Studies have found that
Platonin has
neuroprotective effect, but its molecular mechanism needs further study. We found that at the early stage of
cerebral ischemia/
reperfusion injury,
Platonin treatment significantly reduced
cerebral infarct lesions, improved neurological scores, and exerted
neuroprotective effects. Our group has shown that NLRP3
inflammasomes activation is required to mediate neuronal injury during
cerebral ischemia /
reperfusion injury. The brain protective effect of
Platonin is related to its ability to effectively regulate autophagy and NLRP3
inflammasomes-derived
inflammation.
Platonin treatment effectively induced autophagy (LC3II/I, p62) and reduced NLRP3
inflammasomes activation(NLRP3, cleaved-IL-1β,cleaved-IL-18, cleaved-caspase1). However, 3-MA (15 mg/kg) treatment downregulated the inhibitory effect of
Platonin on NLRP3
inflammasomes. We also studied the location of BNIP3 in
Platonin-mediated neuroprotection and found that
Platonin induced the expression of autophagic
protein BNIP3 and enhanced the co-immunoprecipitation of BNIP3 with LC3, and double-labeled immunofluorescence also showed enhanced co-localization of BNIP3 with LC3. Finally, si-BNIP3 transfection attenuated the co localization of BNIP3 with LC3, decreased the autophagy activity to a certain extent and blocked the inhibition of NLRP3
inflammasomes-derived
inflammation by
Platonin. This study demonstrated that
Platonin may play a neuroprotection role in cerebral I / R injury by inhibiting NLRP3
inflammasomes activation through upregulating autophagy via BNIP3 / LC3 pathway.