hispidulin and Brain-Ischemia

Ischemia/reperfusion (I/R) injury is the major cause of neurological deficit following stroke. Our previous study showed neuroprotective effects of hispidulin against cerebral ischemia reperfusion injury (IRI). In this study, we further examined the involvement of pyroptosis in this neuroprotective function.. IRI was simulated in a rat model by middle cerebral artery occlusion (MCAO) surgery, and the animals were treated with different doses of hispidulin. The neurological function of the rats was evaluated by the neural function defect score (NFDS), balance beam test and limb placement test. The infarct volume and brain water content were measured 72 h following IRI. Neuronal cell survival and pyroptosis in the ischemic cortex were respectively detected by Nissl staining and TUNEL assay. The relative expression of pyroptosis markers was determined by qRT-PCR, Western blotting and ELISA as appropriate. IRI was simulated in vitro in primary cerebral astrocytes using the OGD/R procedure. AMPKα was blocked genetically or pharmacologically using siRNA and compound C respectively. CCK-8 and LDH release assays were performed using suitable kits.. Hispidulin improved the neurological symptoms of the rats after IRI, in addition to decreasing the infarct size and brain edema. Mechanistically, hispidulin exerted its neuroprotective effects in vivo and in vitro by suppressing NLRP3-mediated pyroptosis by modulating the AMPK/GSK3β signaling pathway.. Hispidulin is a neuroprotective agent with clinical potential against IR-induced neurological injury.

Topics: AMP-Activated Protein Kinases; Animals; Apoptosis; Brain; Brain Ischemia; Cell Survival; Flavones; Glycogen Synthase Kinase 3 beta; Infarction, Middle Cerebral Artery; Male; Neuroprotective Agents; NLR Family, Pyrin Domain-Containing 3 Protein; Pyroptosis; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Signal Transduction; Stroke

Focal cerebral ischemia is associated with ischemia/reperfusion (I/R) injury. Hispidulin is a flavonoid compound with a variety of pharmacological properties. The neuroprotective effects of hispidulin have not been fully elucidated. Herein, we demonstrated that pretreatment of animals with hispidulin improved the neurological outcomes and decreased the infarct size and brain edema in the cerebral focal I/R model. Mechanistically, we showed in vivo and in vitro that hispidulin exerted a protective effect against I/R injury by inducing the Nrf2 antioxidant pathway through modulation of AMPK/GSK3β signaling. Taken together, our results suggest that hispidulin may be a useful neuroprotective agent against ischemia/reperfusion (I/R) injury.

Topics: AMP-Activated Protein Kinase Kinases; Animals; Antioxidants; Brain; Brain Ischemia; Cell Line, Tumor; Flavones; Glycogen Synthase Kinase 3 beta; Humans; Male; Neuroprotective Agents; NF-E2-Related Factor 2; Protein Kinases; Rats; Rats, Wistar; Reperfusion Injury; Signal Transduction