Neuroprotection by acetyl-11-keto-β-Boswellic acid, in ischemic brain injury involves the Nrf2/HO-1 defense pathway.
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-β-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.
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University.
Yi
Y
Ding
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University.
MinChun
M
Chen
Department of Pharmacology, School of Pharmacy, Fourth Military Medical University.
Min
M
Wang
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University.
MingMing
M
Wang
Department of Pharmacology, Chungnam National University.
Tiejun
T
Zhang
Department of Pharmacology, Chungnam National University.
Jongsun
J
Park
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University.
YanRong
Y
Zhu
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University.
Chao
C
Guo
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University.
YanYan
Y
Jia
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University.
YuWen
Y
Li
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University.
AiDong
A
Wen
D000818:Animals; D061745:Antioxidant Response Elements; D017209:Apoptosis / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015687:Cell Hypoxia / Q000235:genetics; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D005947:Glucose / Q000172:deficiency; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D020521:Stroke / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014315:Triterpenes / Q000494:pharmacology*
D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; C495637:Nfe2l2 protein, rat; D034741:RNA, Small Interfering; D014315:Triterpenes; C094432:acetyl-11-ketoboswellic acid; D051547:Heme Oxygenase-1; D005947:Glucose; D010100:Oxygen