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

A B

C D

Figure 3. GO and KEGG enrichment analysis for FT targets in the treatment of MDD. Bar plots for GO enrichment include (A) biological process,
(B) cellular component, and (C) molecular function, along with (D) a dot plot for KEGG enrichment.
Abbreviations: FT: Fisetin; GO: Gene Ontology; IL: Interleukin; KEGG: Kyoto Encyclopedia of Genes and Genomes; MDD: Major depressive disorder;
Proc: Process; Reg: Regulation.

specialized databases and computational tools to evaluate by oxytosis (oxidative stress-induced cell death) and
the pharmacokinetic profile, DL attributes, permeability ferroptosis (iron-dependent cell death); this positions FT
across the BBB, detailed compound information, and as a potential therapeutic target for mitigating various age-
potential toxicological risks associated with FT. related pathological processes. 32,33 The analysis of GO and
Our findings indicated that FT has beneficial medicinal KEGG pathways identified multiple signaling pathways
properties with a DL score of 0.24 and good absorption that FT may regulate in the treatment of MDD. A notable
following oral administration. However, it has a negative discovery from the research was the identification of the
BBB permeability score of −0.69, suggesting a limited ability IL-17 signaling pathway as a significant common target
to cross the BBB. Therefore, its delivery likely requires related to MDD. The cytokine IL-17 plays a significant
the use of transporting nanoparticles. The compound role in the central nervous system (CNS) and its associated
exhibited neurotoxicity and immunotoxicity, suggesting pathological processes. IL-17 acts on multiple resident
its potential as a therapeutic agent for neuroinflammatory cells within the CNS, including neurons, astrocytes, and
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diseases such as MDD, AD, traumatic brain injury, microglia, to enhance the neuroinflammatory response.
Parkinson’s disease (PD), schizophrenia, stroke, vascular Furthermore, Ling et al. (2023) conducted comprehensive
dementia, and diabetic neuropathy. According to the research aimed at predicting FT targets for reversing
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study by Currais et al., the compound FT has been cisplatin resistance using bioinformatics methodologies.
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found to have several beneficial effects in rapidly aging They found that FT might inhibit the chemoresistance of
mice, including decreasing inflammation, reducing the head and neck cancer cells to cisplatin by targeting the
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number of senescent cells, and lowering oxidative stress. HSP90AA1/IL-17 pathway. FT may also alleviate MDD
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In addition, the research has shown that FT can regulate by inhibiting IL-17 as a proinflammatory cytokine and
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key signaling pathways induced by neurotrophic factors, enhancing the release and activation of macrophages.
suggesting its potential as a promising neuroprotective The study suggests that by modulating the IL-17
compound capable of preventing cell death mediated signaling pathway, FT may exert neuroprotective and

Volume 4 Issue 1 (2025) 7 doi: 10.36922/gpd.4846