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

ABSTRACT

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 µmol/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 µmol/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.