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Broussonin E against acute respiratory distress syndrome: the potential roles of anti-inflammatory

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Abstract

We applied network pharmacology and molecular docking analyses to study the efficacy of Broussonin E (BRE) in acute respiratory distress syndrome (ARDS) treatment and to determine the core components, potential targets, and mechanism of action of BRE. The SwissTargetprediction and SEA databases were used to predict BRE targets, and the GeneCards and OMIM databases were used to predict ARDS-related genes. The drug targets and disease targets were mapped to obtain an intersecting drug target gene network, which was then uploaded into the String database for protein–protein interaction network analysis. The intersecting gene was also uploaded into the DAVID database for gene ontology enrichment analysis and Kyoto encyclopedia of genes and genomes pathway analysis. Molecular docking analysis was performed to verify the interaction of BRE with the key targets. Finally, to validate the experiment in vivo, we established an oleic acid-induced ARDS rat model and evaluated the protective effect of BRE on ARDS by histological evaluation and enzyme-linked immunosorbent assay. Overall, 79 targets of BRE and 3974 targets of ARDS were predicted, and 79 targets were obtained after intersection. Key genes such as HSP90AA1, JUN, ESR1, MTOR, and PIK3CA play important roles in the nucleus and cytoplasm by regulating the tumor necrosis factor, nuclear factor-κB, and PI3K-Akt signaling pathways. Molecular docking results showed that small molecules of BRE could freely bind to the active site of the target proteins. In vivo experiments showed that BRE could reduce ARDS-related histopathological changes, release of inflammatory factors, and infiltration of macrophages and oxidative stress reaction. BRE exerts its therapeutic effect on ARDS through target and multiple pathways. This study also predicted the potential mechanism of BRE on ARDS, which provides the theoretical basis for in-depth and comprehensive studies of BRE treatment on ARDS.

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Data availability

The datasets generated and/or analyzed during the current study are not publicly available due to subsequent experiments that have not been completed but are available from the corresponding author on reasonable request.

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Funding

This work was supported by the National Natural Science Foundation of China (81800319), the Basic and Clinical Cooperative Research Promotion Program of Anhui Medical University (2020xkjT046), the Research Fund of Anhui Medical University (2019xkj144, 2020xkj047), the Open Research fund of Key Laboratory of Anesthesiology and Perioperative Medicine of Anhui Higher Education Institutes, Anhui Medical University (MZKF202003), and the Anhui Public Health Clinical Center Scientific Research Cultivating Fund (2022YKJ05, 2023YKJ10).

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Author notes

  1. Ning Wang, Guangcheng Sun, Qiaoyun Zhang, Jian Huang, Ruguo Ren, Chunhui Wang, and Chen Chen have contributed equally to this work.

Authors and Affiliations

  1. Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University and Anhui Public Health Clinical Center, Xinzhan District, No.100, Huaihai Road, Hefei, 230011, Anhui, China

    Ning Wang, Qiaoyun Zhang, Qian Gao, Bingjie Wang, Lingling Guo, Gao Cheng, Yuexia Hu, Chunhui Wang & Chen Chen

  2. Department of Cardiology, Anhui Chest Hospital, Hefei, Anhui, China

    Guangcheng Sun

  3. Department of Genetics, School of Life Science, Anhui Medical University, Hefei, Anhui, China

    Qian Gao

  4. Department of Thoracic Surgery, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, No.17, Lujiang Road, Luyang District, Hefei, 230001, Anhui, China

    Jian Huang

  5. Department of Cardiovascular Hospital, Xi’an No.1 Hospital and The First Affiliated Hospital of Northwest University, Beilin District, No.30, South Street powder Lane, Xi’an, 710002, Shaanxi, China

    Ruguo Ren

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  1. Ning Wang
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Contributions

All authors contributed to the study conception and design, and approved the final manuscript. Conceptualization, resources acquisition, methodology, project administration, data analysis, and roles/writing—original draft and writing—review and editing were performed by C.C., C.H.W., R.G.R., J.H., and N.W. The histological analysis, material preparation, and data collection were performed by N.W., G.C.S., and Q.Y.Z. Q.G., B.J.W., L.L.G., Y.X.H., and G.C. performed the statistical analysis. The investigation, methodology, data collection, and analysis were performed by N.W., G.C.S., and Q.Y.Z. All authors contributed to the article and approved the submitted version. The authors declare that all data were generated in-house and that no paper mill was used.

Corresponding authors

Correspondence to Jian Huang, Ruguo Ren, Chunhui Wang or Chen Chen.

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The animal study was reviewed and approved by Committee of Ethics on Animal Experiments at the Anhui Medical University.

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Wang, N., Sun, G., Zhang, Q. et al. Broussonin E against acute respiratory distress syndrome: the potential roles of anti-inflammatory. Naunyn-Schmiedeberg's Arch Pharmacol 397, 3195–3209 (2024). https://doi.org/10.1007/s00210-023-02801-1

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