title: Neuroprotection of hydroxysafflor yellow A in the transient focal ischemia: inhibition of protein oxidation/nitration, 12/15-lipoxygenase and blood-brain barrier disruption.
abstract: Hydroxysafflor yellow A (HSYA) is the main component of the safflower yellow pigments, the aqueous extract of safflower florets. We report here an experimental study for evaluating HSYA for their neuroprotective qualities on rats subjected to middle cerebral artery occlusion (60 min) and reperfusion (24h), an experimental model in which excessive production of reactive oxygen and nitrogen species has been found. In our data, biochemical analysis of tissue proteins showed that cerebral ischemia/reperfusion (I/R) injury resulted in significant elevation of carbonyl groups and nitrotyrosine in the brain of I/R in comparison to sham controls, indicating the occurrence of oxidative/nitrative modification to brain proteins. HSYA-treatment (1, 5 and 10mg/kg) inhibited I/R-induced protein oxidation and nitration. 12/15-Lipoxygenase (12/15-LOX), the enzyme implicated in oxidative stress of cerebral I/R, displayed overexpression in I/R rats. Elevated 12/15-LOX activity, estimated by the level of its metabolite 15-hydroxyeicosatetraenoic acid (15-HETE), was also induced by the challenge of cerebral I/R. Administration of HSYA 1, 5 and 10mg/kg reduced the upregulation of 12/15-LOX expression and activity in a dose-dependent manner. Moreover, the increase in blood-brain barrier (BBB) permeability evaluated by IgG leakage, Evans blue extravasation, and brain water content, respectively, was markedly alleviated by HSYA, indicating its protection against BBB disruption and brain edema following I/R insult. Taken together, these results demonstrate the neuroprotective properties of HSYA, which may be at least in part due to its potential to reduce protein oxidation and nitration, inhibit the upregulation of 12/15-LOX, and attenuate BBB breakdown.
authors.affiliation: Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Tianjin Medical University General Hospital, Tianjin Neurological Institute, 154 Anshan Road Heping District, Tianjin 300052, PR China. sunli_2000@hotmail.com
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Yan-Wei
authors.initials: YW
authors.lastname: Xu
authors.forename: Hao
authors.initials: H
authors.lastname: Liang
authors.forename: Jing
authors.initials: J
authors.lastname: Han
authors.forename: Rui-Jie
authors.initials: RJ
authors.lastname: Zhao
authors.forename: Yan
authors.initials: Y
authors.lastname: Cheng
mesh_terms: D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000187:drug effects / Q000378:metabolism; D001093:Arachidonate 15-Lipoxygenase / Q000187:drug effects / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects*; D015153:Blotting, Western; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D011809:Quinones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism
chemical_list: C475064:12-15-lipoxygenase; D018696:Neuroprotective Agents; D011809:Quinones; C085278:hydroxysafflor yellow A; D002599:Chalcone; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase