Crocetin antagonizes parthanatos in ischemic stroke via inhibiting NOX2 and preserving mitochondrial hexokinase-I.

Parthanatos is one of the major pathways of programmed cell death in ischemic stroke characterized by DNA damage, poly (ADP-ribose) polymerases (PARP) activation, and poly (ADP-ribose) (PAR) formation. Here we demonstrate that crocetin, a natural potent antioxidant compound from Crocus sativus, antagonizes parthanatos in ischemic stroke. We reveal that mechanistically, crocetin inhibits NADPH oxidase 2 (NOX2) activation to reduce reactive oxygen species (ROS) and PAR production at the early stage of parthanatos.