Collectively our results suggested that Fisetin may attenuate oxidative stress, neuroinflammation, neurodegeneration, and memory impairment in D-gal-treated mice via regulation of SIRT1, Nrf2/HO-1, and p-JNK/NF-kB-mediated neuroinflammation. The gene discussed is NFE2L2; the disease is memory impairment.