Synergistic neuroprotective effect of schisandrin and nootkatone on regulating inflammation, apoptosis and autophagy via the PI3K/AKT pathway

Alzheimer's disease (AD) is a neurodegenerative disease that seriously threatens elderly health. Schisandrin (SCH) and nootkatone (NKT) are two core components derived from Alpinia oxyphylla-Schisandra chinensis herb pair (ASHP), a traditional Chinese medicine formulation. Previous studies demonstrated that the combination of NKT and SCH exerted a neuroprotective effect in AD mouse models. The present study was undertaken to investigate whether there was a synergistic effect between NKT and SCH and the possible mechanism in Aβ1-42 induced PC12 cells. SCH (50 μM) and NKT (10 μM) had the most notable inhibitory effect on the level of Aβ secreted by cells. Treatment with NKT + SCH activated the PI3K/AKT/Gsk-3β/mTOR pathway. Inflammation related proteins such as NF-κB, IKK, IL-1β, IL-6 and TNF-α were decreased. The levels of cleaved-Caspase3 and LC3-II were reduced, indicating that apoptosis and autophagy were inhibited. These results revealed that NKT + SCH exerted a neuroprotective effect via the PI3K/AKT pathway, inhibiting inflammation, apoptosis and autophagy.