Cucurbitacin B alleviates cerebral ischemia/reperfusion injury by inhibiting NLRP3 inflammasome-mediated inflammation and reducing oxidative stress

Cucurbitacin B (CuB) has been demonstrated to possess anti-inflammatory and antioxidative properties. However, the effect of CuB on cerebral ischemia/reperfusion (I/R) injury was unclear. In this work, we found that CuB significantly elevated cell viability, decreased lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) production, and proinflammatory factor levels in oxygen-glucose deprivation/reoxygenation-exposed PC12 cells, reduced cerebral infarction volume and neuronal apoptosis, inhibited oxidative stress and inflammation, and improved neurological function in mice with middle cerebral artery occlusion-induced cerebral I/R injury. Meanwhile, CuB decreased levels of NLRP3, cleaved caspase-1, and cleaved interleukin-1 beta, which were upregulated by I/R injury. Moreover, upregulation of NLRP3 dramatically reversed the effects of CuB on NLRP3 inflammasome activation, cell viability, and levels of proinflammatory factors in vitro. In conclusion, this study demonstrated that CuB attenuated cerebral I/R injury by inhibiting NLRP3 inflammasome-mediated inflammation and reducing oxidative stress.