cPKCγ membrane translocation is involved in herkinorin-induced neuroprotection against cerebral ischemia/reperfusion injury in mice

Abstract

Herkinorin is an opiate analgesic with limited adverse effects, functioning as a primary selective atypical opioid µ agonist. The present study aimed to identify whether herkinorin has a positive effect on ischemic/reperfusion (I/R) injury. Adult male C57BL/6 mice were randomly divided into five groups: i) Naïve, ii) sham, iii) I/R, iv) I/R with dimethyl sulfoxide (I/R+D) and v) I/R with herkinorin (I/R+H). The I/R injury model was induced by occluding the middle cerebral artery for 1 h followed by 24 h or 7 days of reperfusion. Neurobehavioral scores and sensorimotor functions were examined 24 h and 7 days following reperfusion. In addition, infarct volumes were examined at these time points using a 2,3,5-triphenyltetrazolium chloride assay. Herkinorin treatment improved neurobehavioral and sensorimotor functional recovery from I/R-induced brain injury. There was a significant decrease in infarct volume in the I/R+H group at 24 h or 7 days following reperfusion compared with the I/R and I/R+D groups. Western blotting suggested that the decrease in conventional protein kinase C γ (cPKCγ) membrane translocation in the peri-infarct region may be attenuated by herkinorin pretreatment. These results indicated that herkinorin may be beneficial in I/R-induced mouse brain injury, and this may be attributed to the membrane translocation of cPKCγ following activation.

Herkinorin negatively regulates NLRP3 inflammasome to alleviate neuronal ischemic injury through activating Mu opioid receptor and inhibiting the NF‐κB pathway

“…10 Our previous study showed that Herkinorin treatment decreased cerebral infarct volume and improved neurobehavioral and sensorimotor functional recovery at 24 h or 7 days following transient middle cerebral artery occlusion/ reperfusion in mouse. 11 We hope to explore further the effect of Herkinorin on regulating NLRP3-mediated inflammatory response in cerebral I/H injury, as well as the type of opioid receptors and molecular mechanisms.…”