title: Protective role of luteolin against cognitive dysfunction induced by chronic cerebral hypoperfusion in rats.
abstract: Chronic cerebral hypoperfusion, a mild ischemic condition, is associated with the cognitive deficits of Alzheimer's disease (AD). Luteolin, a polyphenolic compound found in foods of plant origin, belonging to the flavone subclass of flavonoids, has been shown to possess antioxidant, anti-inflammatory and antitumorigenic properties. In the present study, the effects of luteolin on chronic cerebral hypoperfusion-associated neurocognitive pathologies were investigated by using rats with permanent bilateral common carotid artery occlusion, a rat model of chronic cerebral hypoperfusion. As expected, we found that luteolin could attenuate cognitive dysfunction in chronic cerebral hypoperfused rats, as assessed using Morris water maze tests. Daily oral administration of luteolin (50, 100 and 200mg/kg) significantly scavenged oxygen free radicals, enhanced antioxidant potential, decreased the lipid peroxide production and suppressed inflammatory reaction in the cerebral cortex and hippocampus induced by chronic cerebral hypoperfusion. Meanwhile, the results indicated that cerebral hypoperfusion activated nuclear factor-κB (NF-κB), increased the expression of β-site amyloid precursor protein cleaving enzyme (BACE1), as well as elevated amyloid beta (Aβ) levels in the cortex and hippocampus. However, long-term administration of luteolin significantly down-regulated the expression of NF-κB and BACE1, accompanied by diminishing the deposition of Aβ. Our results suggest a potential therapeutic use of luteolin for cerebral hypoperfusion associated cognitive dysfunction in AD.
authors.affiliation: School of Pharmacy, Xuzhou Medical College, Xuzhou, 221004 Jiangsu Province, PR China. Electronic address: cbpe201104@163.com.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Fu
authors.affiliation: School of Pharmacy, Xuzhou Medical College, Xuzhou, 221004 Jiangsu Province, PR China. Electronic address: cbpe201206@163.com.
authors.forename: Jingzheng
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of dermatological of People's hospital of Liaocheng, Liaocheng, 252000, Shandong Province, PR China. Electronic address: lc_gl8688@163.com.
authors.forename: Ling
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of nephrology of the Second People's hospital of Liaocheng affiliated to Taishan Meidical College, Linqing, 252600, Shandong Province, PR China. Electronic address: xuyaguang1986@163.com.
authors.forename: Yaguang
authors.initials: Y
authors.lastname: Xu
authors.affiliation: School of Pharmacy, Xuzhou Medical College, Xuzhou, 221004 Jiangsu Province, PR China. Electronic address: rzyx7@sina.com.
authors.forename: Lingyan
authors.initials: L
authors.lastname: Sun
authors.affiliation: School of Pharmacy, Xuzhou Medical College, Xuzhou, 221004 Jiangsu Province, PR China. Electronic address: cbpe201202@163.com.
authors.forename: Shuaishuai
authors.initials: S
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Xuzhou Medical College, Xuzhou, 221004 Jiangsu Province, PR China. Electronic address: cbpe201204@163.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Feng
authors.affiliation: School of Pharmacy, Xuzhou Medical College, Xuzhou, 221004 Jiangsu Province, PR China. Electronic address: jifeng0241527@163.com.
authors.forename: Lingshan
authors.initials: L
authors.lastname: Gou
authors.affiliation: School of Pharmacy, Xuzhou Medical College, Xuzhou, 221004 Jiangsu Province, PR China. Electronic address: zhamgling1999@163.com.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Xuzhou Medical College, Xuzhou, 221004 Jiangsu Province, PR China. Electronic address: cbpe201087@gmail.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism*; D003072:Cognition Disorders / Q000150:complications / Q000188:drug therapy* / Q000209:etiology; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D047311:Luteolin / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000378:metabolism; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016166:Free Radical Scavengers; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D016328:NF-kappa B; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C052994:interleukin-1beta (163-171); D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509281:Bace1 protein, rat; D047311:Luteolin
keywords: Amyloid beta; Anti-inflammatory; Antioxidant; Chronic cerebral hypoperfusion; Luteolin