title: Malibatol A protects against brain injury through reversing mitochondrial dysfunction in experimental stroke.
abstract: Ischemic stroke is particularly susceptible to free radicals mediated secondary neuronal damage, especially mitochondrial dysfunction. Malibatol A (MA), a novel resveratrol oligomer, has shown potential antioxidant property in vitro. But little is known about its effect on central nervous system (CNS) in vivo. In the present study, the effect of MA was evaluated in focal cerebral ischemia induced by right middle cerebral artery occlusion (MCAO) in mice. MA at the dose of 20 mg/kg was administered by caudal-vein injection within 15 min after reperfusion. At 24 h after cerebral ischemia/reperfusion (I/R) injury, ameliorated neurological scores and reduced infarct volume was observed in MA treated group. Also, MA treatment restored the increased levels of reactive oxygen species (ROS), 3-Nitrotyrosine (3-NT), and 4-Hydroxynonenal (4-HNE) induced by MCAO. The activities of respiratory enzyme complex I, III and mitochondrial transmembrane potential (Δ<PSI>m) were effectively preserved compared with MCAO group through MA treatment. Western blot analysis showed a marked increase in Bcl-2 and decrease in Bax expression after MA treatment as compared with MCAO group. Moreover, MA treatment prevented release of cytochrome c from mitochondria into cytoplasm and blunted activities of caspase-9 and caspase-3. Collectively, the present study indicates that MA can ameliorate MCAO-induced mitochondrial dysfunction, and this might partially contribute to its protective effect on brain damage after 24 h of I/R injury.
authors.affiliation: Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China; Diagnosis and Therapy Center of Stroke in Jiangsu Province, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China; Diagnosis and Therapy Center of Stroke in Jiangsu Province, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China; Diagnosis and Therapy Center of Stroke in Jiangsu Province, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Pan
authors.affiliation: Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.
authors.forename: Huiming
authors.initials: H
authors.lastname: Ge
authors.affiliation: Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China; Diagnosis and Therapy Center of Stroke in Jiangsu Province, China.
authors.forename: Kailin
authors.initials: K
authors.lastname: Yin
authors.affiliation: Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Zhengzheng
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Dujuan
authors.initials: D
authors.lastname: Sha
authors.affiliation: Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China; Diagnosis and Therapy Center of Stroke in Jiangsu Province, China; Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China; Jiangsu Key Laboratory for Molecular Medicine, Nanjing University Medical School, Nanjing, China. Electronic address: xuyun20042001@aliyun.com.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D013267:Stilbenes / Q000494:pharmacology / Q000627:therapeutic use*; D020521:Stroke / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D018696:Neuroprotective Agents; D013267:Stilbenes; C111734:malibatol A
keywords: Ischemic stroke; Malibatol A; Mitochondria; Oxidative stress