title: Taxifolin ameliorates cerebral ischemia-reperfusion injury in rats through its anti-oxidative effect and modulation of NF-kappa B activation.
abstract: Infarction in adult rat brain was induced by middle cerebral arterial occlusion (MCAO) followed by reperfusion to examine whether taxifolin could reduce cerebral ischemic reperfusion (CI/R) injury. Taxifolin administration (0.1 and 1.0 microg/kg, i.v.) 60 min after MCAO ameliorated infarction (by 42%+/-7% and 62%+/-6%, respectively), which was accompanied by a dramatic reduction in malondialdehyde and nitrotyrosine adduct formation, two markers for oxidative tissue damage. Overproduction of reactive oxygen species (ROS) and nitric oxide (NO) via oxidative enzymes (e.g., COX-2 and iNOS) was responsible for this oxidative damage. Taxifolin inhibited leukocyte infiltration, and COX-2 and iNOS expressions in CI/R-injured brain. Taxifolin also prevented Mac-1 and ICAM-1 expression, two key counter-receptors involved in firm adhesion/transmigration of leukocytes to the endothelium, which partially accounted for the limited leukocyte infiltration. ROS, generated by leukocytes and microglial cells, activated nuclear factor-kappa B (NF-kappaB) that in turn signaled up-regulation of inflammatory proteins. NF-kappaB activity in CI/R was enhanced 2.5-fold over that of sham group and was inhibited by taxifolin. Production of both ROS and NO by leukocytes and microglial cells was significantly antagonized by taxifolin. These data suggest that amelioration of CI/R injury by taxifolin may be attributed to its anti-oxidative effect, which in turn modulates NF-kappaB activation that mediates CI/R injury.
authors.affiliation: Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yea-Hwey
authors.initials: YH
authors.lastname: Wang
authors.forename: Wen-Yen
authors.initials: WY
authors.lastname: Wang
authors.forename: Chia-Che
authors.initials: CC
authors.lastname: Chang
authors.forename: Kuo-Tong
authors.initials: KT
authors.lastname: Liou
authors.forename: Yen-Jen
authors.initials: YJ
authors.lastname: Sung
authors.forename: Jyh-Fei
authors.initials: JF
authors.lastname: Liao
authors.forename: Chieh-Fu
authors.initials: CF
authors.lastname: Chen
authors.forename: Shiou
authors.initials: S
authors.lastname: Chang
authors.forename: Yu-Chang
authors.initials: YC
authors.lastname: Hou
authors.forename: Yueh-Ching
authors.initials: YC
authors.lastname: Chou
authors.forename: Yuh-Chiang
authors.initials: YC
authors.lastname: Shen
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D044948:Flavonols / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000378:metabolism; D015394:Molecular Structure; D016328:NF-kappa B / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011794:Quercetin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D051381:Rats; D020318:Rats, Long-Evans; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D044948:Flavonols; D016177:Macrophage-1 Antigen; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; D011794:Quercetin; C003377:taxifolin; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2