title: 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.
authors.affiliation: Division of Cardio-Cerebral Vascular and Hepatic Pharmacology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Xiangnan
authors.initials: X
authors.lastname: Zhang
authors.forename: Jiaying
authors.initials: J
authors.lastname: Wu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Dou
authors.forename: Binbin
authors.initials: B
authors.lastname: Xia
authors.forename: Weibo
authors.initials: W
authors.lastname: Rong
authors.forename: Gerald
authors.initials: G
authors.lastname: Rimbach
authors.forename: Yijia
authors.initials: Y
authors.lastname: Lou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D053978:Pentacyclic Triterpenes / Q000494:pharmacology*; D061251:Primary Cell Culture; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000633:toxicity
chemical_list: C064769:N-acetylsphingosine; D018696:Neuroprotective Agents; D053978:Pentacyclic Triterpenes; D017382:Reactive Oxygen Species; C017032:asiatic acid; D013110:Sphingosine