Luteolin Reduces Bace1 Expression Through Nf-Kappa B And Estrogen Receptor Mediated Pathways In Hek293 And Sh-Sy5y Cells

Beta-secretase (BACE1) controls an essential step for the generation of amyloid-beta peptide (A beta). As A beta forms the principle pathologies in Alzheimer's disease, lowering A beta production by inhibiting BACE1 is a plausible therapeutic approach. In the present study, we identified a natural polyphenol, luteolin, as a potent inhibitor of BACE1 transcription in human embryonic kidney 293 (HEK293) and human neuroblastoma (SH-SY5Y) cell lines. Luteolin is capable of suppressing the activation of BACE1 promoter by NF-kappa B signaling. We further characterized that luteolin interferes with NF-kappa B signaling by both directly and indirectly disrupting p65 complex formation. In addition, we discovered that estrogen receptor mediates luteolin's effect in inhibiting NF-kappa B signaling and BACE1 transcription. Interestingly, the beneficial effects of luteolin may be attributed to selective activation profiles of luteolin to different estrogen receptor subtypes. Our study reports luteolin as a potent BACE1-inhibiting compound, providing useful information in understanding estrogen receptor-and NF-kappa B-mediated signaling in regulating BACE1 expression.