Protective effect of quercetin against intracerebral streptozotocin induced reduction in cerebral blood flow and impairment of memory in mice.
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 cholinergic dysfunction in brain following intracerebral (i.c.) streptozotocin (STZ) administration in mice. STZ (0.5mg/kg, i.c.) was administered twice at an interval of 48h. We found a significant reduction in CBF as measured by Laser Doppler Flowmetry (LDF). The brain energy metabolism was also altered as evidenced by significant reduction in brain ATP content. Daily treatment with quercetin (2.5, 5 and 10mg/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 levels. 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.
Tota
Santoshkumar
S
Division of Pharmacology, Central Drug Research Institute, CSIR, Chattar Manzil, Lucknow, U.P., India.
Awasthi
Himani
H
Kamat
Pradeep Kumar
PK
Nath
Chandishwar
C
Hanif
Kashif
K
D000110:Acetylcholinesterase / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects; D001786:Blood Glucose / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D007276:Injections, Intraventricular; D017078:Laser-Doppler Flowmetry / Q000379:methods; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009573:Nitrites / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*; D018709:Statistics, Nonparametric; D013311:Streptozocin / Q000009:adverse effects / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D001786:Blood Glucose; D009573:Nitrites; D008315:Malondialdehyde; D013311:Streptozocin; D000255:Adenosine Triphosphate; D011794:Quercetin; D000110:Acetylcholinesterase; D005978:Glutathione