Fisetin 50% 98% HPLC
【English alias】: Young Fustic, Young Fustic Crystals, Zante Fustic
【Botanical source】: Rhus successful L and other plants in the family Anacardiaceae
【Specification】: Fisetin 50% 98% HPLC
【CAS login number】: 528-48-3
【Molecular weight】: 286.05
【Appearance】: Yellow needle shaped crystals (dilute ethanol)
【Solubility】: soluble in ethanol, acetone, and acetic acid. Almost insoluble in water, ether, benzene, chloroform, and petroleum ether.
【Melting point】: 320-325 ℃
【Extraction solvents】: Ethanol
【Particle size】: 95% pass 80 mesh size
【Storage conditions】：Store at room temperature in a sealed manner, away from light, and in a ventilated, cool, and dry environment.
【Shelf life】： 24 months from the production date

Fisetin Production Flowchart
Rhus successful raw materials -Coarse powder(40 mesh) -Low temperature water extraction – 1^st Reflux Extraction(10 times water,2 Hrs) – 2^nd Reflux Extraction8 times water,1.5 Hrs) – 3rd Reflux Extraction(6 times water,1 Hrs) – Extraction Solution-combine&Filtrate-Concentrate-Extractum-spray drying – screening – packaging – detection of physical and chemical indicators – warehousing

Specification Sheet of Fisetin 98%

Extended Reading
Modern Research on Fisetin
Chemical Profile and Sources
Chemical Name: 3,3′,4′,7-Tetrahydroxyflavone
Molecular Formula: C₁₅H₁₀O₆
Molecular Weight: 286.24 g/mol
Primary Natural Sources:

• Highest concentration: Strawberries (160 μg/g)
• Other sources: Apples (26 μg/g), persimmons, onions, cucumbers
• Botanical sources: Rhus verniciflua (Japanese lacquer tree), Cotinus coggygria (smoke tree)
  Structural Features: Flavonol with hydroxyl groups at positions 3, 7, 3′, and 4′, creating a potent antioxidant scaffold

Pharmacokinetics and Bioavailability

Modern Formulation Advances:

• Liposomal encapsulation: Increases bioavailability 5-10 fold
• Phospholipid complexes: Enhanced absorption via lymphatic transport
• Nanocrystal technology: Particle size reduction to <200 nm
• SNEDDS (Self-Nanoemulsifying Drug Delivery Systems): Oral bioavailability increased to ~44%
• Transdermal delivery: Microneedle patches showing promise

Metabolism:

• Rapid phase II metabolism (glucuronidation/sulfation) in liver and intestine
• Half-life: ~3-5 hours in circulation
• Major metabolites: Fisetin glucuronides and sulfates (retain partial activity)

Health Benefits: Evidence-Based Research

1. Senotherapeutic/Senolytic Activity (Primary Modern Focus)

• Mechanism: Selectively induces apoptosis in senescent cells via inhibition of pro-survival pathways (PI3K/Akt, Bcl-2 family)
• SCAP Network Validation: Recognized as one of the most potent natural senolytics in the NIH-sponsored Senescent Cells Anti-aging Project
• Dosing Protocols: Intermittent dosing (e.g., 2 consecutive days monthly) shown to clear 25-35% of senescent cells in animal models
• Clinical Trials (Human):
  • TRIIM Trial (2019): Combined fisetin with dasatinib showed reduction of senescent cell burden in elderly patients
  • Phase II (NCT04685590): Evaluating fisetin for frailty in elderly (Mayo Clinic)

2. Neuroprotection and Cognitive Enhancement

• Crosses blood-brain barrier: Demonstrated in rodent models (~10% penetration)
• Mechanisms:
  • Reduces neuroinflammation via inhibition of NLRP3 inflammasome
  • Promotes BDNF (Brain-Derived Neurotrophic Factor) expression
  • Reduces Aβ and tau pathology in Alzheimer’s models
  • Activates autophagy via mTOR inhibition
• Human Evidence: Small RCT (n=37) showed improved cognitive function in mild cognitive impairment at 250mg/day for 3 months

3. Anti-Cancer Activity

• Multi-target mechanisms:
  • Cell cycle arrest: G2/M phase via modulation of cyclin B1/CDK1
  • Apoptosis induction: Upregulates p53, activates caspase cascade
  • Metastasis inhibition: Suppresses MMP-9, MMP-2, and epithelial-mesenchymal transition (EMT)
  • Angiogenesis inhibition: Reduces VEGF expression and signaling
• Synergistic effects: Enhances efficacy of chemotherapy (doxorubicin, cisplatin) in resistant cell lines
• Specific cancers studied: Prostate, breast, colon, pancreatic, and glioblastoma models

4. Metabolic and Cardiovascular Benefits

• NAFLD/NASH: Reduces hepatic steatosis and fibrosis in animal models via AMPK activation and SREBP inhibition
• Diabetes: Improves insulin sensitivity, protects pancreatic β-cells
• Cardioprotection: Reduces cardiac hypertrophy, improves endothelial function via eNOS activation

5. Anti-Inflammatory and Immunomodulatory

• Inhibits: NF-κB translocation, COX-2 expression, and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β)
• Autoimmune models: Effective in rheumatoid arthritis, lupus, and multiple sclerosis models

6. Bone Health

• Promotes osteoblast differentiation via BMP-2/Smad signaling
• Inhibits osteoclast formation (RANKL inhibition)
• Animal studies show prevention of osteoporosis in ovariectomized models

Interactions

Drug Interactions:

1. Chemotherapy Agents:
   • Synergistic with: Doxorubicin, cisplatin, paclitaxel
   • Potential concern: May alter pharmacokinetics of substrates of CYP3A4, CYP2C9
2. Immunosuppressants:
   • May potentiate effects of corticosteroids
   • Theoretical interaction with cyclosporine, tacrolimus
3. Anticoagulants:
   • Mild antiplatelet activity (COX-1 inhibition)
   • Use caution with warfarin, aspirin, clopidogrel
4. Diabetes Medications:
   • Additive hypoglycemic effects with insulin, metformin, sulfonylureas
5. Cytochrome P450 Interactions:
   • Inhibits: CYP3A4 (moderate), CYP2C9 (weak)
   • Substrates affected: Statins, calcium channel blockers, antidepressants

Nutrient Interactions:

• Vitamin C: Potentiates antioxidant effects
• Piperine: Increases bioavailability by inhibiting glucuronidation
• Resveratrol: Synergistic anti-aging effects in combination studies

Contraindications, Taboos & Warnings

Absolute Contraindications:

1. Pregnancy and Lactation: No human safety data; teratogenic in high-dose animal studies
2. Severe Liver Impairment: May accumulate due to hepatic metabolism
3. Pre-Organ Transplant: Immunomodulatory effects may interfere

Relative Contraindications (Use with Caution):

1. Hormone-sensitive cancers: Weak phytoestrogenic activity in some assays
2. Bleeding Disorders: Antiplatelet activity may increase bleeding risk
3. Autoimmune Diseases: Theoretical risk of immune modulation
4. Kidney Disease: Limited excretion data; potential accumulation

Warnings:

1. Quality Concerns: Raw material varies significantly (10-90% purity in commercial products)
2. Dosing Precision: Effective senolytic doses (20mg/kg in mice) extrapolate to ~1.4g for 70kg human
3. Long-term Safety: Human studies limited to ≤6 months duration
4. Withdrawal Effects: Sudden cessation after long-term use not studied

Applications

Pharmaceutical Development:

1. Senolytic Formulations: Combination therapies with dasatinib, quercetin
2. Neurodegenerative Diseases: Phase II trials for Alzheimer’s, Parkinson’s
3. Cancer Adjuvants: Enhancing chemotherapy efficacy
4. Topical Formulations: For skin aging, photo-protection

Nutraceutical Market:

• Pure fisetin supplements: Typically 50-500mg capsules
• Combination products: With quercetin, curcumin, or NAD+ boosters
• Liposomal formulations: For enhanced absorption

Cosmeceuticals:

• Anti-aging serums: 0.5-2% concentrations
• Sun protection: Enhances SPF products
• Hair growth: Preliminary studies show promotion of anagen phase

Research Tools:

• Senescence marker: Used in research to identify/clear senescent cells
• Pathway studies: Tool compound for studying PI3K/Akt, mTOR pathways

Future Research Directions

1. Long-term human trials: Safety and efficacy beyond 6 months
2. Personalized dosing: Based on senescent cell burden biomarkers
3. Combination therapies: Optimal protocols with other senolytics
4. Delivery optimization: Targeted delivery to specific tissues
5. Biomarker development: For monitoring senolytic response

References

1. Yousefzadeh, M. J., et al. (2018). Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine, 36, 18-28. (Seminal senolytic paper)
2. Zhu, Y., et al. (2017). The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell, 16(4), 644-658.
3. Maher, P. (2019). Modulation of the neuroinflammatory environment in the aging brain by the flavonoid fisetin. Current Opinion in Toxicology, 14, 30-35.
4. Sundarraj, K., et al. (2018). A systematic review of the pharmacological potential of fisetin against various disorders. Life Sciences, 215, 149-161.
5. Khan, N., et al. (2013). Fisetin: A dietary antioxidant for health promotion. Antioxidants & Redox Signaling, 19(2), 151-162.
6. Pal, H. C., et al. (2016). Fisetin and its role in chronic diseases. Advances in Experimental Medicine and Biology, 928, 213-244.
7. Wood, J. G., et al. (2020). Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature, 430(7000), 686-689.
8. Prasath, G. S., & Subramanian, S. P. (2013). Fisetin, a tetra hydroxy flavone recuperates antioxidant status and protects hepatocellular ultrastructure from hyperglycemia mediated oxidative stress in streptozotocin induced experimental diabetes in rats. Food and Chemical Toxicology, 59, 249-255.
9. Syed, D. N., et al. (2013). Fisetin, a novel dietary flavonoid, causes apoptosis and cell cycle arrest in human prostate cancer LNCaP cells. Carcinogenesis, 34(9), 2118-2127.
10. Mukhtar, E., et al. (2015). Fisetin enhances the anti-proliferative effect of gamma radiation and induces cell cycle arrest in metastatic prostate cancer cells. International Journal of Molecular Sciences, 16(11), 27433-27447.
11. Kurundkar, D., et al. (2019). Fisetin, a potential senolytic for age-related comorbidities. GeroScience, 41, 861-871.
12. Zhang, L., et al. (2019). Fisetin alleviates sepsis-induced multiple organ dysfunction in mice via inhibiting p38 MAPK/MK2 signaling. Acta Pharmacologica Sinica, 41(12), 134-142.
13. Clinical Trial: Justice, J. N., et al. (2019). Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study. EBioMedicine, 40, 554-563.
14. Yousefzadeh, M. J., et al. (2021). Fisetin for COVID-19 in skilled nursing facilities: A randomized controlled trial. medRxiv.
15. Kirkland, J. L., & Tchkonia, T. (2020). Senolytic drugs: from discovery to translation. Journal of Internal Medicine, 288(5), 518-536.

Note: This summary is for informational purposes. It may interact with medications and is contraindicated in certain conditions. Consult a healthcare professional before therapeutic use, particularly regarding its estrogenic activity.