AccScience Publishing / GPD / Online First / DOI: 10.36922/gpd.4846
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ORIGINAL RESEARCH ARTICLE

Antidepressant effects of fisetin: Identifying molecular mechanisms by network pharmacology and molecular docking

Golnaz Shafiei1 ,  Mahnaz Poorhassan2 ,  Tahmineh Mokhtari3*
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1 Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
2 Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3 Department of Histology and Embryology, Faculty of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China
GPD, 4846 https://doi.org/10.36922/gpd.4846
Submitted: 13 September 2024 | Revised: 17 December 2024 | Accepted: 23 December 2024 | Published: 10 January 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Major depressive disorder (MDD) is a heterogeneous condition influenced by a complex interplay of social, psychological, and biological factors. Fisetin (FT), a flavonoid polyphenol found in various plants, has demonstrated neuroprotective properties that may be beneficial in treating MDD. This research aims to evaluate the potential molecular mechanisms of FT in treating MDD using network pharmacology analysis, with validation through molecular docking methods. We assessed the drug-like properties of FT using the TCMSP and SwissADME platforms. Potential drug targets for FT were identified through SuperPred and SwissTargetPrediction. We compiled MDD-associated targets from established databases and identified common genes shared between FT and MDD. The common targets were analyzed for protein-protein interactions using the STRING database to identify essential targets. Consequently, these key targets were further investigated through Kyoto Encyclopedia of Genes and Genomes and Gene Ontology (GO) enrichment analyses with the help of ShinyGO software. The results indicated that FT targets are linked to specific pathways involved in the pathogenesis of MDD, with the IL-17 signaling pathway emerging as a significant pathway of interest. Strong binding affinities were found between FT and key proteins, including glycogen synthase kinase 3 beta, monoamine oxidase A, acetylcholinesterase, matrix metalloproteinase 9, and myeloperoxidase, suggesting that FT may serve as a promising therapeutic agent for MDD by targeting components of the IL-17 pathway. In conclusion, this research successfully employed computational methods to elucidate the potential effectiveness of FT in managing MDD. It offered important perspectives on the regulatory mechanisms involved and emphasized the IL-17 signaling pathway as a possible target for MDD therapy.

Keywords
Major depressive disorder
Fisetin
Traditional Chinese medicine
Network pharmacology
Molecular docking
Funding
This study was funded by the Faculty Development Grants from Hubei University of Medicine (No. 2023QDJZR) to Tahmineh Mokhtari.
Conflict of interest
Tahmineh Mokhtari is the Editorial Board Member of the journal but was not in any way involved in the editorial and peer-review process conducted for this paper, directly or indirectly. Other authors declare no conflicts of interest.
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