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

mechanisms through which FT may exert its therapeutic Investigation: All authors
effects on MDD. In addition, molecular docking studies Methodology: All authors
reinforced the therapeutic relevance of FT’s active Writing–original draft: All authors
components and their interactions with the identified Writing–review & editing: Tahmineh Mokhtari
targets. The findings unveiled a complex web of interactions
between FT and its respective targets. We identified five Ethics approval and consent to participate
specific bioactive components of FT – GSK3B, MAOA, Not applicable.
ACHE, MMP9, and MPO – that demonstrated promising
efficacy in treating MDD by modulating pathways related Consent for publication
to the proinflammatory cytokine IL-17. Importantly, our
comparative analysis with FLX highlighted FT’s superior Not applicable.
binding affinities, particularly with MAOA and MPO, Availability of data
suggesting that FT may offer enhanced therapeutic effects.
This investigation underscores the potential of FT as a The data that support the findings of this study are available
multi-target therapeutic agent for the management of from the corresponding author on reasonable request.
MDD. The study’s findings provide a solid foundation for
further exploration of FT’s therapeutic applications and the References
underlying mechanisms responsible for its beneficial effects 1. Otte C, Gold SM, Penninx BW, et al. Major depressive
in MDD and related neuropsychiatric disorders. Although disorder. Nat Rev Dis Primers. 2016;2(1):16065.
FT has a limited ability to cross the BBB, it can be potentially
delivered using nanoparticles, enhancing its therapeutic doi: 10.1038/nrdp.2016.65
potential. However, it is crucial to note that studies of this 2. Liu L, Liu C, Wang Y, Wang P, Li Y, Li B. Herbal medicine
nature require validations from animal models to confirm for anxiety, depression and insomnia. Curr Neuropharmacol.
the efficacy and safety of FT in vivo. This represents a 2015;13(4):481-493.
limitation of our current study, as in vitro tests and follow-up doi: 10.2174/1570159X1304150831122734
studies are necessary to validate our findings and further World Health Organization. Depression and Other Common
elucidate the mechanisms by which FT improves MDD by 3. Mental Disorders: Global Health Estimates. Geneva,
interfering with the IL-17 signaling pathway and reducing Switzerland: World Health Organization; 2017.
the expression of proinflammatory targets. Overall, while
our research highlights FT’s promising potential, the lack 4. Santomauro DF, Herrera AMM, Shadid J, et al. Global
of experimental validation limits its translational relevance. prevalence and burden of depressive and anxiety disorders in
Future experimental studies are essential to validate our 204 countries and territories in 2020 due to the COVID-19
in silico findings and explore FT’s role as a novel therapeutic pandemic. Lancet. 2021;398(10312):1700-1712.
agent in treating depression. doi: 10.1016/S0140-6736(21)02143-7
Acknowledgments 5. Elzamzamy, K., & Khan, Y. S. (2022). Major depressive and
dysthymic disorders. J Alternative Med Research, 14(3):
None. 309-324.
Funding 6. Bhatt S, Nagappa AN, Patil CR. Role of oxidative stress in
depression. Drug Discov Today. 2020;25(7):1270-1276.
This study was funded by the Faculty Development Grants doi: 10.1016/j.drudis.2020.05.001
from Hubei University of Medicine (No. 2023QDJZR) to
Tahmineh Mokhtari. 7. Beck AT, Alford BA. Depression: Causes and Treatment.
Philadelphia, PA: University of Pennsylvania Press; 2009.
Conflict of interest 8. Seifert J, Maier HB, Führmann F, et al. Pharmacological
Tahmineh Mokhtari is the Editorial Board Member of the treatment of major depressive disorder according to
journal but was not in any way involved in the editorial severity in psychiatric inpatients: Results from the AMSP
and peer-review process conducted for this paper, directly pharmacovigilance program from 2001-2017. J Neural
or indirectly. Other authors declare no conflicts of interest. Transm (Vienna). 2022;129(7):925-944.
doi: 10.1007/s00702-022-02504-6
Author contributions
9. Mokhtari T. Targeting autophagy and neuroinflammation
Conceptualization: Tahmineh Mokhtari pathways with plant‐derived natural compounds as potential
Formal analysis: Tahmineh Mokhtari antidepressant agents. Phytother Res. 2022;36(9):3470-3489.

Volume 4 Issue 1 (2025) 10 doi: 10.36922/gpd.4846