Overblog Suivre ce blog
Editer l'article Administration Créer mon blog
6 mai 2012 7 06 /05 /mai /2012 08:35
Asiatic acid, a pentacyclic triterpene in Centella asiatica, attenuates glutamate-induced cognitive deficits in mice and apoptosis in SH-SY5Y cells Abstract Aim: 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. Conclusion: AA attenuates glutamate-induced cognitive deficits of mice and protects SH-SY5Y cells against glutamate-induced apoptosis in vitro. Min-fang Xu1, Yu-yun Xiong2, Jian-kang Liu3, Jin-jun Qian4, Li Zhu5 and Jing Gao1 1School of Pharmacy, Jiangsu University, Zhenjiang 212013, China 2School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang 212013, China 3Institute of Mitochondrial Biology & Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Xi'an Jiaotong University School of Life Science and Technology, Xi'an 710049, China 4Department of Neurology, The Forth Affiliated Hospital of Jiangsu University, Zhenjiang 212001, China 5Department of Neurobiology and Neurochemistry, Institute for Nautical Medicine and Jiangsu Key Laboratory of Neurogeneration, Nantong University, Nantong 226001, China Correspondence: Jing Gao, jinggao@ujs.edu.cn Received 13 September 2011; Accepted 10 January 2012 Advance online publication 26 March 2012 Acta Pharmacologica Sinica (2012) 33: 578–587; doi: 10.1038/aps.2012.3; published online 26 Mar 2012 Acta Pharmacologica SinicaISSN: 1671-4083EISSN: 1745-7254© 2012 Shanghai Institute of Materia Medica, CAS

Partager cet article

Repost 0
Published by Chronimed - dans Concept
commenter cet article