Page 123 - GPD-4-1

Gene & Protein in Disease

ORIGINAL RESEARCH ARTICLE
Antidepressant effects of fisetin: Identifying

molecular mechanisms by network
pharmacology and molecular docking

Golnaz Shafiei 1 , Mahnaz Poorhassan 2 , and Tahmineh Mokhtari *
3
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

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
*Corresponding author: MDD-associated targets from established databases and identified common genes
Tahmineh Mokhtari shared between FT and MDD. The common targets were analyzed for protein-protein
(makhtari.tmn@hbmu.edu.cn) interactions using the STRING database to identify essential targets. Consequently,
Citation: Shafiei G, Poorhassan M, these key targets were further investigated through Kyoto Encyclopedia of Genes and
Mokhtari T. Antidepressant Genomes and Gene Ontology (GO) enrichment analyses with the help of ShinyGO
effects of fisetin: Identifying software. The results indicated that FT targets are linked to specific pathways
molecular mechanisms by network
pharmacology and molecular involved in the pathogenesis of MDD, with the IL-17 signaling pathway emerging as
docking. Gene Protein Dis. a significant pathway of interest. Strong binding affinities were found between FT
2025;4(1):4846. and key proteins, including glycogen synthase kinase 3 beta, monoamine oxidase A,
doi: 10.36922/gpd.4846
acetylcholinesterase, matrix metalloproteinase 9, and myeloperoxidase, suggesting
Received: September 13, 2024 that FT may serve as a promising therapeutic agent for MDD by targeting components
Revised: December 17, 2024
Accepted: December 23, 2024 of the IL-17 pathway. In conclusion, this research successfully employed computational
Published online: January 10, methods to elucidate the potential effectiveness of FT in managing MDD. It offered
2025 important perspectives on the regulatory mechanisms involved and emphasized the
Copyright: © 2025 Author(s). IL-17 signaling pathway as a possible target for MDD therapy.
This is an Open-Access article
distributed under the terms of the
Creative Commons Attribution Keywords: Major depressive disorder; Fisetin; Traditional Chinese medicine; Network
License, permitting distribution,
and reproduction in any medium, pharmacology; Molecular docking
provided the original work is
properly cited.
Publisher’s Note: AccScience
Publishing remains neutral with 1. Introduction
regard to jurisdictional claims in
published maps and institutional Modern society is witnessing a variety of psychiatric disorders, with major depressive
affiliations. disorder (MDD) being a highly prevalent form that leads to significant disability and

Volume 4 Issue 1 (2025) 1 doi: 10.36922/gpd.4846