Neuroprotective effect of loganin against Aβ25-35- induced injury via the NF-κB-dependent signaling pathway in PC12 cells

Amyloid-beta (A beta) protein, the main constituent of senile plaques, is believed to play a pivotal role in the pathogenesis of Alzheimer's disease (AD). AD is closely associated with inflammatory reactions which are considered to be responses to A beta deposition. The present study investigated the effect of loganin on A beta(25-35)-induced inflammatory damage and the underlying molecular mechanism of its neuroprotective action. Loganin predominantly prevented A beta(25-35)-stimulated cell death through suppressing ROS generation, and attenuating apoptosis by inhibiting caspase-3 activity and regulating cell cycle. Furthermore, loganin suppressed the level of TNF-alpha and protein expression of iNOS and COX-2 in A beta(25-35)-injured PC12 cells. These inhibitions appeared to correlate with the suppression of NF-kappa B activation by loganin, as pretreating cells with loganin blocked the translocation of NF-kappa B into the nuclear compartment and degradation of the inhibitory subunit I kappa B. Loganin substantially inhibited phosphorylation of MAPKs including ERK1/2, p38 and JNK, which are closely related to regulation of NF-kappa B activation. Taken together, the results implied that loganin attenuated neuroinflammatory responses through the inactivation of NF-kappa B by NF-kappa B dependent inflammatory pathways and phosphorylation of MAPK in A beta(25-35)-induced PC12 cells.