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Gene & Protein in Disease In silico insights on fisetin’s antidepressant effects

Figure 4. Docking analysis of FT with five key targets implicated in MDD, compared to the established antidepressant FLX. The values display the affinity
scores between ligands and receptors, illustrating the strength of their interactions.
Abbreviations: ACHE: Acetylcholinesterase; FLX: Fluoxetine; FT: Fisetin; GSK3B: Glycogen synthase kinase 3 beta; MAOA: Monoamine oxidase A;
MDD: Major depressive disorder; MMP9: Matrix metalloproteinase 9; MPO: Myeloperoxidase.

anti-inflammatory actions, which could be beneficial in the MMP2, ABCB1, CDK5, and CDK5R1. These identified
treatment of MDD and other neurodegenerative diseases. target genes are involved in various cellular functions

To delve deeper into the mechanism by which the and signaling pathways, offering important insights into
bioactive compound FT operates, we performed an the molecular targets and mechanisms through which FT
extensive analysis aimed at identifying the target genes may provide therapeutic benefits in MDD and potentially
linked to its effects. This investigation revealed a total of other neurological conditions. For instance, one of the
1,805 genes associated with MDD and 50 genes related to key target proteins identified in the analysis was GSK3B.
FT. Significantly, 17 of these genes were found to overlap GSK3B is a versatile protein that modulates a diverse array
between MDD and FT, suggesting the possibility of shared of cellular processes, including apoptosis (programmed
pathways and mechanisms in MDD treatment. To identify cell death) and cell survival. It plays a crucial role in
the crucial genes that contribute to FT’s therapeutic effects, the signal transduction cascades that regulate neuronal
the researchers employed network pharmacology and cell development and energy metabolism within the
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PPI analyses. As a result, they pinpointed 10 key target CNS. Moreover, the MAOA gene, as an important
proteins: GSK3B, MAOA, ACHE, MMP9, MPO, XDH, candidate gene for depressive symptoms, interacts with

Volume 4 Issue 1 (2025) 8 doi: 10.36922/gpd.4846