The effect of Scutellaria baicalensis stem-leaf flavonoids on spatial learning and memory in chronic cerebral ischemia-induced vascular dementia of rats.
Flavonoids have been shown to improve cognitive function and delay the dementia progression. However, the underlying mechanisms remain elusive. In the present study, we examined the effect of Scutellaria baicalensis stem-leaf total flavonoids (SSTFs) extracted from S. baicalensis Georgi on spatial learning and memory in a vascular dementia (VaD) rat model and explored its molecular mechanisms. The VaD rats were developed by permanent bilateral occlusion of the common carotid artery. Seven days after recovery, the VaD rats were treated with either 50 or 100 mg/kg of SSTF for 60 days. The spatial learning and memory was evaluated in the Morris water maze (MWM) test. The tau hyperphosphorylation and the levels of the related protein kinases or phosphatases were examined by western blot analysis. In VaD rats, SSTF treatment at 100 mg/kg significantly reduced the escape latency in training trial in MWM test. In the probe trial, SSTF treatment increased the searching time and travel distance in the target quadrant. SSTF treatment inhibited the tau phosphorylation in both cortex and hippocampus in VaD rats. Meanwhile, SSTF reduced the activity of glycogen synthase kinase 3β and cyclin-dependent kinase 5 in VaD rats. In contrast, SSTF treatment increased the level of the protein phosphatase 2A subunit B in VaD rats. SSTF treatment significantly improved the spatial cognition in VaD rats. Our results suggest that SSTF may alleviate tau-hyperphosphorylation-induced neurotoxicity through coordinating the activity of kinases and phosphatase after a stroke. SSTF may be developed into promising novel therapeutics for VaD.
Department of Neurology, Shandong Provincial Hospital, Shandong University, Jinan 250013, China Department of Neurology, Third Hospital of Hangzhou, Hangzhou 310009, China.
Yanjing
Y
Cao
Department of Neurology, Third Hospital of Hangzhou, Hangzhou 310009, China.
Lizhen
L
Liang
Department of Histology and Embryology, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Jian
J
Xu
Department of Neurology, Third Hospital of Hangzhou, Hangzhou 310009, China.
Jiali
J
Wu
Department of Neurology, Third Hospital of Hangzhou, Hangzhou 310009, China.
Yongxing
Y
Yan
Department of Neurology, Third Hospital of Hangzhou, Hangzhou 310009, China.
Ping
P
Lin
Department of Neurology, Third Hospital of Hangzhou, Hangzhou 310009, China.
Qiang
Q
Chen
Department of Neurology, Third Hospital of Hangzhou, Hangzhou 310009, China.
Fengming
F
Zheng
Department of Neurology, Third Hospital of Hangzhou, Hangzhou 310009, China.
Qin
Q
Wang
Department of Neurology, Third Hospital of Hangzhou, Hangzhou 310009, China.
Qian
Q
Ren
Department of Neurology, The Second People's Hospital of Weifang, Weifang 261041, China.
Zengmei
Z
Gou
Department of Neurology, Shandong Provincial Hospital, Shandong University, Jinan 250013, China duyifeng2014@163.com.
Yifeng
Y
Du
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002545:Brain Ischemia / Q000150:complications; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism; D015140:Dementia, Vascular / Q000188:drug therapy* / Q000209:etiology / Q000523:psychology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology*; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D054648:Protein Phosphatase 2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D031364:Scutellaria baicalensis; D065853:Spatial Learning / Q000187:drug effects*; D016875:tau Proteins / Q000378:metabolism
D004365:Drugs, Chinese Herbal; D005419:Flavonoids; C489131:Mapt protein, rat; D016875:tau Proteins; D051360:Cyclin-Dependent Kinase 5; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; C495907:Cdk5 protein, rat; D054648:Protein Phosphatase 2
deficits of spatial learning and memory; flavonoid; hyperphosphorylated tau; vascular dementia