title: Oral administration of Crataegus flavonoids protects against ischemia/reperfusion brain damage in gerbils.
abstract: Stroke is the third leading cause of death as dementia is a main symptom of Alzheimer's disease. One of the important mechanisms in the pathogeny of stroke is free radical production during the reperfusion period, therefore the effects of a type of natural antioxidant, i.e. Crataegus flavonoids (CF), on brain ischemic insults were investigated in Mongolian gerbil stroke model. Results showed that pretreatment of the animals with CF decreased reactive oxygen species (ROS) production, thiobarbituric acid reactive substances content, and nitrite/nitrate concentration in brain homogenate, increased the brain homogenate-associated antioxidant level in a dose-dependent manner. CF pretreatment increased the amount of biologically available NO by scavenging of superoxide anion produced during reperfusion. At same time, in the process of ischemia/reperfusion brain damage, the content of nitrite/nitrate (the end product of NO) increased, and of NO detected by ESR decreased. Oral pretreatment with CF decreased the nitrite/nitrate content in the brain homogenate and increased the biologically available NO concentration in a dose-dependent manner. The increasing effect of antioxidant on NO might be due to its scavenging effect on superoxide anion, which could react with NO into peroxynitrite. iNOS was implied in delayed neuron death after brain ischemic damage and it was found that pretreatment with CF could decrease the protein level of tumor necrosis factor (TNF)-alpha and nuclear factor-kappa B (NF-kappaB), and increase the mRNA level of NOS estimated by western blotting and RT-PCR. More neurons survived and fewer cells suffered apoptosis in the hippocampal CA1 region of CF treated animal brain. These results suggest that oral administration of this antioxidant increases the antioxidant level in the brain and protects the brain against delayed cell death caused by ischemia/reperfusion injury.
authors.affiliation: Laboratory of Visual Information Processing, Center for Brain and Cognitive Sciences, Institute of Biophysics, Academia Sinica, Beijing, China.
authors.forename: De-Liang
authors.initials: DL
authors.lastname: Zhang
authors.forename: Yue-Ting
authors.initials: YT
authors.lastname: Zhang
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Yin
authors.forename: Bao-Lu
authors.initials: BL
authors.lastname: Zhao
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000032:analysis / Q000494:pharmacology; D001923:Brain Chemistry; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D027825:Crataegus; D004249:DNA Damage; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology*; D005609:Free Radicals / Q000032:analysis; D005849:Gerbillinae; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D009566:Nitrates / Q000032:analysis; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000032:analysis; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000473:pathology / Q000648:ultrastructure; D012333:RNA, Messenger / Q000378:metabolism; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000975:Antioxidants; D005419:Flavonoids; D005609:Free Radicals; D016328:NF-kappa B; D018696:Neuroprotective Agents; D009566:Nitrates; D009573:Nitrites; D010936:Plant Extracts; D012333:RNA, Messenger; D017392:Thiobarbituric Acid Reactive Substances; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II