holothurin-a and Brain-Damage--Chronic

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.

Topics: Animals; Antioxidants; Apoptosis; Astrocytes; Boswellia; Brain; Brain Damage, Chronic; Cell Hypoxia; Cells, Cultured; Drug Evaluation, Preclinical; Glucose; Heme Oxygenase (Decyclizing); Infarction, Middle Cerebral Artery; Male; Malondialdehyde; Nerve Tissue Proteins; Neuroprotective Agents; NF-E2-Related Factor 2; Oxidative Stress; Phytotherapy; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Signal Transduction; Superoxide Dismutase; Triterpenes