AM-LA dyad orchestrates a comprehensive regulatory effect on immune-inflammatory responses, cellular proliferation, differentiation, apoptosis, and antioxidant defenses, offering a novel therapeutic avenue for KOA management. This study, underpinned by gene expression omnibus gene chip analyses and network pharmacology, advances our understanding of the molecular underpinnings governing the inhibitory effects of AM and LA on KOA progression, laying the groundwork for future explorations into the active components and mechanistic pathways of TCM in KOA treatment.

Accelerated Method for Determining Ischemic Brain Damage in Rats and Assessment the Neuroprotective Effect of a Complex Herbal Remedy.

The severity of ischemic injury was evaluated by densitometry of brain samples stained with 2,3,5-triphenyltetrazolium chloride (TTC) on a rat model of cerebral ischemia/reperfusion (common carotid artery occlusion) and the neuroprotective activity of an extract of Astragalus membranaceus, Scutellaria baicalensis, and Phlojodicarpus sibiricus was assessed. Occlusion of the common carotid arteries led to a weakening of TTC staining of the brain tissue: densitometric indicators of the staining intensity for the cortex and striatum were lower than the corresponding indicators of sham-operated rats by 18.3 and 10.4%. The mean intensity of staining of brain samples did not differ in rats treated with the extract and sham-operated animals, which attested to its neuroprotective effect. The applied method is convenient for evaluation of the severity of ischemic brain damage at the early stages and screening potential neuroprotective agents.

Explore the mechanism of Astragalus membranaceus and Poria cocos drug pair in improving immunity based on network pharmacology.

The aim of this study was to investigate the key targets and molecular mechanisms of the drug pair Astragalus membranaceus and Poria cocos (HFDP) in the treatment of immunity. We utilized network pharmacology, molecular docking, and immune infiltration techniques in conjunction with data from the GEO database. Previous clinical studies have shown that HFDP has a positive impact on immune function. We first identified the active ingredients and targets of HFDP from the Traditional Chinese Medicine Systems Pharmacology database and the Swiss Target Prediction database, respectively. Next, we retrieved the differentially expressed genes (DEGs) related to immunity from the GEO databases. The intersection targets of the drugs and diseases were then analyzed using the STRING database for protein-protein interaction (PPI) network analysis, and the core targets were determined through topological analysis. Finally, the intersection genes were further analyzed using the DAVID database for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses. Subsequently, by analyzing the expression and prognostic survival of 12 core targets, 5 core target genes were identified, and molecular docking between the hub genes and immunity was performed. Finally, we used the CIBERSORT algorithm to analyze the immune infiltration of immunity genes In this study, 34 effective ingredients of HFDP, 530 target genes, and 568 differential genes were identified. GO and KEGG analysis showed that the intersection genes of HFDP targets and immunity-related genes were mainly related to complement and coagulation cascades, cytokine receptors, and retinol metabolism pathways. The molecular docking results showed that the 5 core genes had obvious affinity for the active ingredients of HFDP, which could be used as potential targets to improve the immunity of HFDP. Our findings suggest that HFDP is characterized by "multiple components, multiple targets, and multiple pathways" in regulating immunity. It may play an essential role in regulating immunity by regulating the expression and polymorphism of the central target genes ESR1, JUN, CYP3A4, CYP2C9, and SERPINE1.

The protective effect and bioactive compounds of Astragalus membranaceus against neurodegenerative disorders via alleviating oxidative stress in Drosophila.

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.

Herb pair of Huangqi-Danggui exerts anti-tumor immunity to breast cancer by upregulating PIK3R1.

BACKGROUND: According to traditional Chinese medicine (TCM), drugs supplementing the vital energy, Qi, can eliminate tumors by restoring host immunity. The objective of this study is to investigate the underlying immune mechanisms of anti-tumor activity associated with Qi-supplementing herbs, specifically the paired use of Huangqi and Danggui. METHODS: Analysis of compatibility regularity was conducted to screen the combination of Qi-supplementing TCMs. Using the MTT assay and a transplanted tumor mice model, the anti-tumor effects of combination TCMs were investigated in vitro and in vivo. High content analysis and flow cytometry were then used to evaluate cellular immunity, followed by network pharmacology and molecular docking to dissect the significant active compounds and potential mechanisms. Finally, the anti-tumor activity and the mechanism of the active ingredients were verified by molecular experiments. RESULTS: There is an optimal combination of Huangqi and Danggui that, administered as an aqueous extract, can activate immunity to suppress tumor and is more effective than each drug on its own in vitro and in vivo. Based on network pharmacology analysis, PIK3R1 is the core target for the anti-tumor immunity activity of combined Huangqi and Danggui. Molecular docking analysis shows 6 components of the combined Danggui and Huangqi extract (quercetin, jaranol, isorhamnetin, kaempferol, calycosin, and suchilactone) that bind to PIK3R1. Jaranol is the most important component against breast cancer. The suchilactone/jaranol combination and, especially, the suchilactone/kaempferol combination are key for immunity enhancement and the anti-tumor effects of the extract. CONCLUSIONS: The combination of Huangqi and Danggui can activate immunity to suppress breast cancer and is more effective than the individual drugs alone.

A Rapid and Accurate UHPLC Method for Determination of Monosaccharides in Polysaccharides of Different Sources of Radix Astragali and Its Immune Activity Analysis.

With the escalating demand for Astragalus polysaccharides products developed from Radix Astragali (RA), the necessity for quality control of polysaccharides in RA has become increasingly urgent. In this study, a specific method for the simultaneous determination of seven monosaccharides in polysaccharides extracted from Radix Astragali (RA) has been developed and validated using ultra-performance liquid chromatography equipped with an ultraviolet detector (UHPLC-UV) for the first time. The 1-phenyl-3-methyl-5-pyrazolone (PMP) derivatizations were separated on a C18 column (Waters ACQUITYTM, Milfor, MA, USA, 1.8 µm, 2.1 × 100 mm) using gradient elution with a binary system of 5 mm ammonium formate (0.1% formic acid)-acetonitrile for 24 min. Additionally, seven monosaccharides showed good linear relationships (R2, 0.9971-0.9995), adequate precision (RSD < 4.21%), and high recoveries (RSD < 4.70%). The established method was used to analyze 109 batches of RA. Results showed that the Astragalus polysaccharides (APSs) mainly consist of mannose (Man), rhamnose (Rha), glucose (Glu), galactose (Gal), arabinose (Ara), xylose (Xyl); and fucose (Fuc); however, their composition was different among RA samples from different growth patterns, species, growth years, and origins, and the growth mode of RA and the age of wild-simulated RA can be accurately distinguished by principal component analysis (PCA). In addition, the immunological activity of APSs were also evaluated jointly by measurement of the NO release with RAW264.7, with the results showing that APSs have a promoting effect on the release of NO and exhibit a significant correlation with Man, Glu, Xyl, and Fuc contents. Accordingly, the new established monosaccharides analytical method and APS-immune activity determination in this study can provide a reference for quality evaluation and the establishment of quality standards for RA.

Multi-omics approaches for the understanding of therapeutic mechanism for Huang-Qi-Long-Dan Granule against ischemic stroke.

After long-term clinical application, traditional Chinese medicine (TCM) has accumulated rich experience in the stroke treatment. Huang-Qi-Long-Dan Granule (HQLDG) is a TCM formula that has been used in clinical for the treatment of acute ischemic stroke. However, its mechanism against ischemic stroke is still unknown. This study aimed to identify HQLDG's effect against ischemic stroke and explore its underlying mechanism. 16s rRNA sequencing, metabolomics/tryptophan (Trp)-targeted metabolomics analysis and transcriptomic analysis were used to investigate HQLDG underlying therapeutic mechanism. Our results revealed that HQLDG significantly decreased the infarct volume, improved mouse behavior and brain slices pathological staining. In addition, it could ameliorate intestinal barrier damage and regulate tight junction gene expression. 16s rRNA, metabolomics and transcriptomics analysis revealed that HQLDG treatment significantly improved the composition of gut microbiota and Trp metabolism pathway, and further downregulated Th17/IL-17 signaling pathway. HQLDG treatment could significantly decrease serum inflammatory cytokines, IL-17A and IL-22; down-regulate Trp metabolism receptor gene (Ahr), inflammatory cytokines genes (IL-17a, IL-22), and an important coding gene for maintaining the mature Th17 (rorc) in both brain and intestinal tissues. In the contrary, after gut microbiota removal, this effect of HQLDG was impaired. HQLDG treated mouse fecal microbiota transplantation also had positive effect against tMCAO injury. Moreover, AhR inhibitor could decrease IL-17A immunofluorescence. These results suggested that the gut microbiota regulation might be an important intermediate in HQLDG against tMCAO injury. HQLDG might exert anti-ischemic stroke effects through the gut microbiota-Trp metabolism-Th17/IL-17 signaling, which provides new insights into HQLDG-mediated prevention in ischemic stroke.

[Mechanism and compatibility efficacy of Astragali Radix-Chuanxiong Rhizoma drug pair in treating ischemic stroke based on network regulation].

Based on the association network of "drug pair-disease", the effect characteristics of Astragali Radix-Chuanxiong Rhizoma drug pair in the treatment of ischemic stroke(IS) with Qi deficiency and blood stasis and the matching mechanism of the two were explored. Through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction Database, the effective chemical components of the drug pair were screened, and the candidate targets were predicted. Databa-ses such as GeneCards, DrugBank, Online Mendelian Inheritance in Man(OMIM), and Therapeutic Target Database(TTD) were searched to obtain gene targets related to IS. Through STRING and Cytoscape 3.9.1 software, the protein-protein interaction(PPI) network was constructed by using the interaction information of disease syndrome-related genes and candidate targets of drug pairs, and the core targets were screened according to the network topological feature values. Based on the Metascape platform and DAVID database, the biomolecular interaction information was integrated to analyze the Kyoto Encyclopedia of Genes and Genomes(KEGG) and mine biological functions, so as to further explore the mechanism of action and compatibility characteristics of Astragali Radix-Chuan-xiong Rhizoma. The results showed that the candidate biological process was mainly involved in the regulation of functional modules such as immune, blood circulation, neurotransmitter, and oxidative stress, and it was enriched in lipid and atherosclerosis, calcium signaling pathway, and platelet activation. Astragali Radix and Chuanxiong Rhizoma have their own characteristics. Astragali Radix has a regulatory response to growth factors while maintaining the body's immune balance, while Chuanxiong Rhizoma mainly improves the circulatory system and participates in hormone metabolism, so as to indicate the compatibility mechanism of Astragali Radix-Chuanxiong Rhizoma drug pair for multi-target and multi-pathway synergistic treatment of IS. Through further experimental verification, it was found that the Astragali Radix-Chuanxiong Rhizoma drug pair could significantly down-regulate the expression of key targets including TLR4, NF-κB, IL-1ß, F2R, PLCß1, and MYLK. This study preliminarily reveals that the Astragali Radix-Chuanxiong Rhizoma drug pair may play the three replenishing effects of promoting blood circulation, benefiting Qi, and clearing collaterals by correcting immune di-sorders, blood circulation disorders, and inflammation, which provide support for the clinical research on the subsequent improvement of Qi deficiency and blood stasis in the treatment of IS and provide a new idea for the analysis of modern biological connotation of the compatibility of seven emotions of traditional Chinese medicine.

New flavonoid and their anti-A549 cell activity from the bi-directional solid fermentation products of Astragalus membranaceus and Cordyceps kyushuensis.

Astragalus membranaceus and Cordyceps kyushuensis were used to obtain Astragalus membranaceus-Cordyceps kyushuensis bi-directional solid fermentation products using the bi-directional solid fermentation technique. The fermentation products were isolated and purified to obtain 20 individual compounds, of which compound 1 was a novel isoflavane, and compounds 2, 3, and 4 were novel isoflavones, along with 16 known compounds. In vitro experiments demonstrated that compounds 4, 5, 8, 10, and 20 exhibited significant inhibitory activity against A549 lung cancer cells. Specifically, the IC50 value of the novel compound 4 was 53.4 µM, while the IC50 value of cordycepin was 9.0 µM.

Regulatory effects of Astragalus membranaceus polysaccharides on lipid metabolism disorders induced by a high-fat diet in spotted sea bass (Lateolabrax maculatus).

This study evaluated the regulatory effects of Astragalus membranaceus polysaccharides (AMP) on lipid metabolism disorders induced by a high-fat diet (HFD) in spotted sea bass (Lateolabrax maculatus). Compared with the normal diets (10 % lipids), diets containing 15 % lipid levels were used as the high-fat diet (HFD). Three levels of the AMP (0.06 %, 0.08 %, 0.10 %) were added in the HFD and used as experimental diets. A total of 375 spotted sea bass (average weight 3.00 ± 0.01 g) were divided into 15 tanks and deemed as 5 groups, with each tank containing 25 fish. Fish in each group were fed with different diets for 56 days. After feeding, the HFD induced lipid metabolism disorders in fish, as evidenced by elevated serum lipids, malonaldehyde levels, and more severe liver damage. The AMP alleviated the HFD-induced liver damage, as evidenced by the reduced severity of liver histological lesions and malonaldehyde levels. The low-density lipoprotein cholesterol was reduced, and the expression of FAS and PPAR-α were down and up-regulated, respectively. However, the AMP had a limited ability to affect the serum lipids and abdominal fat percentage. These results reveal the potential of the AMP used in aquaculture to regulate lipid metabolism disorders induced by the HFD.

Genome-wide identification and expression pattern analysis of the GRF transcription factor family in Astragalus mongholicus.

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

Integrated phenotypic, transcriptomics and metabolomics: growth status and metabolite accumulation pattern of medicinal materials at different harvest periods of Astragalus Membranaceus Mongholicus.

BACKGROUND: Astragalus membranaceus var. mongholicus (Astragalus), acknowledged as a pivotal "One Root of Medicine and Food", boasts dual applications in both culinary and medicinal domains. The growth and metabolite accumulation of medicinal roots during the harvest period is intricately regulated by a transcriptional regulatory network. One key challenge is to accurately pinpoint the harvest date during the transition from conventional yield content of medicinal materials to high and to identify the core regulators governing such a critical transition. To solve this problem, we performed a correlation analysis of phenotypic, transcriptome, and metabolome dynamics during the harvesting of Astragalus roots. RESULTS: First, our analysis identified stage-specific expression patterns for a significant proportion of the Astragalus root genes and unraveled the chronology of events that happen at the early and later stages of root harvest. Then, the results showed that different root developmental stages can be depicted by co-expressed genes of Astragalus. Moreover, we identified the key components and transcriptional regulation processes that determine root development during harvest. Furthermore, through correlating phenotypes, transcriptomes, and metabolomes at different harvesting periods, period D (Nov.6) was identified as the critical period of yield and flavonoid content increase, which is consistent with morphological and metabolic changes. In particular, we identified a flavonoid biosynthesis metabolite, isoliquiritigenin, as a core regulator of the synthesis of associated secondary metabolites in Astragalus. Further analyses and experiments showed that HMGCR, 4CL, CHS, and SQLE, along with its associated differentially expressed genes, induced conversion of metabolism processes, including the biosynthesis of isoflavones and triterpenoid saponins substances, thus leading to the transition to higher medicinal materials yield and active ingredient content. CONCLUSIONS: The findings of this work will clarify the differences in the biosynthetic mechanism of astragaloside IV and calycosin 7-O-ß-D-glucopyranoside accumulation between the four harvesting periods, which will guide the harvesting and production of Astragalus.

Mechanism of Astragalus membranaceus (Huangqi, HQ) for treatment of heart failure based on network pharmacology and molecular docking.

Heart failure is a leading cause of death in the elderly. Traditional Chinese medicine, a verified alternative therapeutic regimen, has been used to treat heart failure, which is less expensive and has fewer adverse effects. In this study, a total of 15 active ingredients of Astragalus membranaceus (Huangqi, HQ) were obtained; among them, Isorhamnetin, Quercetin, Calycosin, Formononetin, and Kaempferol were found to be linked to heart failure. Ang II significantly enlarged the cell size of cardiomyocytes, which could be partially reduced by Quercetin, Isorhamnetin, Calycosin, Kaempferol, or Formononetin. Ang II significantly up-regulated ANP, BNP, ß-MHC, and CTGF expressions, whereas Quercetin, Isorhamnetin, Calycosin, Kaempferol or Formononetin treatment partially downregulated ANP, BNP, ß-MHC and CTGF expressions. Five active ingredients of HQ attenuated inflammation in Ang II-induced cardiomyocytes by inhibiting the levels of TNF-α, IL-1ß, IL-18 and IL-6. Molecular docking shows Isorhamnetin, Quercetin, Calycosin, Formononetin and Kaempferol can bind with its target protein ESR1 in a good bond by intermolecular force. Quercetin, Calycosin, Kaempferol or Formononetin treatment promoted the expression levels of ESR1 and phosphorylated ESR1 in Ang II-stimulated cardiomyocytes; however, Isorhamnetin treatment had no effect on ESR1 and phosphorylated ESR1 expression levels. In conclusion, our results comprehensively illustrated the bioactives, potential targets, and molecular mechanism of HQ against heart failure. Isorhamnetin, Quercetin, Calycosin, Formononetin and Kaempferol might be the primary active ingredients of HQ, dominating its cardioprotective effects against heart failure through regulating ESR1 expression, which provided a basis for the clinical application of HQ to regulate cardiac hypertrophy and heart failure.

Renal protective effects and mechanisms of Astragalus membranaceus for diabetic kidney disease in animal models: An updated systematic review and meta-analysis.

BACKGROUND: Astragalus membranaceus (AM) shows potential therapeutic benefits for managing diabetic kidney disease (DKD), a leading cause of kidney failure with no cure. However, its comprehensive effects on renal outcomes and plausible mechanisms remain unclear. PURPOSE: This systematic review and meta-analysis aimed to synthesize the effects and mechanisms of AM on renal outcomes in DKD animal models. METHODS: Seven electronic databases were searched for animal studies until September 2023. Risk of bias was assessed based on SYRCLE's Risk of Bias tool. Standardized mean difference (SMD) or mean difference (MD) were estimated for the effects of AM on serum creatinine (SCr), blood urea nitrogen (BUN), albuminuria, histological changes, oxidative stress, inflammation, fibrosis and glucolipids. Effects were pooled using random-effects models. Heterogeneity was presented as I2. Subgroup analysis investigated treatment- and animal-related factors for renal outcomes. Publication bias was assessed using funnel plots and Egger's test. Sensitivity analysis was performed to assess the results' robustness. RevMan 5.3 and Stata MP 15 software were used for statistical analysis. RESULTS: Forty studies involving 1543 animals were identified for analysis. AM treatment significantly decreased SCr (MD = -19.12 µmol/l, 95 % CI: -25.02 to -13.23), BUN (MD = -6.72 mmol/l, 95 % CI: -9.32 to -4.12), urinary albumin excretion rate (SMD = -2.74, 95 % CI: -3.57, -1.90), histological changes (SMD = -2.25, 95 % CI: -3.19 to -1.32). AM treatment significantly improved anti-oxidative stress expression (SMD = 1.69, 95 % CI: 0.97 to 2.41), and decreased inflammation biomarkers (SMD = -3.58, 95 % CI: -5.21 to -1.95). AM treatment also decreased fibrosis markers (i.e. TGF-ß1, CTGF, collagen IV, Wnt4 and ß-catenin) and increased anti-fibrosis marker BMP-7. Blood glucose, lipids and kidney size were also improved compared with the DM control group. CONCLUSION: AM could improve renal outcomes and alleviate injury through multiple signaling pathways. This indicates AM may be an option to consider for the development of future DKD therapeutics.

The Antioxidant Action of Astragali radix: Its Active Components and Molecular Basis.

Astragali radix is a traditional medicinal herb with a long history and wide application. It is frequently used in prescriptions with other medicinal materials to replenish Qi. According to the classics of traditional Chinese medicine, Astragali radix is attributed with properties such as Qi replenishing and surface solidifying, sore healing and muscle generating, and inducing diuresis to reduce edema. Modern pharmacological studies have demonstrated that some extracts and active ingredients in Astragali radix function as antioxidants. The polysaccharides, saponins, and flavonoids in Astragali radix offer beneficial effects in preventing and controlling diseases caused by oxidative stress. However, there is still a lack of comprehensive research on the effective components and molecular mechanisms through which Astragali radix exerts antioxidant activity. In this paper, we review the active components with antioxidant effects in Astragali radix; summarize the content, bioavailability, and antioxidant mechanisms; and offer a reference for the clinical application of Astragalus and the future development of novel antioxidants.

10-Secocycloartane (=9,19-cyclo-9,10-secolanostane) triterpenoid saponins: Huangqiyenins M-X from Astragalus membranaceus (Fisch.) Bge.

Phytochemical investigations of the leaves of Astragalus membranaceus (Fisch.) Bge. have led to the isolation of 12 undescribed triterpenoid saponins named huangqiyenins M-X. The structures of the undescribed compounds were determined using NMR and HRESIMS data. The cytotoxicity of these compounds against the RKO and HT-29 colon cancer cell lines was evaluated. Among these compounds, huangqiyenin W exhibited the highest cytotoxic activity against RKO colon cancer cells, whereas huangqiyenin Q and W showed moderate cytotoxic activity against HT-29 colon cancer cells. The network pharmacology results indicated that STAT3, IL-2 and CXCR1 are the correlated targets of huangqiyenin W against colon cancer, with AGE-RAGE and Th17 cell differentiation as the key signaling pathways.

Formononetin attenuates psoriasiform inflammation by regulating interferon signaling pathway.

BACKGROUND: Psoriasis is a long-lasting, inflammatory, continuous illness caused through T cells and characterized mainly by abnormal growth and division of keratinocytes. Currently, corticosteroids are the preferred option. However, prolonged use of traditional topical medication can lead to adverse reactions and relapse, presenting a significant therapeutic obstacle. Improved alternative treatment options are urgently required. Formononetin (FMN) is a representative component of isoflavones in Huangqi (HQ) [Astragalus membranaceus (Fisch.) Bge.]. It possesses properties that reduce inflammation, combat oxidation, inhibit tumor growth, and mimic estrogen. Although FMN has been shown to ameliorate skin barrier devastation via regulating keratinocyte apoptosis and proliferation, there are no reports of its effectiveness in treating psoriasis. OBJECTIVE: Through transcriptomics clues and experimental investigation, we aimed to elucidate the fundamental mechanisms underlying FMN's action on psoriasis. MATERIALS AND METHODS: Cell viability was examined using CCK8 assay in this study. The results of analysis of differentially expressed genes (DEGs) between FMN-treated HaCaT cells and normal HaCaT cells using RNA-sequencing (RNA-seq) were presented on volcano plots and heatmap. Enrichment analysis was conducted on DEGs using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO), and results were validated through RT-qPCR verification. After 12 days of FMN treatment in psoriasis mouse model, we gauged the PASI score and epidermis thickness. A variety of techniques were used to assess FMN's effectiveness on inhibiting inflammation and proliferation related to psoriasis, including RT-qPCR, HE staining, western blot, and immunohistochemistry (IHC). RESULTS: The findings indicated that FMN could suppress the growth of HaCaT cells using CCK8 assay (with IC50 = 40.64 uM) and 20 uM FMN could reduce the level of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) to the greatest extent. FMN-treated HaCaT cells exhibited 985 up-regulated and 855 down-regulated DEGs compared to normal HaCaT cells. GO analysis revealed that DEGs were linked to interferon (IFN) signaling pathway. Furthermore, FMN improved pathological features, which encompassed decreased erythema, scale, and thickness scores of skin lesions in psoriasis mouse model. In vivo experiments confirmed that FMN down-regulated expression of IFN-α, IFN-ß, IFN-γ, decreased secretion of TNF-α and IL-17 inflammatory factors, inhibited expression of IFN-related chemokines included Cxcl9, Cxcl10, Cxcl11 and Cxcr3 and reduced expression of transcription factors p-STAT1, p-STAT3 and IFN regulatory factor 1 (IRF1) in the imiquimod (IMQ) group. CONCLUSIONS: In summary, these results suggested that FMN played an anti-inflammatory and anti-proliferative role in alleviating psoriasis by inhibiting IFN signaling pathway, and FMN could be used as a potential therapeutic agent.

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.

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.

Dual-channel hypergraph convolutional network for predicting herb-disease associations.

Herbs applicability in disease treatment has been verified through experiences over thousands of years. The understanding of herb-disease associations (HDAs) is yet far from complete due to the complicated mechanism inherent in multi-target and multi-component (MTMC) botanical therapeutics. Most of the existing prediction models fail to incorporate the MTMC mechanism. To overcome this problem, we propose a novel dual-channel hypergraph convolutional network, namely HGHDA, for HDA prediction. Technically, HGHDA first adopts an autoencoder to project components and target protein onto a low-dimensional latent space so as to obtain their embeddings by preserving similarity characteristics in their original feature spaces. To model the high-order relations between herbs and their components, we design a channel in HGHDA to encode a hypergraph that describes the high-order patterns of herb-component relations via hypergraph convolution. The other channel in HGHDA is also established in the same way to model the high-order relations between diseases and target proteins. The embeddings of drugs and diseases are then aggregated through our dual-channel network to obtain the prediction results with a scoring function. To evaluate the performance of HGHDA, a series of extensive experiments have been conducted on two benchmark datasets, and the results demonstrate the superiority of HGHDA over the state-of-the-art algorithms proposed for HDA prediction. Besides, our case study on Chuan Xiong and Astragalus membranaceus is a strong indicator to verify the effectiveness of HGHDA, as seven and eight out of the top 10 diseases predicted by HGHDA for Chuan-Xiong and Astragalus-membranaceus, respectively, have been reported in literature.