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

A B

A

B

C

D

C

Figure 2. PPI network and key targets of FT in the treatment of MDD. (A) STRING data; (B) data visualization through Cytoscape; and (C) identification
of the top target proteins.
Abbreviations: FT: Fisetin; MDD: Major depressive disorder; PPI: Protein-protein interaction.

Table 2. Top 10 targets of PPI network have been observed in both their blood and cerebrospinal
fluid. As a result, reducing neuroinflammation has
15
Targets Degree Betweenness Closeness emerged as a promising approach for treating MDD.
1 GSK3B 8.0 95.33 0.65
2 MAOA 5.0 55.66 0.55 FT functions as a potential anti-inflammatory agent
3 ACHE 5.0 29.66 0.55 by inhibiting the upstream phosphorylation of IκBα and
4 MMP9 5.0 18.0 0.53 NF-κB. It also acts as an antioxidant by enhancing the
5 MPO 4.0 29.0 0.45 expression of antioxidant factors through extracellular signal-
regulated kinase phosphorylation. This compound is likely
31
6 XDH 4.0 26.0 0.51 to serve as a therapeutic agent for various neuroinflammatory
7 MMP2 4.0 11.33 0.51 conditions, including mood disorders and AD. This
32
8 ABCB1 4.0 28.0 0.5 comprehensive study employed a multifaceted approach
9 CDK5 3.0 2.16 0.457 to thoroughly investigate the antidepressant therapeutic
10 CDK5R1 2.0 0.0 0.416 potential of the TCM compound FT. Using the power of
Abbreviations: ABCB1: Adenosine triphosphate-binding network pharmacology and in silico molecular docking
cassette sub-family B member 1; ACHE: Acetylcholinesterase; techniques, the researchers set out to elucidate the
CDK: Cyclin-dependent kinase; CDK5R1: CDK 5 regulatory underlying molecular mechanisms and pathways through
subunit 1 FLX: Fluoxetine; GSK3B: Glycogen synthase kinase 3 beta;
MAOA: Monoamine oxidase A; MMP: Matrix metalloproteinase; which FT may exert its beneficial effects in the context
MPO: Myeloperoxidase; XDH: Xanthine dehydrogenase. of MDD. The study began by employing a variety of

Volume 4 Issue 1 (2025) 6 doi: 10.36922/gpd.4846