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Autophagy induction by hispidulin provides protection against sevoflurane-induced neuronal apoptosis in aged rats.
Biomed Pharmacother. 2018 Feb; 98:460-468.BP

Abstract

AIM

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.

MATERIALS AND METHODS

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.

RESULTS

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.

CONCLUSION

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.

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

29287193

Citation

Huang, Lubin, et al. "Autophagy Induction By Hispidulin Provides Protection Against Sevoflurane-induced Neuronal Apoptosis in Aged Rats." Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 98, 2018, pp. 460-468.
Huang L, Huang K, Ning H. Autophagy induction by hispidulin provides protection against sevoflurane-induced neuronal apoptosis in aged rats. Biomed Pharmacother. 2018;98:460-468.
Huang, L., Huang, K., & Ning, H. (2018). Autophagy induction by hispidulin provides protection against sevoflurane-induced neuronal apoptosis in aged rats. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 98, 460-468. https://doi.org/10.1016/j.biopha.2017.12.097
Huang L, Huang K, Ning H. Autophagy Induction By Hispidulin Provides Protection Against Sevoflurane-induced Neuronal Apoptosis in Aged Rats. Biomed Pharmacother. 2018;98:460-468. PubMed PMID: 29287193.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Autophagy induction by hispidulin provides protection against sevoflurane-induced neuronal apoptosis in aged rats. AU - Huang,Lubin, AU - Huang,Kejing, AU - Ning,Hong, Y1 - 2017/12/27/ PY - 2017/12/01/received PY - 2017/12/19/revised PY - 2017/12/20/accepted PY - 2017/12/30/pubmed PY - 2018/8/16/medline PY - 2017/12/30/entrez KW - AMPK KW - Autophagy KW - Cognitive dysfunction KW - Hispidulin KW - Sevoflurane SP - 460 EP - 468 JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JO - Biomed. Pharmacother. VL - 98 N2 - AIM: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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. SN - 1950-6007 UR - https://www.unboundmedicine.com/medline/citation/29287193/Autophagy_induction_by_hispidulin_provides_protection_against_sevoflurane_induced_neuronal_apoptosis_in_aged_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0753-3322(17)36505-8 DB - PRIME DP - Unbound Medicine ER -