Autophagy induction by hispidulin provides protection against sevoflurane-induced neuronal apoptosis in aged rats

Sevoflurane is a general anesthetic, which has been found to cause cognitive and memory deficit in elderly. This study is designed to explore the neuroprotective effect of hispidulin, a natural flavone compound, against sevoflurane-induced cognitive dysfunction in aged rats. Human neuroglioma cell line H4 was used as cellular model in our study. The apoptosis of H4 cells was determined by DNA fragmentation and flow cytometry. The autophagy of H4 cells was determined by observing GFP-LC3 II puncta and flow cytometry. The levels of marker proteins for apoptosis and autophagy were determined by western blot. The neuroprotective effect of hispidulin was also examined in aged rat model. The impairment of cognitive function by sevoflurane exposure was evaluated by Morris water maze. The apoptotic cell death in hippocampus was measured by TUNEL assay. Our results showed that hispidulin significantly induced autophagy in H4 cells, which contributed to its protective activity against sevoflurane-induced apoptosis. In addition, our results showed that hispidulin triggered autophagy in AMPK-dependent way. Moreover, the neuroprotective effect hispidulin was verified in aged rat model, which showed that pretreatment with hispidulin significantly attenuated sevoflurane-induced cognitive dysfunction. Meanwhile, our findings revealed that the neuroprotectionin rat model by hispidulin was associated with activation of autophagy and AMPK signaling pathway. The findings in this present study highlight that hispidulin offers neuroprotection against sevoflurane-induced cognitive dysfunction, which is mediated by autophagy induction through activating AMPK signaling. The present study provides novel information about the underlying mechanism for the neuroprotective activity of hispidulin.