Neuroprotection by Acetyl-11-Keto-β-Boswellic Acid, in Ischemic Brain Injury Involves the Nrf2/HO-1 defense Pathway

被引:153
作者
Ding, Yi [1 ]
Chen, MinChun [1 ]
Wang, Min [3 ]
Wang, MingMing [1 ]
Zhang, Tiejun [2 ]
Park, Jongsun [2 ]
Zhu, YanRong [1 ]
Guo, Chao [1 ]
Jia, YanYan [1 ]
Li, Yuwen [1 ]
Wen, AiDong [1 ]
机构
[1] Fourth Mil Med Univ, Xijing Hosp, Dept Pharm, Xian, Peoples R China
[2] Chungnam Natl Univ, Dept Pharmacol, Taejon, South Korea
[3] Fourth Mil Med Univ, Sch Pharm, Dept Pharmacol, Xian, Peoples R China
基金
中国国家自然科学基金;
关键词
HEME OXYGENASE-1; MOLECULAR-MECHANISMS; BOSWELLIA-SERRATA; OXIDATIVE STRESS; PROTECTS; ACTIVATION; INDUCTION; COLITIS; EXTRACT; DAMAGE;
D O I
10.1038/srep07002
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Stroke is a complex disease involved oxidative stress-related pathways in its pathogenesis. The nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway has been considered a potential target for neuroprotection in stroke. Acetyl-11-Keto-beta-Boswellic Acid (AKBA) is an active triterpenoid compound from the extract of Boswellia serrate. The present study was to determine whether AKBA, a novel Nrf2 activator, can protect against cerebral ischemic injury. The stroke model was produced in Sprague-Dawley rats via middle cerebral artery occlusion. To model ischemia-like conditions in vitro, primary cultured cortical neurons were exposed to transient oxygen and glucose deprivation (OGD). Treatment of AKBA significantly reduced infarct volumes and apoptotic cells, and also increased neurologic scores by elevating the Nrf2 and HO-1 expression in brain tissues in middle cerebral artery occlusion (MCAO) rats at 48 hours post reperfusion. In primary cultured neurons, AKBA increased the Nrf2 and HO-1 expression, which provided protection against OGD-induced oxidative insult. Additionally, AKBA treatment increased Nrf2 binding activity to antioxidant-response elements (ARE). The protective effect of AKBA was attenuated by knockdown of Nrf2 or HO-1. In conclusion, these findings provide evidence that AKBA protects neurons against ischemic injury, and this neuroprotective effect involves the Nrf2/HO-1 pathway.
引用
收藏
页数:9
相关论文
共 35 条
[1]   Sulforaphane preconditioning of the Nrf2/HO-1 defense pathway protects the cerebral vasculature against blood-brain barrier disruption and neurological deficits in stroke [J].
Alfieri, Alessio ;
Srivastava, Sail ;
Siow, Richard C. M. ;
Cash, Diana ;
Modo, Michel ;
Duchen, Michael R. ;
Fraser, Paul A. ;
Williams, Steven C. R. ;
Mann, Giovanni E. .
FREE RADICAL BIOLOGY AND MEDICINE, 2013, 65 :1012-1022
[2]   Boswellic acids extract attenuates pulmonary fibrosis induced by bleomycin and oxidative stress from gamma irradiation in rats [J].
Ali, Eman Noaman ;
Mansour, Somaya Zakaria .
CHINESE MEDICINE, 2011, 6
[3]   Apoptotic Mechanisms After Cerebral Ischemia [J].
Broughton, Brad R. S. ;
Reutens, David C. ;
Sobey, Christopher G. .
STROKE, 2009, 40 (05) :E331-E339
[4]  
CHAN PH, 1994, BRAIN PATHOL, V4, P59
[5]   A COMPARATIVE-EVALUATION OF THIOBARBITURIC ACID METHODS FOR THE DETERMINATION OF MALONDIALDEHYDE IN BIOLOGICAL-MATERIALS [J].
DRAPER, HH ;
SQUIRES, EJ ;
MAHMOODI, H ;
WU, J ;
AGARWAL, S ;
HADLEY, M .
FREE RADICAL BIOLOGY AND MEDICINE, 1993, 15 (04) :353-363
[6]   Targeting Heme Oxygenase-1 in Vascular Disease [J].
Durante, William .
CURRENT DRUG TARGETS, 2010, 11 (12) :1504-1516
[7]   The selective 5-LOX inhibitor 11-keto-β-boswellic acid protects against myocardial ischemia reperfusion injury in rats: involvement of redox and inflammatory cascades [J].
Elshazly, Shimaa M. ;
Abd El Motteleb, Dalia M. ;
Nassar, Noha N. .
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 2013, 386 (09) :823-833
[8]   Heart Disease and Stroke Statistics-2013 Update A Report From the American Heart Association [J].
Go, Alan S. ;
Mozaffarian, Dariush ;
Roger, Veronique L. ;
Benjamin, Emelia J. ;
Berry, Jarett D. ;
Borden, William B. ;
Bravata, Dawn M. ;
Dai, Shifan ;
Ford, Earl S. ;
Fox, Caroline S. ;
Franco, Sheila ;
Fullerton, Heather J. ;
Gillespie, Cathleen ;
Hailpern, Susan M. ;
Heit, John A. ;
Howard, Virginia J. ;
Huffman, Mark D. ;
Kissela, Brett M. ;
Kittner, Steven J. ;
Lackland, Daniel T. ;
Lichtman, Judith H. ;
Lisabeth, Lynda D. ;
Magid, David ;
Marcus, Gregory M. ;
Marelli, Ariane ;
Matchar, David B. ;
McGuire, Darren K. ;
Mohler, Emile R. ;
Moy, Claudia S. ;
Mussolino, Michael E. ;
Nichol, Graham ;
Paynter, Nina P. ;
Schreiner, Pamela J. ;
Sorlie, Paul D. ;
Stein, Joel ;
Turan, Tanya N. ;
Virani, Salim S. ;
Wong, Nathan D. ;
Woo, Daniel ;
Turner, Melanie B. .
CIRCULATION, 2013, 127 (01) :E6-E245
[9]   Effect of Boswellia serrata on Antioxidant Status in an Experimental Model of Colitis Rats Induced by Acetic Acid [J].
Hartmann, Renata Minuzzo ;
Morgan Martins, Maria Isabel ;
Tieppo, Juliana ;
Fillmann, Henrique Sarubbi ;
Marroni, Norma Possa .
DIGESTIVE DISEASES AND SCIENCES, 2012, 57 (08) :2038-2044
[10]   Targeting Nrf2-Mediated Gene Transcription by Extremely Potent Synthetic Triterpenoids Attenuate Dopaminergic Neurotoxicity in the MPTP Mouse Model of Parkinson's Disease [J].
Kaidery, Navneet Ammal ;
Banerjee, Rebecca ;
Yang, Lichuan ;
Smirnova, Natalya A. ;
Hushpulian, Dmitry M. ;
Liby, Karen T. ;
Williams, Charlotte R. ;
Yamamoto, Masayuki ;
Kensler, Thomas W. ;
Ratan, Rajiv R. ;
Sporn, Michael B. ;
Beal, M. Flint ;
Gazaryan, Irina G. ;
Thomas, Bobby .
ANTIOXIDANTS & REDOX SIGNALING, 2013, 18 (02) :139-157