Protective effect of (−)clausenamide against Aβ-induced neurotoxicity in differentiated PC12 cells

The neurotoxicity of aggregated β-amyloid (Aβ) has been implicated as a critical cause in the pathogenesis of Alzheimer's disease (AD). In the present study, we investigated the effect of (−)clausenamide ((−)Clau), an aqueous extract of leaves of Clausena lassium (lour) skeel, on the neurotoxicity of Aβ25–35. The viability of differentiated PC12 cells was determined by MTT assay. Apoptosis was detected by flow cytometry. DCFH-DA was used for assessment of intracellular ROS generation, JC-1 and Rhodamine 123 for measurement of mitochondrial transmembrane potential (MMP). The intracellular calcium was determined with Fluo-3. The phosphorylation of p38 MAPK and the expression of Bcl-2, Bax, P53, Caspase 3 were examined by Western blot. The results showed that (−)Clau significantly elevated cell viability. Furthermore, (−)Clau arrested the apoptotic cascade by reversing overload of calcium, preventing ROS generation, moderated the dissipation of MMP and the misbalance of Bcl-2 and Bax, inhibiting the activation of p38 MAPK and the expression of P53 and cleaved Caspase 3. Our results suggested that (−)Clau may be a therapeutic agent for AD.