title: Posttreatment with 11-Keto-β-Boswellic Acid Ameliorates Cerebral Ischemia-Reperfusion Injury: Nrf2/HO-1 Pathway as a Potential Mechanism.
abstract: Oxidative stress is well known to play a pivotal role in cerebral ischemia-reperfusion injury. 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. 11-Keto-β-boswellic acid (KBA) is a triterpenoid compound from extracts of Boswellia serrata. The aim of the present study was to determine whether KBA, a novel Nrf2 activator, can protect against cerebral ischemic injury. Middle cerebral artery occlusion (MCAO) was operated on male Sprague-Dawley rats. KBA (25 mg/kg) applied 1 h after reperfusion significantly reduced infarct volumes and apoptotic cells as well as increased neurologic scores at 48 h after reperfusion. Meanwhile, posttreatment with KBA significantly decreased malondialdehyde (MDA) levels, restored the superoxide dismutase (SOD) activity, and increased the protein Nrf2 and HO-1 expression in brain tissues. In primary cultured astrocytes, KBA increased the Nrf2 and HO-1 expression, which provided protection against oxygen and glucose deprivation (OGD)-induced oxidative insult. But knockdown of Nrf2 or HO-1 attenuated the protective effect of KBA. In conclusion, these findings provide evidence that the neuroprotection of KBA against oxidative stress-induced ischemic injury involves the Nrf2/HO-1 pathway.
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: MinChun
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: MingMing
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, China. liyuwenzs@gmail.com.
authors.forename: YuWen
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, China. adwen-2004@hotmail.com.
authors.forename: AiDong
authors.initials: A
authors.lastname: Wen
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D029743:Boswellia / Q000737:chemistry; D001921:Brain / Q000473:pathology; D001925:Brain Damage, Chronic / Q000209:etiology / Q000517:prevention & control; D015687:Cell Hypoxia; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D005947:Glucose / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D008517:Phytotherapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013482:Superoxide Dismutase / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology / Q000633:toxicity*
chemical_list: C447943:11-keto-boswellic acid; D000975:Antioxidants; D051267:NF-E2-Related Factor 2; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; C495637:Nfe2l2 protein, rat; D014315:Triterpenes; D008315:Malondialdehyde; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D013482:Superoxide Dismutase; D005947:Glucose
keywords: 11-Keto-β-boswellic acid; Antioxidants; HO-1; MCAO; Nrf2; Oxygen glucose deprivation