Diallyl disulfide attenuates pyroptosis via NLRP3/Caspase-1/IL-1β signaling pathway to exert a protective effect on hypoxic-ischemic brain damage in neonatal rats

Hypoxic-ischemic encephalopathy (HIE) is a perinatal brain disease caused by hypoxia in neonates. It is one of the leading causes of neonatal death in the perinatal period, as well as disability beyond the neonatal period. Due to the lack of a unified and comprehensive treatment strategy for HIE, research into its pathogenesis is essential. Diallyl disulfide (DADS) is an allicin extract, with detoxifying, Antibacterial, and Cardiovascular Disease protective effects. This study aimed to determine whether DADS can alleviate HIE induced brain damage in rats and oxygen-glucose deprivation (OGD)-induced Pyroptosis in PC12 cells, as well as whether it can inhibit Pyroptosis via the NLRP3/Caspase-1/IL-1β signaling pathway. In vivo, DADS significantly reduced the cerebral infarction volume, alleviated inflammatory reaction, reduced astrocyte activation, promoted tissue structure recovery, improved Pyroptosis caused by HIE and improved the prognosis following HI injury. In vitro findings indicated that DADS increased cell activity, decreased LDH activity and reduced the expression of pyroptosis-related proteins, including IL-1β, IL-18, and certain inflammatory factors in PC12 cells caused by OGD. Mechanistically, DADS inhibited Pyroptosis and protected against HIE via the NLRP3/Caspase-1/IL-1β pathway. The specific inhibitor of Caspase-1, VX-765, inhibited Caspase-1 activation, and IL-1β expression was determined. Additionally, the overexpression of NLRP3 reversed the protective effect of allicin against OGD-induced Pyroptosis. In conclusion, these findings demonstrated that DADS inhibits the NLRP3/Caspase-1/IL-1β signaling pathway and decreases HI brain damage.

Diallyl disulfide; Hypoxic-ischemic brain injury; NLRP3/Caspase-1/IL-1β; Neuroprotection; Pyroptosis.