Ellagic acid alleviates NLRP6/caspase-1/GSDMD-mediated inflammation and pyroptosis in rats post cerebral ischemia/reperfusion injury

Objective(s): Ellagic acid (EA) is a natural polyphenol with anti-cancer, anti-oxidant, anti-inflammatory, antibacterial, and other effects. However, the role of EA in cerebral ischemia/reperfusion injury (CIRI) remains unclear. This study aims to investigate the neuroprotective effects of EA in CIRI.Materials and Methods: Forty male Wistar rats (260-300 g) were randomly divided into four groups with 10 rats per group: 1) Sham+Veh: Rats underwent I/R surgery, except that they were not inserted with thread plugs, and received solute treatment at the same time. 2) MCAO/R+Veh. 3) MCAO/R+EA: Rats were administered 200 mg/kg EA before undergoing MCAO. 4) MCAO/R+Nim: Rats were administered Nim before undergoing MCAO.Results: Cerebral MCAO/R damaged brain tissue, elevated neurological deficit score (P 0.01), cerebral infarction volume (P 0.01), inflammatory cell infiltration (P 0.01), NLRP6, ASC, caspase-1 and GSDMD mRNA level (P 0.01 and P 0.001), NLRP6, caspase-1, GSDMD-N and IL-1β protein level (P 0.01 and P 0.001), and inflammatory cytokines in brain tissue (P 0.01). Prophylactic administration of EA also significantly improved brain tissue damage, reduced neurological deficit score (P 0.01), cerebral infarction volume (P 0.01), inflammatory cell number (P 0.05), NLRP6, caspase-1, GSDMD-N mRNA and protein level (P 0.05 and P 0.01), ASC mRNA level and IL-1β protein level (P 0.01), and IL-1β and IL-18 level in brain tissue (P 0.01) compared to positive control.Conclusion: EA may serve as a potential drug for the treatment of brain I/R, which may exert an anti-inflammatory effect by inhibiting the activation of the inflammasome.