Promote senolytic activities by upregulating the expression of sirtuin 1 (SIRT1) with fisetin. As a histone deacetylase (HDAC), SIRT1 helps inhibit many transcription factors, such as p53, nuclear factor kappa B (NF-κB), and forkhead box O (FOXO) (Ayissi et al.). Fisetin inhibits DNA methyltransferase 1 (DNMT1)-mediated DNA methylation (IC50 = 3.5 μM) through direct inhibition of the DNA methylase, which can lead to multiple effects on gene silencing (Lee et al.).
Fisetin has been used for:
MAINTENANCE AND SELF-RENEWAL
· Enhances survival of PC12 cells from tunicamycin (Tm)-mediated cell death by mitigating apoptosis, autophagy, and reactive oxygen species (ROS) production (Yen et al.).
IMMUNOLOGY
· Downregulates phorbol-12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated gene expression and production of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-4, IL-6, and IL-8 in human mast cells (Park et al.).
CANCER RESEARCH
· Inhibits the PI3K/Akt and mTOR pathway in prostate, lung, myeloma, and melanoma cancer cells (Adhami et al.; Syed et al.).
· Known to possess antioxidant activity. Mechanistically, fisetin has been shown to attenuate H2O2-induced cell damage by scavenging ROS and activating GSH pathways in vitro (Kang et al.; Zhang et al.)
DISEASE MODELING
· Induces ERK activation which provides neuroprotective activities in Huntington’s disease models (Maher et al.).
· Reduces senescence and age-related pathologies in yeast, simple eukaryotes, and mice (Grynkiewicz and Demchuk; Wood et al.; Yousefzadeh et al.).
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