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A Network Pharmacology Analysis to Explore the Effect of Astragali Radix-Radix Angelica Sinensis on Traumatic Brain Injury.

ABSTRACT: Traumatic brain injury (TBI) is a critical public health and socioeconomic problem worldwide. The herb pair Astragali Radix (AR)-Radix Angelica Sinensis (RAS) is a common prescribed herbal formula or is added to other Chinese medicine prescriptions for traumatic brain injury (TBI) treatment. However, the underlying mechanisms are unclear. In this study, we aimed to explore the active ingredients and action targets of AR-RAS based on the combined methods of network pharmacology prediction and experimental verification. Furthermore, the corresponding potential mechanisms of "multicomponents, multitargets, and multipathways" were disclosed. Methods. A network pharmacology approach including ADME (absorption, distribution, metabolism, and excretion) filter analysis, target prediction, known therapeutic targets collection, Gene Ontology (GO), pathway enrichment analysis, and network construction was used in this study. Further verification experiments were performed to reveal the therapeutic effects of AR-RAS in a rat model of TBI. Results. The comprehensive systematic approach was to successfully identify 14 bioactive ingredients in AR-RAS, while 33 potential targets hit by these ingredients related to TBI. Based on GO annotation analysis, multiple biological processes were significantly regulated by AR-RAS. In addition, 89 novel signaling pathways (P<0.05) underlying the effects of AR-RAS for TBI treatment were identified by DAVID. The neurotrophin signaling pathway was suggested as the major related pathway targeted by AR-RAS to improve axonal growth. The animal experiment confirmed that AR-RAS significantly induced tissue recovery and improved neurological deficits on the 14th day (P<0.01). Treatment with AR-RAS markedly reduced the protein and mRNA expression level of NogoA in the hippocampus of TBI rats. Conclusion. Our work illuminates the "multicompounds, multitargets, and multipathways" curative action of AR-RAS in the treatment of TBI by network pharmacology. The animal experiment verifies the effects of AR-RAS on neurological function improvement and axonal outgrowth via downregulation of NogoA expression, providing a theoretical basis for further research on treatment of TBI.

SUBMITTER: Xie G

PROVIDER: S-EPMC6286735 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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A Network Pharmacology Analysis to Explore the Effect of Astragali Radix-Radix Angelica Sinensis on Traumatic Brain Injury.

Xie Genggeng G Peng Weijun W Li Pengfei P Xia Zian Z Zhong Yuanyuan Y He Feng F Tulake Yimingaji Y Feng Dandan D Wang Yang Y Xing Zhihua Z

BioMed research international 20181125

Traumatic brain injury (TBI) is a critical public health and socioeconomic problem worldwide. The herb pair Astragali Radix (AR)-Radix Angelica Sinensis (RAS) is a common prescribed herbal formula or is added to other Chinese medicine prescriptions for traumatic brain injury (TBI) treatment. However, the underlying mechanisms are unclear. In this study, we aimed to explore the active ingredients and action targets of AR-RAS based on the combined methods of network pharmacology pred ...[more]

PMID: 30596090

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Project description:Astragali Radix (AR) has been widely used in traditional Chinese medicine prescriptions for acute and chronic liver injury. However, little is known about the effects of AR on acetaminophen (APAP)-induced liver injury (ALI). In the current study, a network pharmacology–based approach was applied to characterize the action mechanism of AR on ALI. All compounds of AR were obtained from the corresponding databases, and active compounds were selected according to its oral bioavailability and drug-likeness index. The potential genes of AR were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) and PubChem, whereas the potential genes related to ALI were obtained from Online databases (GeneCards and Online Mendelian Inheritance in Man) and Gene Expression Omnibus profiles. The enriched processes, pathways, and target genes of the diseases were analyzed by referring to the Search Tool for the Retrieval of Interacting Genes/Proteins database. A network constructed through Cytoscape software was used to identify the target proteins that connected the compounds in AR with the differential genes of ALI. Subsequently, the potential underlying action mechanisms of AR on ALI predicted by the network pharmacology analyses were experimentally validated in APAP-induced liver injury in mice and HL7702 cells incubated with APAP. The compound-target network included 181 targets, whereas the potential genes related to ALI were 4,621. A total of 49 AR–ALI crossover proteins, corresponding to 49 genes, were filtered into a protein–protein interaction network complex and designated as the potential targets of AR on ALI. Among the genes, the three highest-scoring genes, MYC, MAPK8, and CXCL8 were highly associated with apoptosis in ALI. Then in vitro and in vivo experiments confirmed that AR exhibited its prominent therapeutic effects on ALI mainly via regulating hepatocyte apoptosis related to inhibiting the expressions of MYC (c-Myc), MAPK8 (JNK1), and CXCL8 (IL-8). In conclusion, our study suggested that the combination of network pharmacology prediction with experimental validation might offer a useful tool to characterize the molecular mechanism of AR on ALI.

Project description:According to current research, the primary active ingredients of Radix Astragali (RA), such as saponins, flavonoids, and polysaccharides, play an important role in anti-inflammatory effects. However, the exact molecular mechanism underlying the action was not elucidated to date. Our research attempted to determine the active components in RA and to investigate the interaction between the active components and targets involved in the anti-inflammation activity by network pharmacology and molecular docking. The active components and targets of RA were screened out by TCMSP. Thereafter, through the "anti-inflammation effect" and "inflammation" as the keywords, disease targets were obtained from the GeneCards database. The PPI network was constructed with Cytoscape 3.8.0 software to screen core targets. The GO function and KEGG analysis were enriched and analyzed through the Metascape platform, obtaining the 3-dimensional view of the core targets from the PDB database, and then, performing molecular docking in AutoDock Vina, a heatmap was constructed using the binding free energies in GraphPad Prism 8. The Discovery Studio software was used for docking analysis, and eventually, the docking results were visualized. We also explored the targets and signaling pathways of Astragaloside IV acting on anti-inflammatory effects via constructing compound-disease-target-pathway network. 18 active components and 45 targets of RA were screened out. The main anti-inflammatory active components of RA were quercetin, Astragaloside IV, kaempferol, 7-O-methylisomucronulatol, and formononetin, and the strongly interacting core proteins were TNF, IL6, IL1B, TLR4, CXCL8, CCL2, IL10, VEGFA, and MMP9. The signal pathways mainly involved include Lipid and atherosclerosis, IL-17 signaling pathway, Chagas disease, leishmaniasis, and TNF signaling pathway. Moreover, molecular docking showed that the 2 most active compounds, Astragaloside IV and kaempferol, could efficiently bind with the targets TNF, TLR4, and IL10. Astragaloside IV may play a part in anti-inflammatory effects through pathways such as HIF-1 signaling pathway, Inflammatory bowel disease and Hepatitis B ect. RA exhibits the characteristic of multicomponent and multitarget synergistic effects in exerting anti-inflammatory effects and the effective component of RA is Astragaloside IV, targeting TNF, TLR4, and IL10.

Project description:BackgroundPolygoni Cuspidati Rhizoma et Radix (PCRR), a well-known traditional Chinese medicine (TCM), inhibits inflammation associated with various human diseases. However, the anti-inflammatory effects of PCRR in acute lung injury (ALI) and the underlying mechanisms of action remain unclear.AimTo determine the ingredients related to PCRR for treatment of ALI using multiple databases to obtain potential targets for fishing.MethodsRecognized and candidate active compounds for PCRR were obtained from Traditional Chinese Medicine Systems Pharmacology, STITCH, and PubMed databases. Target ALI databases were built using the Therapeutic Target, DrugBank, DisGeNET, Online Mendelian Inheritance in Man, and Genetic Association databases. Network pharmacology includes network construction, target prediction, topological feature analysis, and enrichment analysis. Bioinformatics resources from the Database for Annotation, Visualization and Integrated Discovery were utilized for gene ontology biological process and Kyoto Encyclopedia of Genes and Genomes network pathway enrichment analysis, and molecular docking techniques were adopted to verify the combination of major active ingredients and core targets.ResultsThirteen bioactive compounds corresponding to the 433 PCRR targets were identified. In addition, 128 genes were closely associated with ALI, 60 of which overlapped with PCRR targets and were considered therapeutically relevant. Functional enrichment analysis suggested that PCRR exerted its pharmacological effects in ALI by modulating multiple pathways, including the cell cycle, cell apoptosis, drug metabolism, inflammation, and immune modulation. Molecular docking results revealed a strong associative relationship between the active ingredient and core target.ConclusionPCRR alleviates ALI symptoms via molecular mechanisms predicted by network pharmacology. This study proposes a strategy to elucidate the mechanisms of TCM at the network pharmacology level.

Project description:BackgroundAstragalus membranaceus (Huang-qi, AM) and Angelica sinensis (Dang-gui, AS) are common Chinese herbal medicines and have historically been used in spinal cord injury (SCI) therapies. However, the underlying molecular mechanisms of AM&AS remain little understood. The purpose of this research was to explore the bioactive components and the mechanisms of AM&AS in treating SCI according to network pharmacology and the molecular docking approach.MethodsAM&AS active ingredients were first searched from Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Traditional Chinese Medicine Information Database (TCM-ID). Meanwhile, we collected relevant target genes of SCI through the GeneCards database, OMIM database, PharmGkb database, DurgBank database, and TDD database. By utilizing the STRING database, we constructed a network of protein-protein interactions (PPIs). In addition, we used R and STRING to perform GO and KEGG function enrichment analyses. Subsequently, AutoDock Vina was employed for a molecular docking study on the most active ingredients and most targeted molecules to validate the results of the network pharmacology analysis mentioned above.ResultThe overall number of AM&AS active compounds identified was 22, while the number of SCI-related targets identified was 159. Then, the 4 key active ingredients were MOL000098 quercetin, MOL000422 kaempferol, MOL000354 isorhamnetin, and MOL000392 formononetin. A total of fourteen core targets were TP53, ESR1, MAPK1, MTC, HIF1A, HSP90AA1, FOS, MAPK14, STAT1, AKT1, EGFR, RELA, CCND1, and RB1. The KEGG enrichment analysis results indicated that lipid and atherosclerosis, PI3K-Akt signaling pathway, human cytomegalovirus infection, fluid shear stress, and atherosclerosis, etc., were enhanced with SCI development. Based on the analyses of docked molecules, four main active compounds had high affinity for the key targets.ConclusionsAltogether, it identified the mechanisms by which AM&AS was used for SCI treatment, namely, active ingredients, targets and signaling pathways. Consequently, further research into AM&AS treating SCI can be conducted on this scientific basis.

Project description:BackgroundAstragali Radix-Curcumae Rhizoma (ARCR), a classic drug pair, has been widely used for the treatment of gastric intraepithelial neoplasia (GIN) in China. However, the underlying mechanisms of this drug pair are still unknown. Thus, elucidating the molecular mechanism of ARCR for treating GIN is imperative.MethodsThe active components and targets of ARCR were determined from the TCMSP database, and the differentially expressed genes related to GIN were identified from the GSE130823 dataset. The protein-protein interaction (PPI) network and ARCR-active component-target-pathway network were constructed by STRING 11.0 and Cytoscape 3.7.2, respectively. In addition, a receiver operating characteristic curve (ROC) was conducted to verify the key targets, and enrichment analyses were performed using R software. Molecular docking was carried out to test the binding capacity between core active components and key targets.Results31 active components were obtained from ARCR, among which 22 were hit by the 51 targets associated with GIN. Gene Ontology (GO) functional enrichment analysis showed that biological process (BP), molecular function (MF), and cellular component (CC) were most significantly enriched in response to a drug, catecholamine binding, and apical part of the cell, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated ARCR against GIN through regulation of neuroactive ligand-receptor interaction, nitrogen metabolism, calcium signaling pathway, chemical carcinogenesis-receptor activation, drug metabolism, gap junction, and cancers. In the PPI network, 15 potential targets were identified, of which nine key targets were proven to have higher diagnostic values in ROC. Molecular docking revealed a good binding affinity of active components (quercetin, bisdemethoxycurcumin, and kaempferol) with the corresponding targets (CYP3A4, CYP1A1, HMOX1, DRD2, DPP4, ADRA2A, ADRA2C, NR1I2, and LGALS4).ConclusionThis study revealed the active components and molecular mechanism by which ARCR treatment is effective against GIN through regulating multipathway, such as neuroactive ligand-receptor interaction, nitrogen metabolism, and calcium signaling pathway.

Project description:Background:Astragali Radix (AR) is widely-used for improving liver fibrosis, but, the mechanism of action has not been systematically explained. This study aims to investigate the mechanism of AR intervention in liver fibrosis based on comprehensive metabolomics combined with network pharmacology approach. Materials and methods:UPLC-Q-TOF/MS based metabolomics technique was used to explore the specific metabolites and possible pathways of AR affecting the pathological process of liver fibrosis. Network pharmacology analysis was introduced to explore the key targets of AR regarding the mechanisms on liver fibrosis. Results:AR significantly reduced the levels of ALT, AST and AKP in serum, and improved pathological characteristics. Metabolomics analysis showed that the therapeutic effect of AR was mainly related to the regulation of nine metabolites, including sphingosine, 6-keto-prostaglandin F1a, LysoPC (O-18:0), 3-dehydrosphinganine, 5,6-epoxy-8,11,14-eicosatrienoic acid, leukotriene C4, taurochenodesoxycholic acid, LysoPC (18:1 (9Z)) and 2-acetyl-1-alkyl-sn-glycero-3-phosphocholine. Pathway analysis indicated that the treatment of AR on liver fibrosis was related to arachidonic acid metabolism, ether lipid metabolism, sphingolipid metabolism, glycerophospholipid metabolism and primary bile acid biosynthesis. Validation of the key targets by network pharmacology analysis of potential metabolic markers showed that AR significantly down-regulated the expression of CYP1B1 and up-regulated the expression of CYP1A2 and PCYT1A. Conclusion:Metabolomics combined with network pharmacology was used for the first time to clarify that the treatment of AR on liver fibrosis, which is related to the regulation of arachidonic acid metabolism and ether lipid metabolism by modulating the expression of CYP1A2, CYP1B1 and PCYT1A. And the integrated approach can provide new strategies and ideas for the study of molecular mechanisms of traditional Chinese medicines in the treatment of liver fibrosis.

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A Network Pharmacology Analysis to Explore the Effect of Astragali Radix-Radix Angelica Sinensis on Traumatic Brain Injury.

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A Network Pharmacology Analysis to Explore the Effect of <i>Astragali Radix-Radix Angelica Sinensis</i> on Traumatic Brain Injury.

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