title: Beneficial effect of astragalosides on stroke condition using PC12 cells under oxygen glucose deprivation and reperfusion.
abstract: Astragalosides (AST) are reported to be neuroprotective in focal cerebral ischemic models in vivo. In this study, the direct effect of AST against oxygen and glucose deprivation (OGD) including neuronal injury and the underlying mechanisms in vitro were investigated. 5 h OGD followed by 24 h of reperfusion [adding back oxygen and glucose (OGD-R)] was used to induce in vitro ischemia reperfusion injury in differentiated rat pheochromocytoma PC12 cells. AST (1, 100, and 200 µg/mL) were added to the culture after 5 h of the OGD ischemic insult and was present during the reoxygenation phases. A key finding was that OGD-R decreased cell viability, increased lactate dehydrogenase, increased reactive oxygen species, apoptosis, autophagy, functional impairment of mitochondria, and endoplasmic reticulum stress in PC12 cells, all of which AST treatment significantly reduced. In addition, AST attenuated OGD-R-induced cell loss through P38 MAPK activation a neuroprotective effect blunted by SB203580, a specific inhibitor of P38 MAPK. Our data suggest that both apoptosis and autophagy are important characteristics of OGD-R-induced PC12 death and that treating PC12 cells with AST blocked OGD-R-induced apoptosis and autophagy by suppressing intracellular oxidative stress, functional impairment of mitochondria, and endoplasmic reticulum stress. Our data provide identification of AST that can concomitantly inhibit multiple cells death pathways following OGD injuries in neural cells.
authors.affiliation: Department of Chinese Medicine, Chi Mei Medical Center, Tainan, 710, Taiwan, Republic of China.
authors.forename: Bi-Ying
authors.initials: BY
authors.lastname: Chiu
authors.forename: Ching-Ping
authors.initials: CP
authors.lastname: Chang
authors.forename: Jia-Wei
authors.initials: JW
authors.lastname: Lin
authors.forename: Jung-Sheng
authors.initials: JS
authors.lastname: Yu
authors.forename: Wen-Pin
authors.initials: WP
authors.lastname: Liu
authors.forename: Yao-Chin
authors.initials: YC
authors.lastname: Hsu
authors.forename: Mao-Tsun
authors.initials: MT
authors.lastname: Lin
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D015427:Reperfusion Injury; D012503:Saponins / Q000494:pharmacology*; D020521:Stroke / Q000188:drug therapy*; D014315:Triterpenes / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D012503:Saponins; D014315:Triterpenes; C052064:astragaloside A; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose; D010100:Oxygen