Fisetin

Category: flavonoid

Aliases: 3,7,3′,4′-tetrahydroxyflavone

Pharmacological Mechanism

Flavonol with senolytic activity — preferentially induces apoptosis in senescent cells via Bcl-2/Bcl-xL inhibition. Also inhibits CD38 (NAD⁺ preservation), activates Nrf2 (antioxidant response), and reduces neuroinflammation (inhibits NF-κB and microglial activation). Strongest senolytic candidate among natural flavonoids in screens (Yousefzadeh 2018).

Half-Life (t½)

PO: 3.1h

Dosing Guidelines

• PO: Typical 233 mg (Range: 100–500 mg)

Target Organ Systems

• musculoskeletal
• immune-hematologic

Interactions

• Quercetin (synergistic): Both flavonols with overlapping senolytic and CD38-inhibitory activity.

Pathways It Modulates

• Cellular senescence / SASP / senolytics (inhibitor) — mono-senolytic (PI3K/AKT + BCL pathway)
• Ferroptosis (inhibitor) — ferroptosis (senolytic + neuroprotective)
• Mitophagy (activator) — mitophagy + senolytic
• NAD+ / sirtuin / longevity axis (activator) — senolytic + SIRT1
• Nrf2 / Keap1 antioxidant response (activator) — senolytic + Nrf2

Chemical Identifiers

• PubChem CID: 5281614
• Formula: C15H10O6
• Molecular weight: 286.24 g/mol
• InChIKey: XHEFDIBZLJXQHF-UHFFFAOYSA-N
• SMILES: C1=CC(=C(C=C1C2=C(C(=O)C3=C(O2)C=C(C=C3)O)O)O)O

References

• PMID 15113710