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Hispidulin prevents sevoflurane- Induced memory dysfunction in aged rats.
Biomed Pharmacother. 2018 Jan; 97:412-422.BP

Abstract

AIM

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

Authors+Show Affiliations

Ji'nan Central Hospital Affiliated to Shandong University, Jinan, China.The Fourth People's Hospital of Ji'nan, Jinan, China.Ji'nan Central Hospital Affiliated to Shandong University, Jinan, China. Electronic address: hongnjnsd@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29091891

Citation

Huang, Lubin, et al. "Hispidulin Prevents Sevoflurane- Induced Memory Dysfunction in Aged Rats." Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 97, 2018, pp. 412-422.
Huang L, Huang K, Ning H. Hispidulin prevents sevoflurane- Induced memory dysfunction in aged rats. Biomed Pharmacother. 2018;97:412-422.
Huang, L., Huang, K., & Ning, H. (2018). Hispidulin prevents sevoflurane- Induced memory dysfunction in aged rats. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 97, 412-422. https://doi.org/10.1016/j.biopha.2017.10.142
Huang L, Huang K, Ning H. Hispidulin Prevents Sevoflurane- Induced Memory Dysfunction in Aged Rats. Biomed Pharmacother. 2018;97:412-422. PubMed PMID: 29091891.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hispidulin prevents sevoflurane- Induced memory dysfunction in aged rats. AU - Huang,Lubin, AU - Huang,Kejing, AU - Ning,Hong, Y1 - 2017/11/06/ PY - 2017/08/24/received PY - 2017/10/23/revised PY - 2017/10/24/accepted PY - 2017/11/2/pubmed PY - 2018/8/4/medline PY - 2017/11/2/entrez KW - Hispidulin KW - Memory dysfunction KW - Nrf2 KW - Sevoflurane SP - 412 EP - 422 JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JO - Biomed. Pharmacother. VL - 97 N2 - AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. SN - 1950-6007 UR - https://www.unboundmedicine.com/medline/citation/29091891/Hispidulin_prevents_sevoflurane__Induced_memory_dysfunction_in_aged_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0753-3322(17)34346-9 DB - PRIME DP - Unbound Medicine ER -