Fisetin

Fisetin is a natural flavonol found in many fruits and vegetables with various benefits, such as antioxidant, anticancer, neuroprotection effects. IC50 & Target:Sirtuin, PPAR, TNF-alpha^[1][2] In Vitro: Fisetin inhibits lipid accumulation and suppresses the expression of PPARγ in 3T3-L1 cells. Fisetin suppresses early stages of preadipocyte differentiation, and induces expression of Sirt1. Fisetin facilitates Sirt1-mediated deacetylation of PPARγ and FoxO1, and enhances the association of Sirt1 with the PPARγ promoter, leading to suppression of PPARγ transcriptional activity, thereby repressing adipogenesis^[1]. Fisetin binds to tubulin and stabilizes microtubules with binding characteristics far superior than paclitaxel. Fisetin treatment of human prostate cancer cells results in robust up-regulation of microtubule associated proteins (MAP)-2 and -4. Fisetin significantly inhibits PCa cell proliferation, migration, and invasion. Nudc, a protein associated with microtubule motor dynein/dynactin complex that regulates microtubule dynamics, is inhibited with Fisetin treatment^[2]. In Vivo: Fisetin treatment to UVB exposed mice results in decreased hyperplasia and reduces infiltration of inflammatory cells. Fisetin treatment also reduces inflammatory mediators such as COX-2, PGE2 as well as its receptors (EP1- EP4), and MPO activity. Furthermore, Fisetin reduces the level of inflammatory cytokines TNFα, IL-1β and IL-6 in UVB exposed skin. Fisetin treatment also reduces cell proliferation markers as well as DNA damage as evidenced by increased expression of p53 and p21 proteins^[3].