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      A network pharmacology study on mechanism of resveratrol in treating preeclampsia via regulation of AGE-RAGE and HIF-1 signalling pathways

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          Abstract

          Background

          Preeclampsia (PE) is a hypertensive disorder of pregnancy that threatens the lives of millions of pregnant women and their babies worldwide. Without effective medications, there are thousands of maternal and child mortalities every year. Resveratrol (RSV), a non-flavonoid polyphenol extracted from multiple plants, has shown positive effects in treating hypertension, cardiovascular disorders, and even PE. This study aimed to explore the pharmacological mechanism of RSV in treating PE by using network pharmacology and bioinformatics.

          Methods

          With the use of multiple databases, 66 intersecting targets were obtained from the 347 putative targets of RSV and 526 PE-related genes. Then, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted to investigate the functions of the intersecting targets. The protein–protein interaction network and target–pathway network were drawn and analyzed to illustrate the correlation between targets and pathways. Finally, molecular docking was conducted to calculate the binding energy between RSV and core targets.

          Results

          The results showed that the core targets of RSV were IL6, TNF, IL1B, VEGFA, STAT3, and EGFR. There existed good binding between RSV and IL6, TNF, IL1B, VEGFA, and EGFR. In addition, we found that RSV mainly functioned in the AGE-RAGE and HIF-1 signaling pathways, which are associated with the occurrence and development of PE.

          Conclusion

          In conclusion, our findings indicated that RSV has the effects of regulating angiogenesis and anti-inflammation and can be a candidate medicine for treating PE.

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          Most cited references80

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          Cytoscape: a software environment for integrated models of biomolecular interaction networks.

          Cytoscape is an open source software project for integrating biomolecular interaction networks with high-throughput expression data and other molecular states into a unified conceptual framework. Although applicable to any system of molecular components and interactions, Cytoscape is most powerful when used in conjunction with large databases of protein-protein, protein-DNA, and genetic interactions that are increasingly available for humans and model organisms. Cytoscape's software Core provides basic functionality to layout and query the network; to visually integrate the network with expression profiles, phenotypes, and other molecular states; and to link the network to databases of functional annotations. The Core is extensible through a straightforward plug-in architecture, allowing rapid development of additional computational analyses and features. Several case studies of Cytoscape plug-ins are surveyed, including a search for interaction pathways correlating with changes in gene expression, a study of protein complexes involved in cellular recovery to DNA damage, inference of a combined physical/functional interaction network for Halobacterium, and an interface to detailed stochastic/kinetic gene regulatory models.
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            Metascape provides a biologist-oriented resource for the analysis of systems-level datasets

            A critical component in the interpretation of systems-level studies is the inference of enriched biological pathways and protein complexes contained within OMICs datasets. Successful analysis requires the integration of a broad set of current biological databases and the application of a robust analytical pipeline to produce readily interpretable results. Metascape is a web-based portal designed to provide a comprehensive gene list annotation and analysis resource for experimental biologists. In terms of design features, Metascape combines functional enrichment, interactome analysis, gene annotation, and membership search to leverage over 40 independent knowledgebases within one integrated portal. Additionally, it facilitates comparative analyses of datasets across multiple independent and orthogonal experiments. Metascape provides a significantly simplified user experience through a one-click Express Analysis interface to generate interpretable outputs. Taken together, Metascape is an effective and efficient tool for experimental biologists to comprehensively analyze and interpret OMICs-based studies in the big data era.
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              The Protein Data Bank.

              The Protein Data Bank (PDB; http://www.rcsb.org/pdb/ ) is the single worldwide archive of structural data of biological macromolecules. This paper describes the goals of the PDB, the systems in place for data deposition and access, how to obtain further information, and near-term plans for the future development of the resource.
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                Author and article information

                Contributors
                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                1664-2392
                05 January 2023
                2022
                : 13
                : 1044775
                Affiliations
                [1] 1 Health Science Center, Xi'an Jiaotong University , Xi’an, Shaanxi, China
                [2] 2 Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Health Science Center, Xi’an Jiaotong University , Xi’an, Shaanxi, China
                [3] 3 College of Medicine & Forensics, Health Science Center, Xi'an Jiaotong University , Xi’an, Shaanxi, China
                Author notes

                Edited by: Antonio Brunetti, Magna Græcia University, Italy

                Reviewed by: Yike Yang, Peking University Third Hospital, China; Maria Mirabelli, University Magna Graecia of Catanzaro, Italy

                This article was submitted to Systems Endocrinology, a section of the journal Frontiers in Endocrinology

                Article
                10.3389/fendo.2022.1044775
                9849370
                36686428
                131fb479-c52c-45ef-be45-37144ab0fedf
                Copyright © 2023 Shi, Wang, Jia and Sun

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 17 September 2022
                : 13 December 2022
                Page count
                Figures: 6, Tables: 2, Equations: 0, References: 80, Pages: 12, Words: 4634
                Categories
                Endocrinology
                Original Research

                Endocrinology & Diabetes
                resveratrol (rsv),preeclampsia (pe),network pharmacology,bioinformatics,molecular docking

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