title: Effects of crocin on reperfusion-induced oxidative/nitrative injury to cerebral microvessels after global cerebral ischemia.
abstract: This paper studied the effects of crocin, a pharmacologically active component of Crocus sativus L., on ischemia/reperfusion (I/R) injury in mice cerebral microvessels. Transient global cerebral ischemia (20 min), followed by 24 h of reperfusion, significantly promoted the generation of nitric oxide (NO) and malondialdehyde (MDA) in cortical microvascular homogenates, as well as markedly reduced the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) and promoted the activity of nitric oxide synthase (NOs). Reperfusion for 24 h led to serous edema with substantial microvilli loss, vacuolation, membrane damage and mitochondrial injuries in cortical microvascular endothelial cells (CMEC). Furthermore, enhanced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and decreased expression of matrix metalloproteinase-9 (MMP-9) were detected in cortical microvessels after I (20 min)/R (24 h). Reperfusion for 24 h also induced membrane (functional) G protein-coupled receptor kinase 2 (GRK2) expression, while it reduced cytosol GRK2 expression. Pretreatment with crocin markedly inhibited oxidizing reactions and modulated the ultrastructure of CMEC in mice with 20 min of bilateral common carotid artery occlusion (BCCAO) followed by 24 h of reperfusion in vivo. Furthermore, crocin inhibited GRK2 translocation from the cytosol to the membrane and reduced ERK1/2 phosphorylation and MMP-9 expression in cortical microvessels. We propose that crocin protects the brain against excessive oxidative stress and constitutes a potential therapeutic candidate in transient global cerebral ischemia.
authors.affiliation: Research Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, 1, Xi Yuan yard Road, Haidian District, Beijing 100091, PR China. yongqiuzheng@sina.com
authors.forename: Yong-Qiu
authors.initials: YQ
authors.lastname: Zheng
authors.forename: Jian-Xun
authors.initials: JX
authors.lastname: Liu
authors.forename: Jan-Nong
authors.initials: JN
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Xu
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000378:metabolism / Q000473:pathology; D001929:Brain Edema / Q000209:etiology / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology*; D002338:Carotenoids / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000098:blood supply*; D042783:Endothelial Cells / Q000187:drug effects / Q000648:ultrastructure; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D054769:G-Protein-Coupled Receptor Kinase 2; D005979:Glutathione Peroxidase / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D015427:Reperfusion Injury / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D013347:Subcellular Fractions / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014018:Tissue Distribution; D051552:beta-Adrenergic Receptor Kinases / Q000378:metabolism
chemical_list: D009569:Nitric Oxide; D002338:Carotenoids; D008315:Malondialdehyde; C029036:crocin; D005979:Glutathione Peroxidase; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; C496568:GRK2 protein, mouse; D051552:beta-Adrenergic Receptor Kinases; D054769:G-Protein-Coupled Receptor Kinase 2; D048049:Extracellular Signal-Regulated MAP Kinases; D020780:Matrix Metalloproteinase 9