Baicalein is neuroprotective in rat MCAO model: Role of 12/15-lipoxygenase, mitogen-activated protein kinase and cytosolic phospholipase A2

被引:84
作者
Cui, Lili [1 ]
Zhang, Xiangjian [1 ]
Yang, Rui [1 ]
Liu, Lingling [1 ]
Wang, Lina [1 ]
Li, Min [1 ]
Du, Wei [1 ]
机构
[1] Hebei Med Univ, Hosp 2, Dept Neurol, Shijiazhuang 050000, Hebei, Peoples R China
关键词
Baicalein; Cerebral ischemia; Neuroprotection; Lipoxygenase; Mitogen-activated protein kinase; Phospholipase A2; CEREBRAL-ARTERY OCCLUSION; LIPID-PEROXIDATION; ARACHIDONIC-ACID; BRAIN; ISCHEMIA; A(2); MECHANISMS; STROKE; EDEMA; CELLS;
D O I
10.1016/j.pbb.2010.07.007
中图分类号
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要
Inflammatory damage and oxidative stress play an important role in cerebral ischemic pathogenesis and may represent a target for treatment. Baicalein, isolated from the traditional Chinese herbal medicine Huangqin, is an antioxidant and anti-inflammatory agent on one hand and a lipoxygenase inhibitor on the other hand. However, little is known regarding the mechanism of baicalein's neuroprotection in ischemic stroke. We therefore investigated the potential neuroprotective effects of baicalein and explored the underlying mechanisms. Male, Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAO) and baicalein was administered intravenously immediately after cerebral ischemia. At 24 h after MCAO neurological deficit, brain water content and infarct sizes were measured. Immunohistochemistry, western blot and reverse transcription-polymerase chain reaction (RT-PCR) were used to analyse the expression of 12/15-lipoxygenase (12/15-LOX), p38 mitogen-activated protein kinase (p38 MAPK) and cytosolic phospholipase A2 (cPIA2) at gene and protein levels in ischemic brain cortex. The results showed that baicalein improved neurological deficit, reduced brain water content and infarct sizes, and downregulated the overexpression of 12/15-LOX, p38 MAPK and cPLA2 typically seen with MCAO. The results indicated that baicalein protected the brain from damage caused by MCAO, and this effect may be through downregulation of 12/15-LOX, p38 MAPK and cPLA2 expression. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:469 / 475
页数:7
相关论文
共 51 条
[1]   Citicoline decreases phospholipase A2 stimulation and hydroxyl radical generation in transient cerebral ischemia [J].
Adibhatla, RM ;
Hatcher, JF .
JOURNAL OF NEUROSCIENCE RESEARCH, 2003, 73 (03) :308-315
[2]   EVALUATION OF 2, 3, 5-TRIPHENYLTETRAZOLIUM CHLORIDE AS A STAIN FOR DETECTION AND QUANTIFICATION OF EXPERIMENTAL CEREBRAL INFARCTION IN RATS [J].
BEDERSON, JB ;
PITTS, LH ;
GERMANO, SM ;
NISHIMURA, MC ;
DAVIS, RL ;
BARTKOWSKI, HM .
STROKE, 1986, 17 (06) :1304-1308
[3]   Brain genomic response following hypoxia and re-oxygenation in the neonatal rat - Identification of genes that might contribute to hypoxia-induced ischemic tolerance [J].
Bernaudin, M ;
Tang, Y ;
Reilly, M ;
Petit, E ;
Sharp, FR .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (42) :39728-39738
[4]   BRAIN EDEMA - INDUCTION IN CORTICAL SLICES BY POLY-UNSATURATED FATTY-ACIDS [J].
CHAN, PH ;
FISHMAN, RA .
SCIENCE, 1978, 201 (4353) :358-360
[5]   Reactive oxygen radicals in signaling and damage in the ischemic brain [J].
Chan, PH .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2001, 21 (01) :2-14
[6]   Post-injury baicalein improves histological and functional outcomes and reduces inflammatory cytokines after experimental traumatic brain injury [J].
Chen, S-F ;
Hsu, C-W ;
Huang, W-H ;
Wang, J-Y .
BRITISH JOURNAL OF PHARMACOLOGY, 2008, 155 (08) :1279-1296
[7]   Baicalein inhibition of oxidative-stress-induced apoptosis via modulation of ERKs activation and induction of HO-1 gene expression in rat glioma cells C6 [J].
Chen, Yen-Chou ;
Chow, Jyh-Ming ;
Lin, Cheng-Wei ;
Wu, Chin-Yen ;
Shen, Shing-Chuan .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 2006, 216 (02) :263-273
[8]   Activation of P38 mitogen-activated protein kinase/cytosolic phospholipase A2 cascade in hydroperoxide-stressed platelets [J].
Coulon, L ;
Calzada, C ;
Moulin, P ;
Véricel, E ;
Lagarde, M .
FREE RADICAL BIOLOGY AND MEDICINE, 2003, 35 (06) :616-625
[9]   The inflammatory response in cerebral ischemia: Focus on cytokines in stroke patients [J].
De Simoni, MG ;
Milia, P ;
Barba, M ;
De Luigi, A ;
Parnetti, L ;
Gallai, V .
CLINICAL AND EXPERIMENTAL HYPERTENSION, 2002, 24 (7-8) :535-542
[10]   GLOBAL CEREBRAL-ISCHEMIA IN THE RAT - ONLINE MONITORING OF OXYGEN-FREE RADICAL PRODUCTION USING CHEMILUMINESCENCE IN-VIVO [J].
DIRNAGL, U ;
LINDAUER, U ;
THEM, A ;
SCHREIBER, S ;
PFISTER, HW ;
KOEDEL, U ;
RESZKA, R ;
FREYER, D ;
VILLRINGER, A .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 1995, 15 (06) :929-940