title: Effects of fisetin on hyperhomocysteinemia-induced experimental endothelial dysfunction and vascular dementia.
abstract: This study was designed to investigate the effects of fisetin (FST) on hyperhomocysteinemia (HHcy)-induced experimental endothelial dysfunction (ED) and vascular dementia (VaD) in rats. Wistar rats were randomly divided into 8 groups: control, vehicle control, l-methionine, FST (5, 10, and 25 mg/kg, p.o.), FST-per se (25 mg/kg, p.o.), and donepezil (0.1 mg/kg, p.o.). l-Methionine administration (1.7 g/kg, p.o.) for 32 days induced HHcy. ED and VaD induced by HHcy were determined by vascular reactivity measurements, behavioral analysis using Morris water maze and Y-maze, along with a biochemical and histological evaluation of thoracic aorta and brain tissues. Administration of l-methionine developed behavioral deficits; triggered brain lipid peroxidation (LPO); compromised brain acetylcholinesterase activity (AChE); and reduced the levels of brain superoxide dismutase (SOD), brain catalase (CAT), brain reduced glutathione (GSH), and serum nitrite; and increased serum homocysteine and cholesterol levels. These effects were accompanied by decreased vascular NO bioavailability, marked intimal thickening of the aorta, and multiple necrotic foci in brain cortex. HHcy-induced alterations in the activities of SOD, CAT, GSH, AChE, LPO, behavioral deficits, ED, and histological aberrations were significantly attenuated by treatment with fisetin in a dose-dependent manner. Collectively, our results indicate that fisetin exerts endothelial and neuroprotective effects against HHcy-induced ED and VaD.
authors.affiliation: a Department of Pharmacology, Anurag Group of Institutions (Formerly Lalitha College of Pharmacy), Hyderabad, Telangana, India.|b Center for Pharmaceutical Sciences and Research and Development Cell, Jawaharlal Nehru Technological University, Hyderabad, Telangana, India.
authors.forename: Boyina
authors.initials: B
authors.lastname: Hemanth Kumar
authors.affiliation: a Department of Pharmacology, Anurag Group of Institutions (Formerly Lalitha College of Pharmacy), Hyderabad, Telangana, India.|c Graduate School of Biomedical Sciences, Rowan University, Stratford, NJ 08084, USA.
authors.forename: Ravula
authors.initials: R
authors.lastname: Arun Reddy
authors.affiliation: d Animal House Facility, CSIR-Centre for Cellular and Molecular Biology (CCMB), Hyderabad, Telangana 500007, India.
authors.forename: Jerald
authors.initials: J
authors.lastname: Mahesh Kumar
authors.affiliation: e National Institute of Nutrition (ICMR), Food & Drug Toxicology Research Centre (FDTRC), Hyderabad, Telangana 500007, India.
authors.forename: B
authors.initials: B
authors.lastname: Dinesh Kumar
authors.affiliation: a Department of Pharmacology, Anurag Group of Institutions (Formerly Lalitha College of Pharmacy), Hyderabad, Telangana, India.|f Maratha Mandal Central Research Laboratory, Belagavi-590010, Karnataka, India.
authors.forename: Prakash V
authors.initials: PV
authors.lastname: Diwan
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000473:pathology; D001921:Brain / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D015140:Dementia, Vascular / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D005419:Flavonoids / Q000494:pharmacology* / Q000627:therapeutic use*; D044948:Flavonols; D005978:Glutathione / Q000378:metabolism; D006710:Homocysteine / Q000097:blood; D020138:Hyperhomocysteinemia / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D007189:Indans / Q000627:therapeutic use; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018782:Maze Learning; D008715:Methionine / Q000009:adverse effects; D009336:Necrosis / Q000188:drug therapy / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D010880:Piperidines / Q000627:therapeutic use; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D005419:Flavonoids; D044948:Flavonols; D007189:Indans; D009573:Nitrites; D010880:Piperidines; D006710:Homocysteine; D009569:Nitric Oxide; D000077265:Donepezil; D002784:Cholesterol; D008715:Methionine; D002374:Catalase; D013482:Superoxide Dismutase; D000110:Acetylcholinesterase; D005978:Glutathione; C017875:fisetin
keywords: Morris water maze; acetylcholinesterase; acétylcholinestérase; foyers nécrotiques; l-NAME; l-methionine; l-méthionine; labyrinthe aquatique de Morris; necrotic foci