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

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-113 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 oxygenglucose 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 antiinflammatory 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.

Automated summary

This study showed that pretreatment with BAK could improve neurological deficits, reduce infarct volume, cerebral edema, and neuronal injury in MCAO/R-injured mice. The protective effect of BAK may be attributed to its ability to suppress NLRP3-mediated inflammatory response and activate the Nrf2 signaling pathway.