Journal Article

Posttreatment with 11-Keto-β-Boswellic Acid Ameliorates Cerebral Ischemia–Reperfusion Injury: Nrf2/HO-1 Pathway as a Potential Mechanism

Wang, MingMing, Wen, AiDong, Ding, Yi, Chen, MinChun, Li, YuWen

2015

Overview

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.

• Publisher: Springer US
• Subject: Animals / Antioxidants - pharmacology / Antioxidants - therapeutic use / Apoptosis - drug effects / Astrocytes - drug effects / Astrocytes - metabolism / Biomedical and Life Sciences / Biomedicine / Boswellia - chemistry / Brain - pathology / Brain Damage, Chronic - etiology / Brain Damage, Chronic - prevention & control / Cell Biology / Cell Hypoxia / Cells, Cultured / Drug Evaluation, Preclinical / Glucose - pharmacology / Heme Oxygenase (Decyclizing) - biosynthesis / Heme Oxygenase (Decyclizing) - genetics / Heme Oxygenase (Decyclizing) - physiology / Infarction, Middle Cerebral Artery - drug therapy / Infarction, Middle Cerebral Artery - metabolism / Infarction, Middle Cerebral Artery - pathology / Male / Malondialdehyde - analysis / Nerve Tissue Proteins - biosynthesis / Nerve Tissue Proteins - genetics / Nerve Tissue Proteins - physiology / Neurobiology / Neurology / Neuroprotective Agents - pharmacology / Neuroprotective Agents - toxicity / Neurosciences / NF-E2-Related Factor 2 - biosynthesis / NF-E2-Related Factor 2 - genetics / NF-E2-Related Factor 2 - physiology / Oxidative Stress - drug effects / Phytotherapy / Rats / Rats, Sprague-Dawley / Reperfusion Injury - etiology / Reperfusion Injury - metabolism / Reperfusion Injury - prevention & control / Signal Transduction - drug effects / Signal Transduction - physiology / Superoxide Dismutase - metabolism / Triterpenes - pharmacology / Triterpenes - toxicity