Neuroprotective effects of pinocembrin on ischemia/reperfusion-induced brain injury by inhibiting autophagy.

Background: Cerebral ischemia/reperfusion (I/R) injury is a common pathological process after cardiac arrest, shock and acute cerebral infarction recanalization, which causes serious injury in brain function. Pinocembrin (Pino), a natural flavonoid at the highest concentration in propolis, exhibited a variety of biological effects, including antitumor, antimicrobial and anti-inflammatory activities. However, the effects of Pino on brain injured after I/R and the mechanisms of its neuroprotective effects remain elusive. Methods: In the present study, we used I/R model rats underwent transient cerebral ischemia inducing by four-vessel occlusion and reperfusion. Pino alone or in combination with autophagy inducer rapamycin (RAPA) was administered to I/R rats. The behavior and cognitive function were evaluated by open field test and Morris water maze test. HE staining was used to determine the survival of hippocampus CA1 pyramidal cells. Three key proteins of autophagy, LC3, Beclin1 and p62, were detected by Western blot. Results: Our results showed that Pino could significantly reduce the damage of hippocampus CA1 pyramidal neurons and alleviate the impairments of behavior and cognitive function in I/R rats. Pino also decreased the expression of LC3II and Beclin1 and increased the level of p62 in hippocampus CA1 of I/R rats. In addition, Pino also decreased RAPA-induced neuronal damage and excessive activation of autophagy in I/R rats. Conclusions: Taken together, these results suggested that Pino could protect the brain injury induced by I/R and the potential mechanisms might attribute to inhibition of autophagy activity.