Litebamine ameliorates cerebral ischemia-induced blood-brain barrier damage by inhibiting pyroptosis

OBJECTIVE: Stroke continues to be a significant global health concern, ranking as the second leading cause of death worldwide. This study aimed to investigate the potential neuroprotective effects of Litebamine (Lite), an alkaloid from Litsea cubeba, on blood-brain barrier (BBB) integrity and neurological function in ischemic stroke models. METHODS: Using a MCAO/R mouse model, we assessed the effects of Lite on neurological deficits, cerebral blood flow, and infarct volume. BBB integrity was evaluated using Evans blue staining and Western blot analysis of tight junction proteins and pyroptosis-associated protein levels. Additionally, in vitro studies with bEnd.3 cells under OGD/R conditions were conducted to evaluate cell viability, matrix metalloproteinases expression, and pyroptosis-associated protein levels. RESULTS: Lite treatment significantly reduced neurological deficit scores and infarct volume in MCAO/R mice. Lite also restored cerebral blood flow and improved BBB integrity by upregulating ZO-1 and Occludin while downregulating MMP-2 and MMP-9. In vitro studies indicated that Lite exhibited protective effects on bEnd.3 cells under OGD/R conditions. Additionally, Lite inhibited NLRP3 inflammasome activation and pyroptosis-associated proteins (ASC, C-GSDMD, C-caspase1), reducing IL-1β and IL-18 levels both in vivo and in vitro. CONCLUSION: Lite ameliorates cerebral ischemia-induced blood-brain barrier damage by inhibiting NLRP3-mediated pyroptosis in endothelial cells.