Inhibition of the JAK2/STAT3 Signaling Pathway by Piperine Confers Neuroprotection in Rats with Ischemic Stroke

Abstract

Abstract Pepper is a traditional Chinese herbal medicine used for different inflammatory, fever, and bacterial infections. Our previous research shown that the principal pepper active component, piperine, reduces cerebral ischemia-reperfusion (I/R) damage, but the underlying mechanism was not completely understood. In this study, SH-SY5Y cells and Sprague–Dawley rats were pretreated with piperine, AG490, or vehicle. Oxygen–glucose deprivation of SH-SY5Y cells and a rat middle cerebral artery occlusion model were used to mimic cerebral I/R injury. In vitro results from CCK-8 and LDH assays showed that piperine and AG490 mitigated I/R injury induced by OGD and WB showed that piperine lowered the levels of p-JAK2 and p-STAT3. The infarction volume and neuronal apoptosis were reduced by piperine and AG490 in vivo, as demonstrated by TTC, HE, and TUNEL staining. The mNSS, beam-walking test, and MST test indicated that piperine and AG490 promoted recovery of neurological function after I/R injury in rats. These in vivo and in vitro findings demonstrate that the neuroprotective action of piperine on brain I/R injury is mediated by the JAK2/STAT3 signal pathway. It offers a viable therapeutic target for cerebral I/R injury and piperine could be turned into a potential JAK2-specific inhibitor.