Metabolomics coupled with SystemsDock reveal the protective effect and the potential active components of Naozhenning granule against traumatic brain injury

Cao, Jianhua; Ya-hui, Duan; Liu, Yanzhi; Liu, Haixia; Wei, Chunhong; Wang, Jiang; Qin, Xuemei; Wang, Xuwen; Li, Zhenyu

doi:10.1016/j.jep.2019.112247

Cited by 9 publications

(4 citation statements)

References 36 publications

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“…Uniprot was utilized for protein structure query. SystemsDock, a web server for network pharmacology-based prediction and analysis, was used for molecular docking in this study [ 16 ]. The PKd/PKi (dissociation constant) was calculated based on in silico molecular docking.…”

Section: Methodsmentioning

confidence: 99%

Predicting candidate therapeutic drugs for sepsis-induced acute respiratory distress syndrome based on transcriptome profiling

et al. 2021

Bioengineered

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Sepsis-induced acute respiratory distress syndrome (ARDS) remains a major threat to human health without effective therapeutic drugs. Previous studies demonstrated the power of gene expression profiling to reveal pathological changes associated with sepsis-induced ARDS. However, there is still a lack of systematic data mining framework for identifying potential targets for treatment. In this study, we demonstrated the feasibility of druggable targets prediction based on gene expression data. Through the functional enrichment analysis of microarray-based expression profiles between sepsis-induced ARDS and non-sepsis ARDS samples, we revealed genes involved in anti-microbial infection immunity were significantly altered in sepsis-induced ARDS. Protein-protein interaction (PPI) network analysis highlighted TOP2A gene as the key regulator in the dysregulated gene network of sepsis-induced ARDS. We were also able to predict several therapeutic drug candidates for sepsis-induced ARDS using Connectivity Map (Cmap) database, among which doxorubicin was identified to interact with TOP2A with a high affinity similar to its endogenous ligand. Overall, our findings suggest that doxorubicin could be a potential therapeutic for sepsis-induced ARDS by targeting TOP2A, which requires further investigation and validation. The whole study relies on publicly available dataset and publicly accessible database or bioinformatic tools for data mining. Therefore, our study benchmarks a workflow for druggable target prediction which can be widely applicable in the search of targets in other pathological conditions.

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Section: Methodsmentioning

confidence: 99%

Predicting candidate therapeutic drugs for sepsis-induced acute respiratory distress syndrome based on transcriptome profiling

et al. 2021

Bioengineered

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“…The SystemsDock website ( http://systemsdock.unit.oist.jp/iddp/home/index ) is a web server dedicated to the prediction and analysis of network pharmacology [ 34 ] and capable of validating whether a small-molecule compound binds tightly to a protein from the perspective of the interaction parameter. After initially submitting the PDB IDs of potential key molecules, we extracted 3D conformations of the components from the PubChem database ( https://pubchem.ncbi.nlm.nih.gov/ ) [ 35 ].…”

Section: Methodsmentioning

confidence: 99%

Network Pharmacology Analysis of the Therapeutic Mechanisms Underlying Beimu-Gualou Formula Activity against Bronchiectasis with In Silico Molecular Docking Validation

Shen

Zhou

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Background. The classical Chinese herbal prescription Beimu-Gualou formula (BMGLF) has been diffusely applied to the treatment of respiratory diseases, including bronchiectasis. Although concerning bronchiectasis the effects and mechanisms of action of the BMGLF constituents have been partially elucidated, it remains to be determined how the formula in its entirety exerts therapeutic effects. Methods. In this study, the multitarget mechanisms of BMGLF against bronchiectasis were predicted with network pharmacology analysis. Using prepared data, a drug-target interaction network was established and subsequently the core therapeutic targets of BMGLF were identified. Furthermore, the biological function and pathway enrichment of potential targets were analyzed to evaluate the therapeutic effects and pivotal signaling pathways of BMGLF. Finally, virtual molecular docking was performed to assess the affinities of compounds for the candidate targets. Results. The therapeutic action of BMGLF against bronchiectasis involves 18 core target proteins, including the aforementioned candidates (i.e., ALB, ICAM1, IL10, and MAPK1), which are assumed to be related to biological processes such as drug response, cellular response to lipopolysaccharide, immune response, and positive regulation of NF-κB activity in bronchiectasis. Among the top 20 signaling pathways identified, mechanisms of action appear to be primarily related to Chagas disease, allograft rejection, hepatitis B, and inflammatory bowel disease. Conclusion. In summary, using a network pharmacology approach, we initially predicted the complex regulatory profile of BMGLF against bronchiectasis in which multilink suppression of immune/inflammatory responses plays an essential role. These results may provide a basis for novel pharmacotherapeutic approaches for bronchiectasis.

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“…During large depth (>100 msw) saturation diving, the central nervous system is continuously exposed to oxidative stress due to the excessive production of reactive oxygen species (ROS) triggered by the heliox-saturation pressurized environment [23,24]. An imbalance between oxidant and antioxidant levels is a common metabolic regulatory element in various neurological disorders, including Alzheimer's disease [25], autism spectrum disorder [26], ischemic brain [21], traumatic brain injury [27], and so on [18,28,29]. The level changes of SOD, MDA, and Gpx, as recognized indicators for oxidative stress, reflect the oxygen free radical…”

Section: Oxidative Stress Analysismentioning

confidence: 99%

Oxidative stress, dysfunctional energy metabolism, and destabilizing neurotransmitters altered the cerebral metabolic profile in a rat model of simulated heliox saturation diving to 4.0 MPa

Liu

Fang²,

Xu³

et al. 2023

PLoS ONE

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The main objective of the present study was to determine metabolic profile changes in the brains of rats after simulated heliox saturated diving (HSD) to 400 meters of sea water compared to the blank controls. Alterations in the polar metabolome in the rat brain due to HSD were investigated in cortex, hippocampus, and striatum tissue samples by applying an NMR-based metabolomic approach coupled with biochemical detection in the cortex. The reduction in glutathione and taurine levels may hypothetically boost antioxidant defenses during saturation diving, which was also proven by the increased malondialdehyde level, the decreased superoxide dismutase, and the decreased glutathione peroxidase in the cortex. The concomitant decrease in aerobic metabolic pathways and anaerobic metabolic pathways comprised downregulated energy metabolism, which was also proven by the biochemical quantification of the metabolic enzymes Na-K ATPase and LDH in cerebral cortex tissue. The significant metabolic abnormalities of amino acid neurotransmitters, such as GABA, glycine, and aspartate, decreased aromatic amino acids, including tyrosine and phenylalanine, both of which are involved in the metabolism of dopamine and noradrenaline, which are downregulated in the cortex. Particularly, a decline in the level of N-acetyl aspartate is associated with neuronal damage. In summary, hyperbaric decompression of a 400 msw HSD affected the brain metabolome in a rat model, potentially including a broad range of disturbing amino acid homeostasis, metabolites related to oxidative stress and energy metabolism, and destabilizing neurotransmitter components. These disturbances may contribute to the neurochemical and neurological phenotypes of HSD.

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Metabolomics coupled with SystemsDock reveal the protective effect and the potential active components of Naozhenning granule against traumatic brain injury

Cited by 9 publications

References 36 publications

Predicting candidate therapeutic drugs for sepsis-induced acute respiratory distress syndrome based on transcriptome profiling

Predicting candidate therapeutic drugs for sepsis-induced acute respiratory distress syndrome based on transcriptome profiling

Network Pharmacology Analysis of the Therapeutic Mechanisms Underlying Beimu-Gualou Formula Activity against Bronchiectasis with In Silico Molecular Docking Validation

Oxidative stress, dysfunctional energy metabolism, and destabilizing neurotransmitters altered the cerebral metabolic profile in a rat model of simulated heliox saturation diving to 4.0 MPa

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