Fisetin as a Senotherapeutic Agent: Biopharmaceutical Properties and Crosstalk between Cell Senescence and Neuroprotection
Open accessAbstract
Like other organs, brain functions diminish with age. Furthermore, for a variety of neurological disorders—including Alzheimer’s disease—age is one of the higher-risk factors. Since in many Western countries the average age is increasing, determining approaches for decreasing the effects of aging on brain function is taking on a new urgency. Neuroinflammation and oxidative stress are two convoluted key factors in brain aging and chronic neurodegenerative diseases. The diverseness of factors, causing an age-related decrease in brain functions, requires identifying small molecules that have multiple biological activities that can affect all these factors. One great source of these small molecules is related to polyphenolic flavonoids. Recently, 3,3′,4′,7-tetrahydroxyflavone (fisetin) has been reported as a potent senotherapeutic capable of extending lifespan by reducing peroxidation levels and enhancing antioxidant cell responses. The neuroprotective effects of fisetin have been shown in several in vitro and in vivo models of neurological disorders due to its actions on multiple pathways associated with different neurological disorders. The present work aims to collect the most recent achievements related to the antioxidant and neuroprotective effects of fisetin. Moreover, in silico pharmacokinetics, pharmacodynamics, and toxicity of fisetin are also comprehensively described along with emerging novel drug delivery strategies for the amelioration of this flavonol bioavailability and chemical stability.
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Senomorphics revert or slow down senescence by regulating the SASP.
“senomorphics revert or slow down senescence by regulating the SASP [29]”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [29]
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Alzheimer’s Disease: A Contextual Link with Nitric Oxide Synthase
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Epigenetic Target Profiler: A Web Server to Predict Epigenetic Targets of Small Molecules
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The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence
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Effects of Fisetin Treatment on Cellular Senescence of Various Tissues and Organs of Old Sheep
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Kaempferol and Fisetin-Related Signaling Pathways Induce Apoptosis in Head and Neck Cancer Cells
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Fisetin, a potential skin rejuvenation drug that eliminates senescent cells in the dermis
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Revolutionizing Diabetic Foot Ulcer Care: The Senotherapeutic Approach
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Tissue factor links inflammation, thrombosis, and senescence in COVID-19
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Mitochondrial Aging and Senolytic Natural Products with Protective Potential
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New Trends in Aging Drug Discovery
Benhamú, B., Martín‐Fontecha, M., Vázquez‐Villa, H., López-Rodríguez, M. L., & Ortega‐Gutiérrez, S. (2022) · Biomedicines · doi:10.3390/biomedicines10082006 · Cited by 20 · see citing works
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Fisetin from Dietary Supplement to a Drug Candidate: An Assessment of Potential
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Flavonoids Derived from Chinese Medicine: Potential Neuroprotective Agents
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Body Composition and Senescence: Impact of Polyphenols on Aging-Associated Events
dos Santos, T. W., Pereira, Q. C., Fortunato, I. M., Oliveira, F. D. S., Alvarez, M. C., & Ribeiro, M. L. (2024) · Nutrients · doi:10.3390/nu16213621 · Cited by 10 · see citing works
Cellular Senescence and Senolytic Agents: Recent Updates on Their Role and Applications
Chandrakar, L., Ambatwar, R., & Khatik, G. L. (2023) · Current Topics in Medicinal Chemistry · doi:10.2174/0115680266273698231107110956 · Cited by 10 · see citing works
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Sokal, A., Stocerz, K., Olczyk, P., & Kadela-Tomanek, M. (2024) · Annales Academiae Medicae Silesiensis · doi:10.18794/aams/175007 · Cited by 5 · see citing works
Senolytic drugs: implications for clinical practice
Константиновна, И. А., Matchekhina, L. V., Ткачева, О. Н., Владимировна, Б. А., Melnitskaia, A. A., Churov, A. V., & Strazhesko, I. D. (2023) · Problems of Geroscience · doi:10.37586/2949-4745-1-2023-7-14 · Cited by 6 · see citing works
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Santos, T. B., Canuto, A. D. S. C. L., Meira, J. F. B. V. D. C., Santos-Diniz, A. C., Ribeiro, R. M. D. A. C., Paschoal, C. R. S., Rabelo, V. W., Abreu, P. A., Ferreira, V. F., da Rocha, D. R., et al. (2025) · ACS Omega · doi:10.1021/acsomega.5c06730 · Cited by 2 · see citing works
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Salas-Venegas, V., López‐Díazguerrero, N. E., Carreto, R. J. R., Königsberg, M., & Chavarría, A. (2026) · Frontiers in Nutrition · doi:10.3389/fnut.2026.1824908 · Cited by 2 · see citing works
Functional properties of foods in chronic kidney disease
Cardozo, L., Stenvinkel, P., & Mafra, D. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-91747-6.00008-1 · Cited by 2 · see citing works
Ciurleo, G. C. V., de Azevedo, O. G. R., Carvalho, C. G. M., Vitek, M. P., Warren, C. A., Guerrant, R. L., & Oriá, R. B. (2024) · Clinical Nutrition ESPEN · doi:10.1016/j.clnesp.2024.09.004 · Cited by 2 · see citing works
Goyal, K., Babu, M. A., Afzal, M., Rekha, A., Ali, H., Gupta, S., Singh, R. P., Mishra, A., Singh, H., Agrawal, M., et al. (2025) · Journal of Complementary and Integrative Medicine · doi:10.1515/jcim-2024-0444 · Cited by 2 · see citing works
Senolytic Drugs: Implications for Clinical Practice
Константиновна, И. А., Matchekhina, L. V., Tkacheva, O. N., Владимировна, Б. А., Melnitskaia, A. A., Churov, A. V., & Strazhesko, I. D. (2023) · Advances in Gerontology · doi:10.1134/s2079057024600186 · Cited by 1 · see citing works
Bentolila, G., Agrawal, N., Phung, J., Van, L. M., & Trivedi, G. (2024) · Berkeley Pharma Tech Journal of Medicine · doi:10.52243/bptjm.v4i2.71 · Cited by 1 · see citing works
Singh, A., Singh, L., & Dalal, D. (2026) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-026-05656-4 · Cited by 1 · see citing works
Yao, M., Liu, A., Xing, L., Song, J., Yang, Y., Yue, X., & Li, H. (2026) · Ageing Research Reviews · doi:10.1016/j.arr.2026.103260 · Cited by 1 · see citing works
Heinrichs, D. P., & Samsonraj, R. M. (2026) · Current Osteoporosis Reports · doi:10.1007/s11914-026-00977-y · Cited by 1 · see citing works
Potential Biomolecule Fisetin: Molecular and Pharmacological Perspectives
Kamboj, A., Kamboj, A., Malhotra, H., & Kaushik, P. (2024) · Current Materials Science · doi:10.2174/0126661454285734240311094827 · Cited by 1 · see citing works
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Pancreatic β-Cell Senescence: A Contributor to Type 2 Diabetes
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Neuroprotective Effects of Fisetin by Fighting Neuroinflammation
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Fisetin: Advances on Resources, Biosynthesis Pathway, Bioavailability, Bioactivity, and Pharmacology
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Pharmacological Interventions for Maintaining Brain Health in Ageing
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Ferroptosis vs. Ferrosenescence in Neurodegeneration and Schizophrenia
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Ferroptosis vs. Ferrosenescence in Neurodegeneration and Schizophrenia
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Microglial senescence and senolytic drugs
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- Authors
- Elsallabi, O., Patruno, A., Pesce, M., Cataldi, A., Carradori, S., & Gallorini, M.
- Affiliations
- Karolinska Institutet (SE)
- University of Chieti-Pescara (IT)
- Corresponding author
- Carradori, Simone
- ORCID
- Venue
- Molecules
- Publisher
- MDPI AG
- Published
- 2022-01-23
- Volume
- 27
- Issue
- 3
- Pages
- 738
- ISSN
- 1420-3049 (ISSN-L)
- PMC
- PMC8839434
- OpenAlex
- W4207044733
- Cited by
- 67
- References
- 100
- Citations by year
- 2026: 13 · 2025: 11 · 2024: 19 · 2023: 16 · 2022: 8
- FWCI
- 1.93
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecules (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Pharmacology › Flavonoids in Medical Research
- Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
- Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
- Keywords
- fisetin, senotherapy, cellular senescence, neuroprotection, brain aging, neuroinflammation, oxidative stress, Alzheimer's disease, flavonoids, antioxidant activity, pharmacokinetics, pharmacodynamics, toxicity, drug delivery, bioavailability, chemical stability, lifespan extension
- MeSH terms
- Animals, Antioxidants, Humans, Nervous System Diseases, Cellular Senescence, Neuroprotective Agents, Flavonols
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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