Periplaneta americana (L.) Extract PAS840 Promotes Ischemic Stroke Recovery by Inhibiting Inflammasome Activation

Simple SummaryIschemic stroke (IS) is a high-mortality cardiovascular disease. This study analyzedPeriplaneta americana(L.) extract (PAS840) components using LC-MS/MS and peptidomics, and predicted its IS-related therapeutic targets by network pharmacology. In BV-2 cells after OGD/R injury, multiple techniques explored PAS840’s effects on cell functions and pathways. In a tMCAO rat model, various methods evaluated its impact on the blood–brain barrier, inflammation, and neural function. Results show PAS840 can act on multiple IS-related pathways. It inhibits the NLRP3 inflammasome pathway in BV-2 cells, reduces oxidative stress, inflammation, and pyroptosis, and improves cell viability. In tMCAO rats, it can reduce the NLRP3 inflammasome pathway, activate growth factor pathways, and protect the blood–brain barrier. These findings suggest that PAS840 is a promising drug worthy of development for the treatment of IS.Ischemic stroke (IS) is a high-mortality, multi-complication cardiovascular disease. Reducing brain injury and promoting neuronal repair after IS onset remain important challenges for current treatments. Our team previously found that PAS840, an extract fromPeriplaneta americana(L.), protects nerve function; this study further uses LC-MS/MS and peptidomics to analyze PAS840’s components and network pharmacology to predict its ischemic stroke (IS) therapeutic targets. We then employed Transwell, a biochemical kit, real-time quantitative polymerase chain reaction (RT-qPCR), and transcriptomics to investigate PAS840’s effects on migration ability, oxidative stress levels, and cellular pathways in mouse microglial cells (BV-2) following oxygen–glucose deprivation/reoxygenation (OGD/R) injury. Finally, using Evans blue staining, immunohistochemical analysis, and RT-qPCR, we investigated PAS840’s effects on the blood–brain barrier, inflammation pathways, and neural function in a transient middle cerebral artery occlusion (tMCAO) rat model. PAS840 components target multiple IS pathways, effectively inhibit NF-κB/NLRP3/Caspase-1/IL-1β inflammasome pathway activation in BV-2 cells following OGD/R, reduce cellular oxidative stress, inflammation, and pyroptosis, and improve cell viability and migration ability. PAS840 decreases NF-κB/NLRP3/Caspase-1/IL-1β inflammasome pathway expression in tMCAO rat brains, reduces inflammation, activates BDNF/VGF/NGR1/Erbb4 neurotrophic factor and vascular endothelial growth factor pathways, enhances neuronal cell viability, and effectively protects and repairs the blood–brain barrier.