Matairesinol Shows Neuroprotective Activity Against Cerebral Ischemia/Reperfusion Injury via Downregulating TLR4-NLRP3 Inflammasome Pathway

Background: Stroke, a formidable global health issue, is characterized by high disability and mortality rates, thus necessitating advances in acute treatment strategies and preventative medical regimens. Ischemic stroke (IS), the most prevalent type, emerges due to the interruption of blood flow to the brain, resulting in a series of events that may induce irreparable cerebral damage. Objectives: The present work was conducted to study the neuroprotective properties of matairesinol in in vivo and in vitro models. Materials and Methods: The experimental rats were subjected to middle cerebral artery occlusion (MCAO) to induce ischemia/reperfusion (I/R) injury. Rats were pretreated orally with 25 and 50 mg/kg of matairesinol for 7 days earlier to the MCAO. The brain edema, neurological score, and infarction level of the rats were assessed. The concentrations of oxidative stress markers, inflammatory cytokines, and acetylcholinesterase (AChE) concentrations were assessed using kits. The levels of toll-like receptor 4 (TLR4) and NOD-like receptor protein 3 (NLRP3) were also studied using test kits. The in vitro studies were evaluated using oxygen-glucose deprivation/reoxygenation (OGD/R)-stimulated human neuroblastoma cell line (SH-SY5Y) cells. The effect of matairesinol on the viability and inflammatory markers was assessed in OGD/R-stimulated SH-SY5Y cells. Results: The oral pretreatment of matairesinol significantly diminished the brain edema, neurological scores, and infarction level in the rats subjected to MCAO. The matairesinol treatment considerably diminished pro-inflammatory cytokine levels, enhanced antioxidant concentrations, and diminished the AChE in the brain tissues of MCAO-induced rats. Matairesinol treatment also effectively reduced the TLR4 and NLRP3 levels in the brains of MCAO-induced rats. The findings of in vitro studies evidenced that the matairesinol increased viability and reduced inflammatory markers in OGD/R-stimulated SH-SY5Y cells. Conclusion: The research highlighted the neuroprotective property of matairesinol in rats with MCAO-induced cerebral I/R injury. These results may facilitate the advancement of matairesinol as a novel therapeutic agent to treat IS.