Bakuchiol ameliorates cerebral ischemia-reperfusion injury by modulating NLRP3 inflammasome and Nrf2 signaling

• Published in: Respiratory physiology & neurobiology Vol. 292; p. 103707
• Main Authors: Xu, Yuewei, Gao, Xiaoming, Wang, Li, Yang, Manqin, Xie, Ruonan
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-10-2021
• Subjects: Animals; Bakuchiol; Brain Edema - drug therapy; Brain Edema - immunology; Brain Edema - metabolism; Brain ischemia; Brain Ischemia - drug therapy; Brain Ischemia - immunology; Brain Ischemia - metabolism; Disease Models, Animal; Infarction, Middle Cerebral Artery - drug therapy; Infarction, Middle Cerebral Artery - immunology; Infarction, Middle Cerebral Artery - metabolism; Inflammasomes - drug effects; Inflammasomes - immunology; Inflammasomes - metabolism; Inflammation; Male; Mice; Mice, Inbred C57BL; Neuroinflammatory Diseases - drug therapy; Neuroinflammatory Diseases - immunology; Neuroinflammatory Diseases - metabolism; NF-E2-Related Factor 2 - drug effects; NLR Family, Pyrin Domain-Containing 3 Protein - drug effects; NLRP3; Nrf2; Phenols - administration & dosage; Phenols - pharmacology; Reperfusion Injury - drug therapy; Reperfusion Injury - immunology; Reperfusion Injury - metabolism; Signal Transduction - drug effects; Brain ischemia; NLRP3; Inflammation; Bakuchiol; Nrf2
• ISSN: 1569-9048; 1878-1519
• DOI: 10.1016/j.resp.2021.103707

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•BAK improved neurological deficit, reduced infarct volume, cerebral edema and neuronal injury in MCAO/R-injured mice.•BAK decreased the number of Iba1-immunoreactive cells in the brain, indicating a reduction of microglial activation.•BAK reduced the expressions of NLRP3, ASC, cleaved-caspase-1, IL-1β and IL-18.•BAK triggered the nuclear accumulation of Nrf2 and elevated HO-1 level.
Cerebral ischemia/reperfusion (I/R) injury is a common cerebrovascular disease with high mortality. Bakuchiol (BAK), extracted from the seeds of psoralea corylifolia, exhibits anti-inflammatory effects on lung, kidney and heart injuries. However, the effect of BAK on brain I/R injury remains elusive. In our study, a cerebral I/R model in mice was established by 1-h middle cerebral artery occlusion and 24-h reperfusion (1-h MCAO/24-h R). Prior to it, mice were gavaged with BAK (2.5 or 5 mg/kg) per day for 5 days. BAK pre-treatment improved neurological deficit, and reduced infarct volume, cerebral edema and neuronal injury in MCAO/R-injured mice. BAK decreased the number of Iba1-immunoreactive cells in the brain, indicating a reduction of microglial activation. BAK also reduced the expressions of NLRP3, ASC, cleaved-caspase-1, IL-1β and IL-18. BAK triggered Nrf2 nuclear accumulation and elevated HO-1 level. Further, the role of BAK was explored in BV-2 microglia with 3-h oxygen-glucose deprivation/24-h reperfusion (3-h OGD/24-h R). It was found that the functions of BAK in vitro were consistent with those in vivo, as manifested by reduced NLRP3 inflammasome and activated Nrf2 signaling. In addition, BV-2 cells were treated with Brusatol, an Nrf2 inhibitor. Results showed that Brusatol partially reversed the protective effect of BAK on OGD/R-injured BV-2 cells, further confirming that BAK might exhibit its anti-inflammatory property via activating Nrf2 signaling. In short, BAK is more meaningful in improving cerebral ischemic injury through suppressing NLRP3-mediated inflammatory response and activating the Nrf2 signaling pathway.