Asiatic acid protects primary neurons against C2-ceramide-induced apoptosis

Ceramides derived from sphingosine contribute to the apoptotic processes of neuronal cells in neurodegenerative disorders including Alzheimer's disease. This study investigates the potential neuroprotective effects of Asiatic acid, a triterpenoid derived from Centella asiatica, against C-2-ceramides-induced cell death in primary cultured rat cortical neuronal cells. In primary neurons, Asiatic acid (0.01 to 1.0 mu mol/l) reduced C-2-ceramide-induced cell death and mitochondria membrane potential loss in a concentration-dependent manner. Furthermore, Asiatic acid decreased cellular production of reactive oxygen species following C-2-ceramide treatment. At a maximal concentration of 1.0 mu mol/l, Asiatic acid partly counteracted the pro-apoptotic effects of the C-2-ceramide by reducing the cytosolic release of HtrA2/Omi, the upregulation of Bax and caspase 3, as well as the dephosphorlyation of ERK1/2. Taken together, these data suggest that Asiatic acid protects neurons from C-2-ceramide-induced cell death by antagonizing mitochondria-dependent apoptosis. (C) 2012 Elsevier B.V. All rights reserved.