Ellagic acid alleviates NLRP۶/caspase-۱/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 (۲۶۰-۳۰۰ g) were randomly divided into four groups with ۱۰ rats per group: ۱) Sham+Veh: Rats underwent I/R surgery, except that they were not inserted with thread plugs, and received solute treatment at the same time. ۲) MCAO/R+Veh. ۳) MCAO/R+EA: Rats were administered ۲۰۰ mg/kg EA before undergoing MCAO. ۴) MCAO/R+Nim: Rats were administered Nim before undergoing MCAO.Results: Cerebral MCAO/R damaged brain tissue, elevated neurological deficit score (P<۰.۰۱), cerebral infarction volume (P<۰.۰۱), inflammatory cell infiltration (P<۰.۰۱), NLRP۶, ASC, caspase-۱ and GSDMD mRNA level (P<۰.۰۱ and P<۰.۰۰۱), NLRP۶, caspase-۱, GSDMD-N and IL-۱β protein level (P<۰.۰۱ and P<۰.۰۰۱), and inflammatory cytokines in brain tissue (P<۰.۰۱). Prophylactic administration of EA also significantly improved brain tissue damage, reduced neurological deficit score (P<۰.۰۱), cerebral infarction volume (P<۰.۰۱), inflammatory cell number (P<۰.۰۵), NLRP۶, caspase-۱, GSDMD-N mRNA and protein level (P<۰.۰۵ and P<۰.۰۱), ASC mRNA level and IL-۱β protein level (P<۰.۰۱), and IL-۱β and IL-۱۸ level in brain tissue (P<۰.۰۱) 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.

کلیدواژه ها:

Cerebral ischemia/reperfusion injury ، Ellagic acid ، Inflammation ، NLRP۶ inflammasome ، Pyroptosis