title: Protective effects of nigranoic acid on cerebral ischemia-reperfusion injury and its mechanism involving apoptotic signaling pathway.
abstract: The goal of this study was to assess the expression of poly ADP-ribose polymerase (PARP) and apoptosis-inducing factor (AIF) in the hippocampal CA1 region, and to find out whether nigranoic acid treatment exhibits protective effects on brain through PARP/AIF signaling pathway in cerebral ischemia-reperfusion animal model. Rats were randomly divided into three groups: Sham-surgery, ischemia-reperfusion, and nigranoic acid-treated. Rat models of middle cerebral artery occlusion were prepared using a way of thread occlusion. Rats in the nigranoic acid group were administered with 1 mg/kg intragastric nigranoic acid 6 and 2 h before brain ischemia, respectively. Following reperfusion, samples were collected at different time-points (6, 24, and 72 h) and each group was further divided into three subgroups. Apoptosis was measured using the terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling method. The protein expression levels of AIF and PARP were detected using Western blot and AIF mRNA quantity was evaluated using the reverse transcription-polymerase chain reaction. Apoptosis, levels of AIF and PARP protein expression, and levels of AIF mRNA expression were significantly increased in the ischemia-reperfusion group compared with the sham-surgery group. However, apoptosis and the expression levels of AIF protein, PARP protein, and AIF mRNA at different time-points were significantly decreased in the nigranoic acid-treated group compared with the model group. We can judge that nigranoic acid has a strong protective effect on rat cerebral ischemia-reperfusion injury, and acts by downregulating nerve cell apoptosis by preventing the overactivation of PARP and AIF nuclear translocation.
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, People's Republic of China, drtiandafeng@163.com.
authors.forename: Tianda
authors.initials: T
authors.lastname: Feng
authors.forename: Yunhui
authors.initials: Y
authors.lastname: Liu
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000235:genetics / Q000378:metabolism; D002545:Brain Ischemia / Q000150:complications*; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects*; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D051033:Apoptosis Inducing Factor; D012333:RNA, Messenger; D014315:Triterpenes; C100860:nigranoic acid; D011065:Poly(ADP-ribose) Polymerases