title: Asiatic acid, a pentacyclic triterpene in Centella asiatica, attenuates glutamate-induced cognitive deficits in mice and apoptosis in SH-SY5Y cells.
abstract: OBJECTIVE
  To investigate whether asiatic acid (AA), a pentacyclic triterpene in Centella asiatica, exerted neuroprotective effects in vitro and in vivo, and to determine the underlying mechanisms.
  
  
  METHODS
  Human neuroblastoma SH-SY5Y cells were used for in vitro study. Cell viability was determined with the MTT assay. Hoechst 33342 staining and flow cytometry were used to examine the apoptosis. The mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) were measured using fluorescent dye. PGC-1α and Sirt1 levels were examined using Western blotting. Neonatal mice were given monosodium glutamate (2.5 mg/g) subcutaneously at the neck from postnatal day (PD) 7 to 13, and orally administered with AA on PD 14 daily for 30 d. The learning and memory of the mice were evaluated with the Morris water maze test. HE staining was used to analyze the pyramidal layer structure in the CA1 and CA3 regions.
  
  
  RESULTS
  Pretreatment of SH-SY5Y cells with AA (0.1-100 nmol/L) attenuated toxicity induced by 10 mmol/L glutamate in a concentration-dependent manner. AA 10 nmol/L significantly decreased apoptotic cell death and reduced reactive oxygen species (ROS), stabilized the mitochondrial membrane potential (MMP), and promoted the expression of PGC-1α and Sirt1. In the mice models, oral administration of AA (100 mg/kg) significantly attenuated cognitive deficits in the Morris water maze test, and restored lipid peroxidation and glutathione and the activity of SOD in the hippocampus and cortex to the control levels. AA (50 and 100 mg/kg) also attenuated neuronal damage of the pyramidal layer in the CA1 and CA3 regions.
  
  
  CONCLUSIONS
  AA attenuates glutamate-induced cognitive deficits of mice and protects SH-SY5Y cells against glutamate-induced apoptosis in vitro.
authors.affiliation: School of Pharmacy, Jiangsu University, Zhenjiang, China.
authors.forename: Min-fang
authors.initials: MF
authors.lastname: Xu
authors.forename: Yu-yun
authors.initials: YY
authors.lastname: Xiong
authors.forename: Jian-kang
authors.initials: JK
authors.lastname: Liu
authors.forename: Jin-jun
authors.initials: JJ
authors.lastname: Qian
authors.forename: Li
authors.initials: L
authors.lastname: Zhu
authors.forename: Jing
authors.initials: J
authors.lastname: Gao
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D015153:Blotting, Western; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D056654:CA3 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D028041:Centella / Q000737:chemistry; D003071:Cognition / Q000187:drug effects*; D003704:Dementia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control* / Q000523:psychology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005978:Glutathione / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology*; D018696:Neuroprotective Agents / Q000302:isolation & purification / Q000494:pharmacology*; D018697:Nootropic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D053978:Pentacyclic Triterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D056564:Sirtuin 1 / Q000378:metabolism; D012970:Sodium Glutamate; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D006360:Heat-Shock Proteins; D018696:Neuroprotective Agents; D018697:Nootropic Agents; C486497:PPARGC1A protein, human; D053978:Pentacyclic Triterpenes; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors; C017032:asiatic acid; D013482:Superoxide Dismutase; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D005978:Glutathione; D012970:Sodium Glutamate