Hydroxysafflor Yellow A Ameliorates Ischemic Stroke by Inhibiting NLRP3, AIM2, and Pyrin Inflammasome-Mediated...

Hydroxysafflor Yellow A (HSYA), a water-soluble compound derived from the traditional Chinese medicine Carthamus tinctorius L., is known for its protective effects against cerebral ischemia/reperfusion(I/R) injury, though its mechanism remains unclear. This study investigated the effect of HSYA on cerebral I/R injury and its potential relation to pyroptosis. Adult male Sprague-Dawley rats were divided into sham-operated, model, and HSYA-treated groups. HSYA was administered as a pretreatment for 5 days before constructing the cerebral I/R injury model. Neurological function scores, TTC staining, HE staining, Nissl staining, immunofluorescence staining, SOD, GSH, GSH-Px, MDA, LDH Assays, PCR, western blotting, and ELISA were used to assess HSYA's effects. HSYA pretreatment improved neurological deficits and pathological state of brain tissue and reduced infarct area. It raised SOD, GSH, and GSH-Px activities, along with reduced MDA and LDH levels. Immunofluorescence staining and western blotting revealed that HSYA effectively inhibited the expression of NLRP3, AIM2, Pyrin, Cleaved-Caspase1, GSDMD, ASC, and HMGB1-related proteins. Additionally, ELISA results demonstrated that HSYA suppressed the release of IL18 and IL-1β inflammatory factors in serum. These findings suggest HSYA may alleviate ischemic stroke injury by inhibiting NLRP3, AIM2, and Pyrin inflammasome-mediated pyroptosis, offering a potential therapeutic strategy for cerebral I/R injury.