Dataset Information

Systems Pharmacology-Dissection of the Molecular Mechanisms of Dragon's Blood in Improving Ischemic Stroke Prognosis.

ABSTRACT:

Materials and methods

(1) Based on system-pharmacology platform, the potential active compounds of DB are screened out according to ADME. (2) The ischemic stroke-related targets are predicted by utilizing these active compounds as probes, mapping the targets to the CTD database to establish a molecular-target-disease network. (3) To analyze the mechanism of DB treatment for the prognosis of ischemic stroke, we used the Metascape and DAVID databases to construct "ischemic stroke pathways". (4) PC12 cells were used to explore the protective effect of loureirin B on oxygen-glucose deprivation/reperfusion (OGD/R) injury, and BV-2 cells were used to determine the anti-inflammation effect of 4',7-dihydroxyflavone.

Results

Finally, we obtained 38 active compounds and 58 stroke-related targets. Network and pathway analysis indicate that DB is effective in the treatment of ischemic stroke by enhancing cell survival and inhibiting inflammatory and antiplatelet activation. In in vitro experiments, the main component loureirin B promoted the expression of HO-1 and Bcl-2 via positive regulation of PI3K/AKT/CREB and Nrf2 signaling pathways in PC12 cells against OGD/R damage. And the anti-in?ammatory activity of 4',7-dihydroxyflavone was related to the inhibition of COX-2, TNF-?, and IL-6 in LPS-induced BV-2 cells.

Conclusions

In our study, the results illustrated that DB in improving ischemic stroke prognosis may involve enhancing cell survival and antioxidant, anti-inflammation, and antiplatelet activities.

SUBMITTER: Jiang M

PROVIDER: S-EPMC7251463 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Systems Pharmacology-Dissection of the Molecular Mechanisms of Dragon's Blood in Improving Ischemic Stroke Prognosis.

Jiang Meng M Su Xing X Liu Jianling J Zheng Chunli C Li Xiaogang X

Evidence-based complementary and alternative medicine : eCAM 20200517

<h4>Materials and methods</h4>(1) Based on system-pharmacology platform, the potential active compounds of DB are screened out according to ADME. (2) The ischemic stroke-related targets are predicted by utilizing these active compounds as probes, mapping the targets to the CTD database to establish a molecular-target-disease network. (3) To analyze the mechanism of DB treatment for the prognosis of ischemic stroke, we used the Metascape and DAVID databases to construct "ischemic stroke pathways" ...[more]

PMID: 32508949

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Project description:BackgroundThe growing discipline of structural systems pharmacology is applied prospectively in this study to predict pharmacological outcomes of antibacterial compounds in Escherichia coli K12. This work builds upon previously established methods for structural prediction of ligand binding pockets on protein molecules and utilizes and expands upon the previously developed genome scale model of metabolism integrated with protein structures (GEM-PRO) for E. coli, structurally accounting for protein complexes. Carefully selected case studies are demonstrated to display the potential for this structural systems pharmacology framework in discovery and development of antibacterial compounds.ResultsThe prediction framework for antibacterial activity of compounds was validated for a control set of well-studied compounds, recapitulating experimentally-determined protein binding interactions and deleterious growth phenotypes resulting from these interactions. The antibacterial activity of fosfomycin, sulfathiazole, and trimethoprim were accurately predicted, and as a negative control glucose was found to have no predicted antibacterial activity. Previously uncharacterized mechanisms of action were predicted for compounds with known antibacterial properties, including (1-hydroxyheptane-1,1-diyl)bis(phosphonic acid) and cholesteryl oleate. Five candidate inhibitors were predicted for a desirable target protein without any known inhibitors, tryptophan synthase ? subunit (TrpB). In addition to the predictions presented, this effort also included significant expansion of the previously developed GEM-PRO to account for physiological assemblies of protein complex structures with activities included in the E. coli K12 metabolic network.ConclusionsThe structural systems pharmacology framework presented in this study was shown to be effective in the prediction of molecular mechanisms of antibacterial compounds. The study provides a promising proof of principle for such an approach to antibacterial development and raises specific molecular and systemic hypotheses about antibacterials that are amenable to experimental testing. This framework, and perhaps also the specific predictions of antibacterials, is extensible to developing antibacterial treatments for pathogenic E. coli and other bacterial pathogens.

Dataset Information

Systems Pharmacology-Dissection of the Molecular Mechanisms of Dragon's Blood in Improving Ischemic Stroke Prognosis.

Materials and methods

Results

Conclusions

Publications

Systems Pharmacology-Dissection of the Molecular Mechanisms of Dragon's Blood in Improving Ischemic Stroke Prognosis.

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