title: Icariin, a major constituent of flavonoids from Epimedium brevicornum, protects against cognitive deficits induced by chronic brain hypoperfusion via its anti-amyloidogenic effect in rats.
abstract: Chronic cerebral hypoperfusion is considered to be a pivotal contributing factor of cognitive impairments that occur in vascular dementia and Alzheimer's disease, and ideal drug treatment for these diseases is unavailable. Hence, this study was designed to investigate the protective effects of icariin, a major constituent of flavonoids from the Chinese medicinal herb Epimedium brevicornum, on cognitive impairments and neuronal morphological damage induced by permanent occlusion of bilateral common carotid arteries (BCCAO) in rats, and further explore the potential mechanisms. This study found that BCCAO could induce cognitive deficits and neuronal morphological damage, along with deposition of beta-amyloid (Aβ) in rat hippocampus. However, oral administration of icariin twice per day for 23days might attenuate cognitive deficits and neuronal morphological damage induced by BCCAO. Subsequently, icariin decreased the level of Aβ in rat hippocampus subjected to BCCAO. Administration of icariin reduced the expressions of amyloid precursor protein (APP), beta-secretase 1 (BACE1), and increased the expressions of insulin-degrading enzyme (IDE) and a disintegrin and metalloproteinase domain 10 (ADAM10) in rat hippocampus. Furthermore, icariin afforded beneficial actions in suppressing transforming growth factor-β1 (TGF-β1) signaling via inhibition of Smad2/3 phosphorylation. In summary, icariin is effective in improving cognitive deficits and hippocampus morphological alterations subjected to BCCAO. This protection appears to be due to the decreased expressions of both APP and BACE1, and the increased expressions of both IDE and ADAM10, resulting in a decrease in the level of insoluble Aβ fragments in rat hippocampus. Inhibitions of TGF-β1 signaling and Smad2/3 phosphorylation are involved in the course.
authors.affiliation: Department of Pharmacology and the Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Guizhou, China.
authors.forename: Wen-Xian
authors.initials: WX
authors.lastname: Li
authors.affiliation: Department of Pharmacology and the Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Guizhou, China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Deng
authors.affiliation: Department of Pharmacology and the Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Guizhou, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Pharmacology and the Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Guizhou, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Pharmacology and the Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Guizhou, China.
authors.forename: Hui-Yu
authors.initials: HY
authors.lastname: Liu
authors.affiliation: Department of Pharmacology and the Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Guizhou, China.
authors.forename: Jing-Shan
authors.initials: JS
authors.lastname: Shi
authors.affiliation: Department of Pharmacology and the Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Guizhou, China. Electronic address: gqh@zmc.edu.cn.
authors.forename: Qi-Hai
authors.initials: QH
authors.lastname: Gong
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors; D017536:Carotid Artery, Common / Q000473:pathology; D016893:Carotid Stenosis / Q000473:pathology; D002561:Cerebrovascular Disorders / Q000150:complications*; D003072:Cognition Disorders / Q000209:etiology / Q000517:prevention & control*; D034181:Epimedium / Q000737:chemistry*; D005419:Flavonoids / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D005419:Flavonoids; D053773:Transforming Growth Factor beta1; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509281:Bace1 protein, rat; C056599:icariin
keywords: Beta-amyloid; Chronic cerebral hypoperfusion; Icariin; Permanent occlusion of bilateral common carotid arteries; Transforming growth factor-β(1) signaling