Abstract
Berberine plays a neuroprotective role in neurodegenerative disorders, including Alzheimer's disease (AD). However, the underlying mechanism by which berberine inhibits AD progression remains largely unclear. The AD model was established using PC12 cells after treatment of amyloid beta (Aβ)25-35. Cells were transfected with microRNA (miRNA)-107 mimic, inhibitor, zinc finger protein 217 (ZNF217) overexpression or corresponding negative controls. Cell viability, apoptosis and inflammatory cytokine secretion were measured by MTT, flow cytometry or enzyme linked immunosorbent assay, respectively. The expressions of miR-107, ZNF217 and phosphorylated tau (p-Tau) were detected by quantitative real-time polymerase chain reaction or Western blot. The association between miR-107 and ZNF217 was explored by luciferase reporter assay and RNA immunoprecipitation. Berberine attenuated Aβ25-35-induced viability suppression in PC12 cells. Moreover, berberine inhibited the Aβ25-35-induced increase of inflammatory cytokine expression, apoptosis and p-Tau level in PC12 cells. miR-107 expression was reduced in Aβ25-35-treated PC12 cells and its overexpression alleviated Aβ25-35-induced injury, which was further weakened by combination with berberine. ZNF217 was a target of miR-107 and its addition reversed miR-107-mediated inhibition of inflammatory injury, apoptosis and phosphorylation of tau. Besides, ZNF217 protein level was decreased by berberine via regulating miR-107 in Aβ25-35-treated PC12 cells. Berberine protected against Aβ25-35-induced inflammatory injury, apoptosis and phosphorylation of tau by regulating miR-107 and ZNF217, indicating berberine as a promising neuroprotective agent for therapeutics of AD.