Fisetin, a flavonoid found in various fruits and vegetables such as strawberries, onions, and apples, has garnered significant attention for its array of health benefits. Some of the most notable benefits include:

1. Neuroprotective Effects:

   • Fisetin has demonstrated the ability to prevent the development and progression of several neurological disorders, such as Alzheimer's, Parkinson's, Huntington's disease, amyotrophic lateral sclerosis (ALS), stroke, and traumatic brain injury¹².
   • Its actions on multiple pathways help in reducing age-associated changes in the brain, largely due to its anti-inflammatory and antioxidant properties¹³.

2. Antioxidant Properties:

   • Fisetin is a potent antioxidant capable of scavenging free radicals, reducing oxidative stress, and mitigating lipid peroxidation and protein oxidation⁴⁵.
   • It increases the intracellular levels of antioxidants like glutathione (GSH), thus protecting cells from damage caused by reactive oxygen species (ROS)⁶.

3. Anti-Inflammatory Actions:

   • Fisetin inhibits pro-inflammatory cytokines such as TNF-α and IL-6, which makes it useful in managing inflammatory diseases like osteoarthritis⁷.
   • It also mimics anti-inflammatory and anti-oxidant enzyme activities, thereby ameliorating inflammation in various tissues⁷⁸.

4. Anti-Tumor Activity:

   • Fisetin has shown anti-tumor properties in several in vitro and in vivo studies. It inhibits the proliferation and migration of cancer cells and induces apoptosis in tumor cells⁴⁹.
   • Fisetin can inhibit the progression of cancers, such as lung and oral squamous cell carcinoma⁴.

5. Senolytic Properties:

   • This flavonoid is noted for its senolytic activity, meaning it can selectively induce the death of senescent cells, which are cells that have stopped dividing but not died¹⁰.
   • Treating aged or progeroid mice with fisetin has been shown to reduce markers of cellular senescence, restore tissue homeostasis, and extend lifespan¹⁰.

6. Anti-Diabetic Effects:

   • Fisetin exhibits anti-diabetic properties by inhibiting α-glucosidase, an enzyme responsible for breaking down carbohydrates into glucose⁴.

Overall, fisetin's broad spectrum of biological activities underscores its potential as a promising therapeutic agent for various age-related and chronic diseases.

Footnotes

1. Pamela Maher, "Preventing and Treating Neurological Disorders with the Flavonol Fisetin," NCBI, 2021. ↩ ↩²

2. Syed Shams ul Hassan, "The neuroprotective effects of fisetin, a natural flavonoid in neurodegenerative diseases: Focus on the role of oxidative stress," NCBI, 2022. ↩

3. Naghma Khan, "Fisetin: A Dietary Antioxidant for Health Promotion," NCBI, 2012. ↩

4. Suhyeon Park, "Effects of Fisetin, a Plant-Derived Flavonoid, on Response to Oxidative Stress, Aging, and Age-Related Diseases in Caenorhabditis elegans," NCBI, 2022. ↩ ↩² ↩³ ↩⁴

5. Grzegorz Grynkiewicz, "New Perspectives for Fisetin," NCBI, 2019. ↩

6. Naghma Khan, "Fisetin is a senotherapeutic that extends health and lifespan," NCBI, 2018. ↩

7. Zahra Nabizadeh, "Evaluation of the anti-inflammatory activity of fisetin-loaded nanoparticles in an in vitro model of osteoarthritis," NCBI, 2023. ↩ ↩²

8. Joanna Szymczak, "Fisetin—In Search of Better Bioavailability—From Macro to Nano Modifications: A Review," NCBI, 2023. ↩

9. Sophia A. Mahoney, "Intermittent supplementation with fisetin improves arterial function in old mice by decreasing cellular senescence," NCBI, 2023. ↩

10. Matthew J Yousefzadeh, "Fisetin is a senotherapeutic that extends health and lifespan," PubMed, 2018. ↩ ↩²