Neuro-protective effects of aloperine in an Alzheimer's disease cellular model

Excessive production of amyloid beta (A beta) induced by familial mutations in amyloid precursor protein (APP) and presenilin 1 (PS1) results in neuronal oxidative insults, mitochondrial dysfunction, and apoptosis, which play an essential role in the pathological development of Alzheimer's disease (AD). Aloperine, a quinolizidine alkaloid derived from the leaves of the Sophora plant, has displayed multiple pharmacological functions in several chronic diseases. In the current study, we investigated the neuro-protective effects of aloperine against cytotoxicity in mouse Neuro2a (N2a) cells transfected with Swedish amyloid precursor protein (Swe-APP) mutant and presenilin 1 exon 9 deletion mutant (N2a/Swe.D9). We found that aloperine ameliorated oxidative stress patterns in N2a/Swe.D9 cells by reducing the production of reactive oxygen species (ROS) and 4-hydroxy-2-nonenal (4-HNE). Additionally, aloperine treatment led to elevated generation of ATP and increased mitochondrial membrane potential (MMP) in N2a/Swe.D9 cells. Importantly, we found that aloperine treatment reduced the vulnerability of N2a/Swe.D9 cells to H2O2. Aloperine also inhibited apoptosis of N2a/Swe.D9 cells via a mitochondria-dependent pathway. These findings suggest that aloperine may have pharmacological potential for the treatment of AD.