Behavioural Brain Research 209 (2010) 73–79 Contents lists available at ScienceDirect Behavioural Brain Research journal homepage: www.elsevier.com/locate/bbr Research report Protective effect of quercetin against intracerebral streptozotocin induced reduction in cerebral blood flow and impairment of memory in mice Santoshkumar Tota a , Himani Awasthi a , Pradeep Kumar Kamat a , Chandishwar Nath b , Kashif Hanif a,∗ a Division of Pharmacology, Central Drug Research Institute, CSIR, Chattar Manzil, Lucknow, U.P., India b Division of Toxicology, Central Drug Research Institute, CSIR, Lucknow, U.P., India article info Article history: Received 21 August 2009 Received in revised form 14 January 2010 Accepted 15 January 2010 Available online 22 January 2010 Keywords: Cerebral blood flow ATP Memory impairment Oxidative stress Quercetin Streptozotocin abstract The aim of the present study is to investigate the effect of quercetin, a naturally occurring flavonoid, on cerebral blood flow (CBF), brain energy metabolism, memory impairment, oxidative stress and cholin- ergic dysfunction in brain following intracerebral (i.c.) streptozotocin (STZ) administration in mice. STZ (0.5 mg/kg, i.c.) was administered twice at an interval of 48 h. We found a significant reduction in CBF as measured by Laser Doppler Flowmetry (LDF). The brain energy metabolism was also altered as evi- denced by significant reduction in brain ATP content. Daily treatment with quercetin (2.5, 5 and 10 mg/kg, p.o.) starting from the first dose of STZ showed a dose-dependent restoration of CBF and ATP content. Further, quercetin prevented STZ induced memory impairment as assessed by Morris water maze and passive avoidance tests. Biochemical analysis revealed that STZ significantly increased malondialdehyde (MDA), nitrite and depleted glutathione (GSH) levels in the mice brain. Quercetin decreased oxidative and nitrosative stress as evidenced by a significant decrease in MDA, nitrite and increase in GSH lev- els. Quercetin also attenuated elevated acetylcholinesterase activity in the STZ-treated mice. Neither STZ (i.c.) nor quercetin showed any change in locomotor activity and blood glucose level. The present study demonstrates the beneficial effects of quercetin in improving CBF along with preventing memory impairment, oxidative stress, altered brain energy metabolism and cholinergic dysfunction caused by STZ in mice. Therefore, consumption of dietary stuff rich in quercetin should be encouraged to ward off dementia associated with vascular and neurodegenerative disorders. © 2010 Elsevier B.V. All rights reserved. 1. Introduction The flavonoids are a group of naturally occurring compounds found in plants and are frequently consumed in human diet. Flavonoids show antibacterial, anti-inflammatory [30], antiallergic [44], antiviral, antitumor [55], antiischemic [34], vasodilatory activ- ity [49] and a strong antioxidizing action [4,61]. In flavonoid family, widely distributed quercetin (3, 5, 7, 3 ′ ,4 ′ -pentahydroxyflavone) exhibit strong anti-inflammatory, anticancer, antiallergic and vasorelaxation activities because of its potent antioxidant action [43,62]. Recently, quercetin exhibited protective effect against memory impairment induced by d-galactose and repeated cerebral ischemia in animals [38,59]. Alzheimer’s disease [AD] is the most common cause of demen- tia in the elderly [19]. All forms of dementia of Alzheimer’s type are characterized by abnormalities in glucose metabolism, reduced glucose utilization and levels of energy rich phosphates like ATP, ADP, etc. [2,48]. Disturbed energy metabolism is intricately asso- ∗ Corresponding author. Tel.: +91 522 2612411 18x4444; fax: +91 522 2623405. E-mail address: k hanif@cdri.res.in (K. Hanif). ciated with increased oxidative stress that results in oxidation of biomolecules and initiates excitotoxic neuronal cell damage [39,52]. On the other hand, reduction in brain glucose below a crit- ical level also affects cholinergic system. This decreases the rate of acetylcholine synthesis by lowering concentrations of acetyl- coenzyme A, a derivative of glucose [21]. AD and other types of dementia, besides above stated char- acteristics are also associated with reduced cerebral blood flow (CBF) [50,58] due to vascular amyloidosis, oxidative stress and endothelial dysfunction. Cerebral microcirculatory impairment, may initiate pathophysiological changes in the progression of AD [1,14]. Relationship between CBF and brain function is further buttressed by the fact that an increase in CBF is beneficial for cogni- tive function [46]. Natural products also modulate CBF. Flavonoid rich cocoa increased local CBF to grey matter by up to 60% 2–3 h postconsumption [20]. Recently we have shown that the natural antioxidant curcumin improves CBF in STZ induced memory deficit model [3] Various pathological aspects of AD like impaired brain glu- cose and energy metabolism are closely mimicked in rats after subdiabetogenic intracerebroventricular (i.c.v.) injection of strep- tozotocin (STZ) [15,33,41] which leads to progressive deficits in 0166-4328/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.bbr.2010.01.017