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Exploring the mechanism of Icariin in the treatment of depression through BDNF-TrkB pathway based on network pharmacology

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Abstract

Depression has increasingly become a disease that seriously harms people’s mental health around the world. Icariin is the main active component of Epimedii Herba and effective on protecting the central nervous system. The purpose of this study was to explore the mechanism of icariin against depression based on network pharmacology and molecular docking. The potential targets related to icariin and depression were obtained by accessing network databases. The Metascape database was used for the enrichment analysis of GO function and KEGG pathways. A common target-pathway network was constructed using Cytoscape 3.9.0 software. Schrödinger Maestro 12.8 was adopted to evaluate the binding ability of icariin to core targets. Mice were induced by the chronic unpredictable mild stress (CUMS) model, and the prediction results of this study were verified by in vivo experiments. A total of 109 and 3294 targets were identified in icariin and depression, respectively. The common target-pathway network was constructed, and 7 core target genes were obtained. The molecular docking results of the 7 core target genes with icariin showed good affinity. In a CUMS-induced depression model, we found that icariin could effectively improve depression-like behavior of mice, increase the expression of monoamine neurotransmitters 5-hydroxytryptamine, dopamine, and norepinephrine, decrease the secretion of inflammatory factors tumor necrosis factor-α, interleukin-6, and interleukin-1β, and upregulate the relative expression levels of BDNF, p-TrkB/TrkB, p-Akt/Akt, p-CREB/CREB, MAPK3, MAPK1, Bcl-2, EGFR, and mTOR. The results suggest that icariin has certain antidepressant effects, and may be mediated by the BDNF-TrkB signaling pathway. It provides new ideas for the treatment of depression in the future.

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Data availability

The datasets used and/or analyzed during the current study are availability from the corresponding author on reasonable request.

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Funding

This work was supported by Hebei Natural Science Foundation (H2021209059) and Doctoral Research Foundation of North China University of Science and Technology (25759799).

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Authors and Affiliations

  1. School of Pharmacy, North China University of Science and Technology, Tangshan, 063210, Hebei Province, China

    Xiaoke Di, Meiyu Wan, Ya-nan Bai, Fengjuan Lu, Minghui Zhao, Zhifei Zhang & Yang Li

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  1. Xiaoke Di
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  2. Meiyu Wan
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  3. Ya-nan Bai
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  4. Fengjuan Lu
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  5. Minghui Zhao
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  6. Zhifei Zhang
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  7. Yang Li
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Contributions

XD and YL designed the project. XD, MW, FL, and MZ collected the data. XD and YB performed the data analysis. XD and MW made molecular docking analysis. XD prepared the original draft. YL finish the revision of the manuscript. All authors have read and approved the final manuscript. The authors declare that all data were generated in-house and that no paper mill was used.

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Correspondence to Yang Li.

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Di, X., Wan, M., Bai, Yn. et al. Exploring the mechanism of Icariin in the treatment of depression through BDNF-TrkB pathway based on network pharmacology. Naunyn-Schmiedeberg's Arch Pharmacol 397, 463–478 (2024). https://doi.org/10.1007/s00210-023-02615-1

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