Human adipose tissues are an ideal source of stem cells. It is important to find inducers that can safely and effectively differentiate stem cells into functional neurons for clinical use. In this study, we investigat...Human adipose tissues are an ideal source of stem cells. It is important to find inducers that can safely and effectively differentiate stem cells into functional neurons for clinical use. In this study, we investigate the use of Radix Angelicae Sinensis as an inducer of neuronal differentiation. Primary human adipose-derived stem cells were obtained from adult subcutaneous fatty tissue, then pre-induced with 10% Radix Angelicae Sinensis injection for 24 hours, and incubated in serum-free Dulbecco's modified Eagle's medium/Nutrient Mixture F-12 containing 40% Radix Angelicae Sinensis to induce its differentiation into neuron-like cells. Butylated hydroxyanisole, a common in- ducer for neuronal differentiation, was used as the control. After human adipose-derived stem cells differentiated into neuron-like cells under the induction of Radix Angelicae Sinensis for 24 hours, the positive expression of neuron-specific enolase was lower than that of the butylated hydroxyani- sole-induced group, and the expression of glial fibrillary acidic protein was negative. Alter they were induced for 48 hours, the positive expression of neuron specific enolase in human adipose-derived stem cells was significantly higher than that of the butylated hydroxyanisole-induced group. Our experimental findings indicate that Radix Angelicae Sinensis can induce human adipose-derived stem cell differentiation into neuron-like cells and produce less cytotoxicity.展开更多
Objective To investigate the effect of reinforced Decoction of Angelicae Sinensis for enriching blood (RDAEB) on the immunity of immunosuppressed mice induced by cyclophosphamide (Cy). Methods Mice were given RDAEB th...Objective To investigate the effect of reinforced Decoction of Angelicae Sinensis for enriching blood (RDAEB) on the immunity of immunosuppressed mice induced by cyclophosphamide (Cy). Methods Mice were given RDAEB through stomach perfusion for 10 d (50 mg/d). Then, RBC-C3bR rate,RBC-IC rate (as the index- es of erythrocyte immunity)and E-rosette forming rate,acidic a-naphthyl acetate esterase positive rate, lymphocyte transformation rate (as the indexes of cellular immunity) of mice were tested. Results RBC-C3Br rate, RBC-IC rat- e,E-rosette forming rate, acidic α-naphthyl acetate esterase positive rate and lymphocyte transformation rate in the Cy-RDAEB group were markedly higher than those in the Cy group (P<0.0l),and returned to the levels of normal group. Conclusion RDAEB is effective in recovering and enhancing cellular and erythrocyte immunity of immuno- suppressed mice.展开更多
Uniform design was used to optimize extraction condition of direct refluence extraction of coumarins from the Chinese traditional medicine of radix angelicae pubescentis(Duhuo); the sum peak area of coumarins separate...Uniform design was used to optimize extraction condition of direct refluence extraction of coumarins from the Chinese traditional medicine of radix angelicae pubescentis(Duhuo); the sum peak area of coumarins separated with high performance liquid chromatography(HPLC) at detection wavelength of 320nm was considered as detection index, two factors of solvent concentration and extraction time were mainly studied at extraction temperature of 85℃ and a volume ratio of solvent to sample of 10∶1. Optimal subclass, quadric polynomial step by step aggression and neural network method were applied to process the experimental results. The results show that the first and second methods give the same factors combination (concentration of ethanol: 95%, extraction time: 3.6 h) and the second method is much better than the first one. The extraction model is consequently developed.展开更多
Background: Angelicae sinensis radix has been widely applied in traditional Chinese medicine while little isexplored in its potential mechanism. This study aims to elucidate the effective components and defattingmecha...Background: Angelicae sinensis radix has been widely applied in traditional Chinese medicine while little isexplored in its potential mechanism. This study aims to elucidate the effective components and defattingmechanism based on network pharmacology. Methods: Traditional Chinese Medicine Systems PharmacologyDatabase and Analysis Platform was screened to collect the possible active ingredients and their CAS and SMILESwas searched in Pubchem, which further used for reverse molecular docking in Swiss Target Prediction database toobtain potential targets. Hyperlipidemia-related molecules were obtained from GeneCards database, and thepredicted targets of Angelicae sinensis radix for hyperlipidemia treatment were selected by Wayne diagram. Formechanism analysis, the protein-protein interactions were constructed with String, the Gene Oncology enrichmentanalysis and Kyoto Encyclopedia of Genes and Genomes analysis were conducted in DAVID. Results: Usingnetwork-based systems biology analysis, we predicted that 5 active ingredients in Angelicae sinensis radix hasantilipemic effects with 71 potential targets. Through Gene Oncology and Kyoto Encyclopedia of Genes andGenomes analysis, we found that the related signaling pathways mainly involved in arachidonic acid metabolism,and regulation of lipolysis in adipocytes. The related genes are ALOX5, CYP2C19, EPHX2, PTGS1, PTGS2,ADRB1, and ADRB3. Conclusion: Angelicae sinensis radix may alleviate hyperlipidemia through arachidonic acidmetabolism, and regulation of lipolysis in adipocytes. ALOX5, CYP2C19, EPHX2, PTGS1, PTGS2, ADRB1, andADRB3 may be new targets for treatment.展开更多
Background:Traditional Chinese medicine(TCM)has been shown to be effective in treating ischemic stroke(IS),and the combination of Angelicae Sinensis Radix(ASR)and Astragali Radix(AR)is a core TCM prescription that is ...Background:Traditional Chinese medicine(TCM)has been shown to be effective in treating ischemic stroke(IS),and the combination of Angelicae Sinensis Radix(ASR)and Astragali Radix(AR)is a core TCM prescription that is widely acknowledged for its efficacy in IS treatment.This study utilized network pharmacology methods to explore the molecular mechanisms underlying the therapeutic effects of Angelicae Sinensis Radix and Astragali Radix in IS treatment,with preliminary validation conducted through molecular docking.Methods:Information on the structure,targets,main biological functions,and pathways of the active components in Angelicae Sinensis Radix and Astragali Radix was collected using databases such as PubChem,PharmMapper,UniProt,and GeneCards.The results were visualized using software such as Cytoscape 3.6.1,Ledock,and pymol.Results:We retrieved 20 active components and 149 targets associated with the compatibility of Angelicae Sinensis Radix and Astragali Radix from various databases,and GeneCards database was used to search 3350 IS-related gene targets,including 78 key targets of Angelicae Sinensis Radix and Astragali Radix for the treatment of IS.Enrichment analysis of these 78 targets using gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)revealed the involvement of 48 GO terms in the treatment of IS,mainly in biological processes such as metabolism,biological regulation,and stress response.The composition of biological devices such as supercavitary membrane,cell fluid,and extracellular space was also involved.The biological functions mainly included protein binding,ion binding,hydrolytic enzyme activity,and others.The identified pathways were estrogen signaling pathway,mitogen-activated protein kinase(MAPK)signaling pathway,PI3K-AKT signaling pathway,RAP1 signaling pathway,P53 signaling pathway,PPAR signaling pathway,FOXO signaling pathway,RAS signaling pathway,prolactin signaling pathway,HIF-1 signaling pathway,and TNF signaling pathway.Molecular docking analysis showed that the 17 key active components of Angelicae Sinensis Radix and Astragali Radix had strong binding activity with 13 IS key targets.Conclusion:Through the application of network pharmacology methods,it was found that the use of Angelicae Sinensis Radix and Astragali Radix for treating ischemic stroke mainly targets the MAPK and PI3K-AKT signaling pathways,involving several crucial compounds and genes.Nevertheless,additional in vitro and in vivo studies are needed to verify these findings.展开更多
Objective:Using network pharmacology and molecular docking technology to explore the possible mechanism of Huangqi(Astragali radix)-Danggui(Angelicae sinensis radix)on the treatment of spinal cord injury.Methods:The a...Objective:Using network pharmacology and molecular docking technology to explore the possible mechanism of Huangqi(Astragali radix)-Danggui(Angelicae sinensis radix)on the treatment of spinal cord injury.Methods:The active components and the targets related to Astragali radix-Angelicae sinensis radix were screened out on the Traditional Chinese Medicine Systems Pharmacology database.Genes of spinal cord injury were searched by Genecards and the Online Mendelian Inheritance in Man databases.The intersection targets between herbs and diseases were obtained through online Venn diagrams.A components-targets-pathways network was established on Cytoscape 3.8.1 software.The STRING database was used to construct the intersection protein interaction network and screen out core targets.Gene Ontology biological processes and enrichment analysis based on the Kyoto Encyclopedia of Genes and Genes of intersection proteins were performed via DAVID database.Finally,the molecular docking with key components and core targets were performed in AutoDock software.Results:The 22 chemical components including quercetin,kaempferol were collected from Astragali radix-Angelicae sinensis radix.It acts on 110 targets,and interleukin-6,tumor necrosis factor,mitogen-activated protein kinase,tumor antigen p53 were considered as the major targets.50 pathways like Interleukin-17 signaling pathway,tumor necrosis factor signaling pathway and mitogen-activated protein kinase signaling pathway participate in biological processes such as positive transcription regulation and lipopolysacchanide response.The molecular docking revealed that the core targets had stronger binding activity with its corresponding active components.Conclusion:Astragali radix-Angelicae sinensis radix has the characteristics of multi-component,multi-target,and multi-pathway effects in treating spinal cord injury.Its potential mechanism may be related to preventing inflammation,improving microcirculation,inhibiting neuronal apoptosis,protecting damaged nerve cells and promoting nerve repair and regeneration.展开更多
Idiopathic pulmonary fibrosis(IPF)is a chronic,progressive,fibrotic interstitial lung disease.Current treatment options for IPF are limited.Radix Astragali(RA)and Radix Angelicae Sinensis(RAS),according to 5:1 ratio c...Idiopathic pulmonary fibrosis(IPF)is a chronic,progressive,fibrotic interstitial lung disease.Current treatment options for IPF are limited.Radix Astragali(RA)and Radix Angelicae Sinensis(RAS),according to 5:1 ratio composed of Danggui Buxue decoction(DGBXD),which have played an essential role in the treatment of IPF.This article reviewed the experimental research,clinical research,and progress of RA and RAS(DGBXD)treating IPF to provide a deeper scientific basis for the future experimental research and clinical research.展开更多
Angelicae Sinensis Radix(Danggui)and Ligusticum Chuanxiong Rhizoma(Chuan Xiong)herb-pair(DC)have been frequently used in Traditional Chinese medicine(TCM)prescriptions for hundreds of years to prevent vascular disease...Angelicae Sinensis Radix(Danggui)and Ligusticum Chuanxiong Rhizoma(Chuan Xiong)herb-pair(DC)have been frequently used in Traditional Chinese medicine(TCM)prescriptions for hundreds of years to prevent vascular diseases and alleviate pain.However,the mechanism of DC herb-pair in the prevention of liver fibrosis development was still unclear.In the present study,the effects and mechanisms of DC herb-pair on liver fibrosis were examined using network pharmacology and mouse fibrotic model.Based on the network pharmacological analysis of 13 bioactive ingredients found in DC,a total of 46 targets and 71 pathways related to anti-fibrosis effects were obtained,which was associated with mitogen-activated protein kinase(MAPK)signal pathway,hepatic inflammation and fibrotic response.Furthermore,this hypothesis was verified using carbon tetrachloride(CCl_4)-induced fibrosis model.Measurement of liver functional enzyme activities and histopathological examination showed that DC dramatically reduced bile acid levels,inflammatory cell infiltration and collagen deposition caused by CCl_4.The increased expression of liver fibrosis markers,such as collagen 1,fibronectin,α-smooth muscle actin(α-SMA)and transforming growth factor-β(TGF-β),and inflammatory factors,such as chemokine(C-C motif)ligand 2(MCP-1),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)and IL-6 in fibrotic mice were significantly downregulated by DC herb-pair through regulation of extracellular signal-regulated kinase 1/2(ERK1/2)-protein kinase B(AKT)signaling pathways.Collectively,these results suggest that DC prevents the development of liver fibrosis by inhibiting collagen deposition,decreasing inflammatory reactions and bile acid accumulation,which provides insights into the mechanisms of herbpair in improving liver fibrosis.展开更多
The intracellular kinase domains of the epidermal growth factor receptor(EGFR) in some tumor cells are significant targets for drug discovery.We have developed a new EGFR cell membrane chromatography(EGFR/CMC)-online-...The intracellular kinase domains of the epidermal growth factor receptor(EGFR) in some tumor cells are significant targets for drug discovery.We have developed a new EGFR cell membrane chromatography(EGFR/CMC)-online-high performance liquid chromatography/mass spectrometry(HPLC/MS) method for screening anti-EGFR antagonists from medicinal herbs such as Radix Angelicae Pubescentis.In this study,the HEK293 EGFR cells with high expression of EGFR were used to prepare cell membrane stationary phase(CMSP) in the EGFR/CMC model.The retention fractions on the EGFR/CMC model were directly analyzed by combining a 10 port columns switcher with a HPLC/MS system online.As a result,osthole from Radix Angelicae Pubescentis was found to be the active component acting on EGFR like dasatinib as the control drug.There was a good relationship between their inhibiting effects on EGFR secretion and HEK293 EGFR cell growth in vitro.This new EGFR/CMC-online-HPLC/MS method can be applied for screening anti-EGFR antagonists from TCMs,for instance,Radix Angelicae Pubescentis.It will be a useful method for drug discovery with natural medicinal herbs as a leading compound resource.展开更多
Angelicae Pubescentis Radix (APR, Duhuo) is a commonly used traditional Chinese medicine and usually used for the treatments of rheumatic diseases. To assess the chemical composition of APR extract, a sensitive and re...Angelicae Pubescentis Radix (APR, Duhuo) is a commonly used traditional Chinese medicine and usually used for the treatments of rheumatic diseases. To assess the chemical composition of APR extract, a sensitive and reliable UPLC-Q?TOF-MS method was used for qualitative analysis. The separation was achieved on an Agilent SB-Ci8 column (1.8 pm, 2.1 mm><50 mm) with a gradient elution system consisting of acetonitrile and water containing 0.1% formic acid. An electrospray ionization (ESI) was used for mass spectrometer, and the data were collected in the positive ion mode, which was operated in a full-scan mode at m/z 100-800. A total of 49 compounds including 46 coumarins were identified according to the MS and MS/MS data. Among them, two were new compounds, and isoangenomalin, scoparone, 4-methyl-umbelliferyl acetate, suberenol,/raw5-dehydroosthol, and oroselone were first reported in APR.展开更多
Objective: To explore the molecular-level mechanism on the hematopoiesis effect of Angelicae sinensis Radix(ASR) with systems-based interactome analysis. Methods: This systems-based interactome analysis was designed t...Objective: To explore the molecular-level mechanism on the hematopoiesis effect of Angelicae sinensis Radix(ASR) with systems-based interactome analysis. Methods: This systems-based interactome analysis was designed to enforce the workflow of "ASR(herb)→compound→target protein→internal protein actions→ending regulated protein for hematopoiesis". This workflow was deployed with restrictions on regulated proteins expresses in bone marrow and anemia disease and futher validated with experiments. Results: The hematopoiesis mechanism of ASR might be accomplished through regulating pathways of cell proliferation towards hemopoiesis with cross-talking agents of spleen tyrosine kinase(SYK), Janus kinase 2(JAK2), and interleukin-2-inducible T-cell kinase(ITK). The hematopoietic function of ASR was also validated by colonyforming assay performed on mice bone marrow cells. As a result, SYK, JAK2 and ITK were activated. Conclusion: This study provides a new approach to systematically study and predict the therapeutic mechanism for ASR based on interactome analysis towards biological process with experimental validations.展开更多
Angelicae Sinensis Radix(AS)is reproted to exert anti-depression effect(ADE)and nourishing blood effect(NBE)in a rat model of depression.The correlation between the two therapeutic effects and its underlying mechanism...Angelicae Sinensis Radix(AS)is reproted to exert anti-depression effect(ADE)and nourishing blood effect(NBE)in a rat model of depression.The correlation between the two therapeutic effects and its underlying mechanisms deserves further study.The current study is designed to explore the underlying mechanisms of correlation between the ADE and NBE of AS based on hepatic metabonomics,network pharmacology and molecular docking.According to metabolomics analysis,30 metabolites involved in 11 metabolic pathways were identified as the potential metabolites for depression.Furthermore,principal component analysis and correlation analysis showed that glutathione,sphinganine,and ornithine were related to pharmacodynamics indicators including behavioral indicators and hematological indicators,indicating that metabolic pathways such as sphingolipid metabolism were involved in the ADE and NBE of AS.Then,a target-pathway network of depression and blood deficiency syndrome was constructed by network pharmacology analysis,where a total of 107 pathways were collected.Moreover,37 active components obtained from Ultra Performance Liquid Chromatography-Triple-Time of Flight Mass Spectrometer(UPLC-Triple-TOF/MS)in AS extract that passed the filtering criteria were used for network pharmacology,where 46 targets were associated with the ADE and NBE of AS.Pathway enrichment analysis further indicated the involvement of sphingolipid metabolism in the ADE and NBE of AS.Molecular docking analysis indciated that E-ligustilide in AS extract exhibited strong binding activity with target proteins(PIK3CA and PIK3CD)in sphingolipid metabolism.Further analysis by Western blot verified that AS regulated the expression of PIK3CA and PIK3CD on sphingolipid metabolism.Our results demonstrated that sphingolipid metabolic pathway was the core mechanism of the correlation between the ADE and NBE of AS.展开更多
Objective:The objective was to study the potential substance basis and action mechanism of Chuanxiong Rhizoma(CX)and Angelicae Dahuricae Radix(AD)on analgesia through network pharmacology and molecular docking.Materia...Objective:The objective was to study the potential substance basis and action mechanism of Chuanxiong Rhizoma(CX)and Angelicae Dahuricae Radix(AD)on analgesia through network pharmacology and molecular docking.Materials and Methods:The active components and targets of CX and AD and pain-related genes were retrieved through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and GeneCards database.Then,the co-action targets were found,protein–protein interaction network was constructed by the String database.The Cytoscape 3.7.1 was used to construct"CX-AD-active components-pain"network.Further enrichment analysis of Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)was carried out to predict its mechanism of action,the top four active components in the network were docked with the targets.Results:There are 26 compounds,45 targets in the network.Among them,(Z)-ligustilide and beta-sitosterol,respectively,have more potential targets in CX and AD,and prostaglandin-endoperoxide synthase(PTGS2),PTGS1 have more ligands.GO analysis shows that molecular functions of CX and AD mainly performed through the G protein-coupled amine receptor activity,adrenergic receptor activity,and catecholamine binding.KEGG analysis indicates that they could exert analgesic effect on the pathways of regulating neuroactive ligand-receptor interaction,serotonergic synapse,and cGMP-PKG signaling pathway.Molecular docking results show that the active compounds are highly compatible with the structure of the protein receptor,and they interact through the hydrogen bond andπ–πbond between the ligand and the active site residues.Conclusions:Through network pharmacology and molecular docking,this study preliminarily revealed the main active components,targets,and potential regulation network of CX and AD,providing a reference for the subsequent experimental research.展开更多
The aim of this study was to establish an ultra-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry method with positive and negative ion exchange scanning mode for simultaneous q...The aim of this study was to establish an ultra-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry method with positive and negative ion exchange scanning mode for simultaneous quantification of two different skeleton components to reveal the differences among raw and processed Angelicae Pubescentis Radix. The results of methodology showed that each compound had good linearity and recovery rates. And the chemometrics results indicate that there were differences not only in Angelicae Pubescentis Radix samples from different sources but also in raw and processed Angelicae Pubescentis Radix. The results of this study confirm that the method has been successfully applied in simultaneous determination and discovering the difference of two different skeleton components between raw and processed Angelicae Pubescentis Radix for the first time. In short, the method could be an effective tool for detecting the quality of traditional Chinese medicine, and can better reveal the difference between raw and processed Chinese medicine from different sources.展开更多
The present study aimed at exploring different roles of the same compound in different environment, using preparative HPLC, and the significance to investigating bio-active constituents in traditional Chinese medicine...The present study aimed at exploring different roles of the same compound in different environment, using preparative HPLC, and the significance to investigating bio-active constituents in traditional Chinese medicine (TCM) on the basis of holism. In this study, the depletion of target component ferulic acid (FA) by using preparative HPLC followed by antioxidant activity testing was applied to investigate the roles of FA in Angelicae Sinansis Radix (DG), Chuanxiong Rhizoma (CX) and their combination (GX). The antioxidant activity was performed by 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity testing. FA was successfully and exclusively depleted from DG, CX, and GX, respectively. By comparing the effects of the samples, it was found that FA was one of the main antioxidant constituents in DG, CX and GX, and the roles of FA were DG 〉 CX 〉 GX. Furthermore, the effects of FA varied at different doses in these herbs. This study provided a reliable and effective approach to clarifying the contribution of same compound in different TCMs to their bio-activities. The role of a constituent in different TCMs might be different, and a component with the same content might have different effects in different chemical environments. Furthermore, this study also suggested the potential utilization of preparative HPLC in the characterization of the roles of multi-ingredients in TCM.展开更多
Objective:To investigate the mechanism by which Astragalus mongholicus Bunge(AM),and Angelica sinensis Diels(AS)act in interstitial lung disease(ILD)based on computational prediction.Methods:We screened the ingredient...Objective:To investigate the mechanism by which Astragalus mongholicus Bunge(AM),and Angelica sinensis Diels(AS)act in interstitial lung disease(ILD)based on computational prediction.Methods:We screened the ingredients of AM and AS in PubMed,the Web of Science,China National Knowledge Infrastructure(CNKI)Databases,etc.Then obtained the potential effective components.By sharing the same molecular with ILD,we got the possible target genes for ILD treatment and constructed components–targets–disease network with Cytoscape software.The CTD(Comparative Toxicogenomics Database)database was used for GO and KEGG enrichment analysis of these target genes.Results:59 active ingredients that can be druggable were chosen from AM,67 active ingredients were chosen from AS.77 overlapping target genes for AM and ILD and 36 overlapping target genes for AS and ILD were acquired.The hub targets of AM were PTGS2,PTGS1,CDK2,MAOA,ESR1,TOP2A,GSK3B,ESR2,PPARG,NOS2,The hub targets of AS were PTGS2,GABRA1,PTGS1,CHRM1,SLC6A2,ADRA1B,ADRAIA,ADRB2,CHRM3,GABRA2,CHRM2.Quercetin,kaempferol,daidzein,pavilion,7-Hydroxycoumarin,and 5-Hydroxycoumarin were the main active ingredients which have more effective targets.Prediction of the protein-protein interaction network showed PTGS2,GSK3B,PPARG,etc.,were the important predicted targets.The enriched KEGG pathways,including the Immune System,Metabolism of lipids and lipoproteins,Cytokine Signaling in the Immune system,Generic Transcription Pathway,The interleukin pathway,Metabolism of proteins,PI3K-Akt signaling pathway,Metabolic pathways,Innate Immune System,Neuroactive ligand-receptor interaction,Metabolism,GPCR downstream signaling,Amine ligand-binding receptors,Class A/1,Calcium signaling pathway.Molecular docking showed that quercetin,kaempferol,daidzein,pavilion,7-Hydroxycoumarin,5-Hydroxycoumarin had good binding activities with PTGS2 and GSK3B,which mainly mediated PI3K/Akt and other important signaling pathways in the pathogenesis of ILD.Conclusion:The components in AS and AM share some common targets,such as PTGS2.AM and AS may ameliorate ILD through the PI3K-Akt signaling pathway which is mediated by GSK3B.PTGS2,PPARG may also be vital target genes in the treatment of ILD with AM and AS.展开更多
基金financially supported by the Science and Technology Project of Sichuan Province,No.2009JY0128the Health Ministry of Sichuan Province in China,No.20060052
文摘Human adipose tissues are an ideal source of stem cells. It is important to find inducers that can safely and effectively differentiate stem cells into functional neurons for clinical use. In this study, we investigate the use of Radix Angelicae Sinensis as an inducer of neuronal differentiation. Primary human adipose-derived stem cells were obtained from adult subcutaneous fatty tissue, then pre-induced with 10% Radix Angelicae Sinensis injection for 24 hours, and incubated in serum-free Dulbecco's modified Eagle's medium/Nutrient Mixture F-12 containing 40% Radix Angelicae Sinensis to induce its differentiation into neuron-like cells. Butylated hydroxyanisole, a common in- ducer for neuronal differentiation, was used as the control. After human adipose-derived stem cells differentiated into neuron-like cells under the induction of Radix Angelicae Sinensis for 24 hours, the positive expression of neuron-specific enolase was lower than that of the butylated hydroxyani- sole-induced group, and the expression of glial fibrillary acidic protein was negative. Alter they were induced for 48 hours, the positive expression of neuron specific enolase in human adipose-derived stem cells was significantly higher than that of the butylated hydroxyanisole-induced group. Our experimental findings indicate that Radix Angelicae Sinensis can induce human adipose-derived stem cell differentiation into neuron-like cells and produce less cytotoxicity.
文摘Objective To investigate the effect of reinforced Decoction of Angelicae Sinensis for enriching blood (RDAEB) on the immunity of immunosuppressed mice induced by cyclophosphamide (Cy). Methods Mice were given RDAEB through stomach perfusion for 10 d (50 mg/d). Then, RBC-C3bR rate,RBC-IC rate (as the index- es of erythrocyte immunity)and E-rosette forming rate,acidic a-naphthyl acetate esterase positive rate, lymphocyte transformation rate (as the indexes of cellular immunity) of mice were tested. Results RBC-C3Br rate, RBC-IC rat- e,E-rosette forming rate, acidic α-naphthyl acetate esterase positive rate and lymphocyte transformation rate in the Cy-RDAEB group were markedly higher than those in the Cy group (P<0.0l),and returned to the levels of normal group. Conclusion RDAEB is effective in recovering and enhancing cellular and erythrocyte immunity of immuno- suppressed mice.
基金Project(2004714) supported by the Development and Innovation Committee of Hunan Province
文摘Uniform design was used to optimize extraction condition of direct refluence extraction of coumarins from the Chinese traditional medicine of radix angelicae pubescentis(Duhuo); the sum peak area of coumarins separated with high performance liquid chromatography(HPLC) at detection wavelength of 320nm was considered as detection index, two factors of solvent concentration and extraction time were mainly studied at extraction temperature of 85℃ and a volume ratio of solvent to sample of 10∶1. Optimal subclass, quadric polynomial step by step aggression and neural network method were applied to process the experimental results. The results show that the first and second methods give the same factors combination (concentration of ethanol: 95%, extraction time: 3.6 h) and the second method is much better than the first one. The extraction model is consequently developed.
文摘Background: Angelicae sinensis radix has been widely applied in traditional Chinese medicine while little isexplored in its potential mechanism. This study aims to elucidate the effective components and defattingmechanism based on network pharmacology. Methods: Traditional Chinese Medicine Systems PharmacologyDatabase and Analysis Platform was screened to collect the possible active ingredients and their CAS and SMILESwas searched in Pubchem, which further used for reverse molecular docking in Swiss Target Prediction database toobtain potential targets. Hyperlipidemia-related molecules were obtained from GeneCards database, and thepredicted targets of Angelicae sinensis radix for hyperlipidemia treatment were selected by Wayne diagram. Formechanism analysis, the protein-protein interactions were constructed with String, the Gene Oncology enrichmentanalysis and Kyoto Encyclopedia of Genes and Genomes analysis were conducted in DAVID. Results: Usingnetwork-based systems biology analysis, we predicted that 5 active ingredients in Angelicae sinensis radix hasantilipemic effects with 71 potential targets. Through Gene Oncology and Kyoto Encyclopedia of Genes andGenomes analysis, we found that the related signaling pathways mainly involved in arachidonic acid metabolism,and regulation of lipolysis in adipocytes. The related genes are ALOX5, CYP2C19, EPHX2, PTGS1, PTGS2,ADRB1, and ADRB3. Conclusion: Angelicae sinensis radix may alleviate hyperlipidemia through arachidonic acidmetabolism, and regulation of lipolysis in adipocytes. ALOX5, CYP2C19, EPHX2, PTGS1, PTGS2, ADRB1, andADRB3 may be new targets for treatment.
基金funded by the Natural Science Foundation of China(No.81874416)Science,Technology Innovation Team Project of Hunan(No.2020RC4050).
文摘Background:Traditional Chinese medicine(TCM)has been shown to be effective in treating ischemic stroke(IS),and the combination of Angelicae Sinensis Radix(ASR)and Astragali Radix(AR)is a core TCM prescription that is widely acknowledged for its efficacy in IS treatment.This study utilized network pharmacology methods to explore the molecular mechanisms underlying the therapeutic effects of Angelicae Sinensis Radix and Astragali Radix in IS treatment,with preliminary validation conducted through molecular docking.Methods:Information on the structure,targets,main biological functions,and pathways of the active components in Angelicae Sinensis Radix and Astragali Radix was collected using databases such as PubChem,PharmMapper,UniProt,and GeneCards.The results were visualized using software such as Cytoscape 3.6.1,Ledock,and pymol.Results:We retrieved 20 active components and 149 targets associated with the compatibility of Angelicae Sinensis Radix and Astragali Radix from various databases,and GeneCards database was used to search 3350 IS-related gene targets,including 78 key targets of Angelicae Sinensis Radix and Astragali Radix for the treatment of IS.Enrichment analysis of these 78 targets using gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)revealed the involvement of 48 GO terms in the treatment of IS,mainly in biological processes such as metabolism,biological regulation,and stress response.The composition of biological devices such as supercavitary membrane,cell fluid,and extracellular space was also involved.The biological functions mainly included protein binding,ion binding,hydrolytic enzyme activity,and others.The identified pathways were estrogen signaling pathway,mitogen-activated protein kinase(MAPK)signaling pathway,PI3K-AKT signaling pathway,RAP1 signaling pathway,P53 signaling pathway,PPAR signaling pathway,FOXO signaling pathway,RAS signaling pathway,prolactin signaling pathway,HIF-1 signaling pathway,and TNF signaling pathway.Molecular docking analysis showed that the 17 key active components of Angelicae Sinensis Radix and Astragali Radix had strong binding activity with 13 IS key targets.Conclusion:Through the application of network pharmacology methods,it was found that the use of Angelicae Sinensis Radix and Astragali Radix for treating ischemic stroke mainly targets the MAPK and PI3K-AKT signaling pathways,involving several crucial compounds and genes.Nevertheless,additional in vitro and in vivo studies are needed to verify these findings.
基金This study was supported by the Traditional Chinese Medicine Research Project of Hubei Provincial Health Commission No.ZY 2021F016Hubei University of Chinese Medicine's“Young Miao Program”project in 2019 No.2019ZZX032.
文摘Objective:Using network pharmacology and molecular docking technology to explore the possible mechanism of Huangqi(Astragali radix)-Danggui(Angelicae sinensis radix)on the treatment of spinal cord injury.Methods:The active components and the targets related to Astragali radix-Angelicae sinensis radix were screened out on the Traditional Chinese Medicine Systems Pharmacology database.Genes of spinal cord injury were searched by Genecards and the Online Mendelian Inheritance in Man databases.The intersection targets between herbs and diseases were obtained through online Venn diagrams.A components-targets-pathways network was established on Cytoscape 3.8.1 software.The STRING database was used to construct the intersection protein interaction network and screen out core targets.Gene Ontology biological processes and enrichment analysis based on the Kyoto Encyclopedia of Genes and Genes of intersection proteins were performed via DAVID database.Finally,the molecular docking with key components and core targets were performed in AutoDock software.Results:The 22 chemical components including quercetin,kaempferol were collected from Astragali radix-Angelicae sinensis radix.It acts on 110 targets,and interleukin-6,tumor necrosis factor,mitogen-activated protein kinase,tumor antigen p53 were considered as the major targets.50 pathways like Interleukin-17 signaling pathway,tumor necrosis factor signaling pathway and mitogen-activated protein kinase signaling pathway participate in biological processes such as positive transcription regulation and lipopolysacchanide response.The molecular docking revealed that the core targets had stronger binding activity with its corresponding active components.Conclusion:Astragali radix-Angelicae sinensis radix has the characteristics of multi-component,multi-target,and multi-pathway effects in treating spinal cord injury.Its potential mechanism may be related to preventing inflammation,improving microcirculation,inhibiting neuronal apoptosis,protecting damaged nerve cells and promoting nerve repair and regeneration.
基金Jiangyin Hospital of Traditional Chinese Medicine(202014 to YF Zhang)Grants from the Wuxi Health Commission’s Scientific Research Project(M202154 to YF Zhang)。
文摘Idiopathic pulmonary fibrosis(IPF)is a chronic,progressive,fibrotic interstitial lung disease.Current treatment options for IPF are limited.Radix Astragali(RA)and Radix Angelicae Sinensis(RAS),according to 5:1 ratio composed of Danggui Buxue decoction(DGBXD),which have played an essential role in the treatment of IPF.This article reviewed the experimental research,clinical research,and progress of RA and RAS(DGBXD)treating IPF to provide a deeper scientific basis for the future experimental research and clinical research.
基金the National Natural Science Foundation of China(No.82004045)the Beijing Nova Program of Science and Technology(No.Z191100001119088)the Beijing University of Chinese Medicine Specific Grant for“Double Top Construction”(No.1000041510168)。
文摘Angelicae Sinensis Radix(Danggui)and Ligusticum Chuanxiong Rhizoma(Chuan Xiong)herb-pair(DC)have been frequently used in Traditional Chinese medicine(TCM)prescriptions for hundreds of years to prevent vascular diseases and alleviate pain.However,the mechanism of DC herb-pair in the prevention of liver fibrosis development was still unclear.In the present study,the effects and mechanisms of DC herb-pair on liver fibrosis were examined using network pharmacology and mouse fibrotic model.Based on the network pharmacological analysis of 13 bioactive ingredients found in DC,a total of 46 targets and 71 pathways related to anti-fibrosis effects were obtained,which was associated with mitogen-activated protein kinase(MAPK)signal pathway,hepatic inflammation and fibrotic response.Furthermore,this hypothesis was verified using carbon tetrachloride(CCl_4)-induced fibrosis model.Measurement of liver functional enzyme activities and histopathological examination showed that DC dramatically reduced bile acid levels,inflammatory cell infiltration and collagen deposition caused by CCl_4.The increased expression of liver fibrosis markers,such as collagen 1,fibronectin,α-smooth muscle actin(α-SMA)and transforming growth factor-β(TGF-β),and inflammatory factors,such as chemokine(C-C motif)ligand 2(MCP-1),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)and IL-6 in fibrotic mice were significantly downregulated by DC herb-pair through regulation of extracellular signal-regulated kinase 1/2(ERK1/2)-protein kinase B(AKT)signaling pathways.Collectively,these results suggest that DC prevents the development of liver fibrosis by inhibiting collagen deposition,decreasing inflammatory reactions and bile acid accumulation,which provides insights into the mechanisms of herbpair in improving liver fibrosis.
基金supported by the National Natural Science Foundation of China (30730110)Program for New Century Excellent Talents in University (NCET-08-0437)
文摘The intracellular kinase domains of the epidermal growth factor receptor(EGFR) in some tumor cells are significant targets for drug discovery.We have developed a new EGFR cell membrane chromatography(EGFR/CMC)-online-high performance liquid chromatography/mass spectrometry(HPLC/MS) method for screening anti-EGFR antagonists from medicinal herbs such as Radix Angelicae Pubescentis.In this study,the HEK293 EGFR cells with high expression of EGFR were used to prepare cell membrane stationary phase(CMSP) in the EGFR/CMC model.The retention fractions on the EGFR/CMC model were directly analyzed by combining a 10 port columns switcher with a HPLC/MS system online.As a result,osthole from Radix Angelicae Pubescentis was found to be the active component acting on EGFR like dasatinib as the control drug.There was a good relationship between their inhibiting effects on EGFR secretion and HEK293 EGFR cell growth in vitro.This new EGFR/CMC-online-HPLC/MS method can be applied for screening anti-EGFR antagonists from TCMs,for instance,Radix Angelicae Pubescentis.It will be a useful method for drug discovery with natural medicinal herbs as a leading compound resource.
基金National Nature Science Foundation of China(Grant Nos.81503208,81403068,30672609)Beijing Municipal Natural Science Foundation(Grant No.7144219)National Key Technology R&D Program of China(Grant No.2011BAI07B08)
文摘Angelicae Pubescentis Radix (APR, Duhuo) is a commonly used traditional Chinese medicine and usually used for the treatments of rheumatic diseases. To assess the chemical composition of APR extract, a sensitive and reliable UPLC-Q?TOF-MS method was used for qualitative analysis. The separation was achieved on an Agilent SB-Ci8 column (1.8 pm, 2.1 mm><50 mm) with a gradient elution system consisting of acetonitrile and water containing 0.1% formic acid. An electrospray ionization (ESI) was used for mass spectrometer, and the data were collected in the positive ion mode, which was operated in a full-scan mode at m/z 100-800. A total of 49 compounds including 46 coumarins were identified according to the MS and MS/MS data. Among them, two were new compounds, and isoangenomalin, scoparone, 4-methyl-umbelliferyl acetate, suberenol,/raw5-dehydroosthol, and oroselone were first reported in APR.
文摘Objective: To explore the molecular-level mechanism on the hematopoiesis effect of Angelicae sinensis Radix(ASR) with systems-based interactome analysis. Methods: This systems-based interactome analysis was designed to enforce the workflow of "ASR(herb)→compound→target protein→internal protein actions→ending regulated protein for hematopoiesis". This workflow was deployed with restrictions on regulated proteins expresses in bone marrow and anemia disease and futher validated with experiments. Results: The hematopoiesis mechanism of ASR might be accomplished through regulating pathways of cell proliferation towards hemopoiesis with cross-talking agents of spleen tyrosine kinase(SYK), Janus kinase 2(JAK2), and interleukin-2-inducible T-cell kinase(ITK). The hematopoietic function of ASR was also validated by colonyforming assay performed on mice bone marrow cells. As a result, SYK, JAK2 and ITK were activated. Conclusion: This study provides a new approach to systematically study and predict the therapeutic mechanism for ASR based on interactome analysis towards biological process with experimental validations.
基金the National Nature Science Foundation of China(No.82004502)the Youth Science and Technology Research Fund of Shanxi Province(No.201901D211138)+1 种基金the National S&T Major Projects for“Major New Drugs Innovation and Development”(No.2017ZX09301047)the Key R&D Project of Shanxi Province(No.202102130501010).
文摘Angelicae Sinensis Radix(AS)is reproted to exert anti-depression effect(ADE)and nourishing blood effect(NBE)in a rat model of depression.The correlation between the two therapeutic effects and its underlying mechanisms deserves further study.The current study is designed to explore the underlying mechanisms of correlation between the ADE and NBE of AS based on hepatic metabonomics,network pharmacology and molecular docking.According to metabolomics analysis,30 metabolites involved in 11 metabolic pathways were identified as the potential metabolites for depression.Furthermore,principal component analysis and correlation analysis showed that glutathione,sphinganine,and ornithine were related to pharmacodynamics indicators including behavioral indicators and hematological indicators,indicating that metabolic pathways such as sphingolipid metabolism were involved in the ADE and NBE of AS.Then,a target-pathway network of depression and blood deficiency syndrome was constructed by network pharmacology analysis,where a total of 107 pathways were collected.Moreover,37 active components obtained from Ultra Performance Liquid Chromatography-Triple-Time of Flight Mass Spectrometer(UPLC-Triple-TOF/MS)in AS extract that passed the filtering criteria were used for network pharmacology,where 46 targets were associated with the ADE and NBE of AS.Pathway enrichment analysis further indicated the involvement of sphingolipid metabolism in the ADE and NBE of AS.Molecular docking analysis indciated that E-ligustilide in AS extract exhibited strong binding activity with target proteins(PIK3CA and PIK3CD)in sphingolipid metabolism.Further analysis by Western blot verified that AS regulated the expression of PIK3CA and PIK3CD on sphingolipid metabolism.Our results demonstrated that sphingolipid metabolic pathway was the core mechanism of the correlation between the ADE and NBE of AS.
基金financially supported by NSFC-DFG(No.81861138042)Natural Science Foundation of China(No.81673634)+1 种基金Natural Science Foundation of Shandong,China(No.ZR2019MC004)the high-end talent team construction foundation(No.108-10000318)
文摘Objective:The objective was to study the potential substance basis and action mechanism of Chuanxiong Rhizoma(CX)and Angelicae Dahuricae Radix(AD)on analgesia through network pharmacology and molecular docking.Materials and Methods:The active components and targets of CX and AD and pain-related genes were retrieved through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and GeneCards database.Then,the co-action targets were found,protein–protein interaction network was constructed by the String database.The Cytoscape 3.7.1 was used to construct"CX-AD-active components-pain"network.Further enrichment analysis of Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)was carried out to predict its mechanism of action,the top four active components in the network were docked with the targets.Results:There are 26 compounds,45 targets in the network.Among them,(Z)-ligustilide and beta-sitosterol,respectively,have more potential targets in CX and AD,and prostaglandin-endoperoxide synthase(PTGS2),PTGS1 have more ligands.GO analysis shows that molecular functions of CX and AD mainly performed through the G protein-coupled amine receptor activity,adrenergic receptor activity,and catecholamine binding.KEGG analysis indicates that they could exert analgesic effect on the pathways of regulating neuroactive ligand-receptor interaction,serotonergic synapse,and cGMP-PKG signaling pathway.Molecular docking results show that the active compounds are highly compatible with the structure of the protein receptor,and they interact through the hydrogen bond andπ–πbond between the ligand and the active site residues.Conclusions:Through network pharmacology and molecular docking,this study preliminarily revealed the main active components,targets,and potential regulation network of CX and AD,providing a reference for the subsequent experimental research.
文摘The aim of this study was to establish an ultra-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry method with positive and negative ion exchange scanning mode for simultaneous quantification of two different skeleton components to reveal the differences among raw and processed Angelicae Pubescentis Radix. The results of methodology showed that each compound had good linearity and recovery rates. And the chemometrics results indicate that there were differences not only in Angelicae Pubescentis Radix samples from different sources but also in raw and processed Angelicae Pubescentis Radix. The results of this study confirm that the method has been successfully applied in simultaneous determination and discovering the difference of two different skeleton components between raw and processed Angelicae Pubescentis Radix for the first time. In short, the method could be an effective tool for detecting the quality of traditional Chinese medicine, and can better reveal the difference between raw and processed Chinese medicine from different sources.
基金supported by National Key Technology R&D Program(No.2008BAI51B01)the Specialized Research Fund for the Doctoral Program of Higher Education of China(No.20113237110010)A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)
文摘The present study aimed at exploring different roles of the same compound in different environment, using preparative HPLC, and the significance to investigating bio-active constituents in traditional Chinese medicine (TCM) on the basis of holism. In this study, the depletion of target component ferulic acid (FA) by using preparative HPLC followed by antioxidant activity testing was applied to investigate the roles of FA in Angelicae Sinansis Radix (DG), Chuanxiong Rhizoma (CX) and their combination (GX). The antioxidant activity was performed by 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity testing. FA was successfully and exclusively depleted from DG, CX, and GX, respectively. By comparing the effects of the samples, it was found that FA was one of the main antioxidant constituents in DG, CX and GX, and the roles of FA were DG 〉 CX 〉 GX. Furthermore, the effects of FA varied at different doses in these herbs. This study provided a reliable and effective approach to clarifying the contribution of same compound in different TCMs to their bio-activities. The role of a constituent in different TCMs might be different, and a component with the same content might have different effects in different chemical environments. Furthermore, this study also suggested the potential utilization of preparative HPLC in the characterization of the roles of multi-ingredients in TCM.
基金National Natural Science Foundation of China(81903934) Tianjin Health Science and Technology Project(ZC20205).
文摘Objective:To investigate the mechanism by which Astragalus mongholicus Bunge(AM),and Angelica sinensis Diels(AS)act in interstitial lung disease(ILD)based on computational prediction.Methods:We screened the ingredients of AM and AS in PubMed,the Web of Science,China National Knowledge Infrastructure(CNKI)Databases,etc.Then obtained the potential effective components.By sharing the same molecular with ILD,we got the possible target genes for ILD treatment and constructed components–targets–disease network with Cytoscape software.The CTD(Comparative Toxicogenomics Database)database was used for GO and KEGG enrichment analysis of these target genes.Results:59 active ingredients that can be druggable were chosen from AM,67 active ingredients were chosen from AS.77 overlapping target genes for AM and ILD and 36 overlapping target genes for AS and ILD were acquired.The hub targets of AM were PTGS2,PTGS1,CDK2,MAOA,ESR1,TOP2A,GSK3B,ESR2,PPARG,NOS2,The hub targets of AS were PTGS2,GABRA1,PTGS1,CHRM1,SLC6A2,ADRA1B,ADRAIA,ADRB2,CHRM3,GABRA2,CHRM2.Quercetin,kaempferol,daidzein,pavilion,7-Hydroxycoumarin,and 5-Hydroxycoumarin were the main active ingredients which have more effective targets.Prediction of the protein-protein interaction network showed PTGS2,GSK3B,PPARG,etc.,were the important predicted targets.The enriched KEGG pathways,including the Immune System,Metabolism of lipids and lipoproteins,Cytokine Signaling in the Immune system,Generic Transcription Pathway,The interleukin pathway,Metabolism of proteins,PI3K-Akt signaling pathway,Metabolic pathways,Innate Immune System,Neuroactive ligand-receptor interaction,Metabolism,GPCR downstream signaling,Amine ligand-binding receptors,Class A/1,Calcium signaling pathway.Molecular docking showed that quercetin,kaempferol,daidzein,pavilion,7-Hydroxycoumarin,5-Hydroxycoumarin had good binding activities with PTGS2 and GSK3B,which mainly mediated PI3K/Akt and other important signaling pathways in the pathogenesis of ILD.Conclusion:The components in AS and AM share some common targets,such as PTGS2.AM and AS may ameliorate ILD through the PI3K-Akt signaling pathway which is mediated by GSK3B.PTGS2,PPARG may also be vital target genes in the treatment of ILD with AM and AS.