hispidulin and Memory-Disorders

As a widely used general anesthetic, sevoflurane has been found to induce cognitive and memory defectsin the elderly. This may increase the risk of Alzheimer's disease. This study explores the neuroprotective effect of hispidulin, a natural flavone compound, against sevoflurane-induced memory dysfunction.. The effect of sevoflurane exposure on memory function was evaluated by novel object recognition and Y-maze testing using an aged rat model. The apoptotic cell death in the hippocampus of rats was assessed using a TUNEL assay. The levels of protein markers for cell apoptosis in the hippocampus were examined by western blot. The effect of sevoflurane and hispidulin on the accumulation of Aβ was also examined. In addition, the attenuating effect of hispidulin on sevoflurane-induced neuroinflammation was assessed by measuring the expression of pro-inflammatory cytokines and the translocation of NF-κB p65 from cytosol to nucleus. The activation of Nrf2 in the hippocampus was also detected. Moreover, the effect of hispidulin on sevoflurane-induced apoptosis, Aβ accumulation, and neuroinflammation was also examined in human neuroglioma H4 cells, which served as an in vitro model.To further examine the role of Nrf2 in the neuroprotective activity of hispidulin against sevoflurane-neurotoxicity, H4 cells were transfected with Nrf2 targeting siRNA, which led to a significant reduction in Nrf2 expression.. Both novel object recognition and Y-maze testing showed that sevoflurane significantly impaired the memory of aged rats, which was significantly reversed by pretreatment with hispidulin. Mechanistically, our findings revealed that hispidulin significantly attenuated sevoflurane-induced apoptotic cell death, Aβ accumulation, and neuroinflammation. In agreement with in vivo studies, hispidulin was also able to attenuate sevoflurane-induced apoptosis, increases of Aβ levels, and neuroinflammation in H4 cells. Moreover, our results showed that Nrf2 activation mediated the neuroprotective effect of hispidulin against sevoflurane-induced neurotoxicity by demonstrating that knockdown of Nrf2 in H4 cells significantly compromised its protective effects.. As our study provides in vitro and in vivo evidence that hispidulin can offer protection against sevoflurane-induced neurological dysfunction, hispidulin has the potential to be a neuroprotective agent that can improve the cognitive and memory function of elderly patients undergoing anesthesia.

Topics: Aging; Anesthetics, Inhalation; Animals; Apoptosis; Flavones; Male; Memory Disorders; Methyl Ethers; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Sevoflurane

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.

Topics: Anesthetics, Inhalation; Animals; Apoptosis; Autophagy; Cell Line, Tumor; Flavones; Hippocampus; Humans; Male; Memory Disorders; Methyl Ethers; Mitogen-Activated Protein Kinases; Neurons; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Sevoflurane; Signal Transduction