Honokiol-Mediated Mitophagy Ameliorates Postoperative Cognitive Impairment Induced by Surgery/Sevoflurane via Inhibiting the Activation of NLRP3 Inflammasome in the Hippocampus.

Abstract

BACKGROUND:

The potential mechanism of postoperative cognitive impairment is still largely unclear. The activation of NLRP3 inflammasome had been reported to be involved in neurodegenerative diseases, including postoperative cognitive change, and is closely related to mitochondrial ROS and mitophagy. Honokiol (HNK) owns multiple organic protective effects. This study is aimed at observing the neuroprotective effect of HNK in postoperative cognitive change and examining the role of HNK in the regulation of mitophagy and the relationship between these effects and NLRP3 inflammasome activation in mice induced by surgery/anesthesia.

METHODS:

In this study, mice were divided into several groups: control group, surgery group, surgery+HNK group, and surgery+HNK+3-methyladenine (3-MA) group. Hippocampal tissue samples were harvested and used for proinflammatory cytokines, mitochondrial ROS, and malondialdehyde (MDA) assay. The process of mitophagy and the activation of NLRP3 inflammasome were observed by Western blot, immunohistochemistry, and transmission electron microscopy.

RESULTS:

The results showed that HNK treatment obviously recovered the postoperative decline and enhanced the expressions of LC3-II, Beclin-1, Parkin, and PINK1 at protein levels after surgery/sevoflurane treatment, which are both an autophagy marker and a mitophagy marker. In addition, HNK attenuated mitochondrial structure damage and reduced mtROS and MDA generation, which are closely associated with NLRP3 inflammasome activation. Honokiol-mediated mitophagy inhibited the activation of NLRP3 inflammasome and neuroinflammation in the hippocampus. Using 3-MA, an autophagy inhibitor, the neuroprotective effects of HNK on mitophagy and NLRP3 inflammasome activation were eliminated.

CONCLUSION:

These results indicated that HNK-mediated mitophagy ameliorates postoperative cognitive impairment induced by surgery/sevoflurane. This neuroprotective effect may be involved in inhibiting the activation of NLRP3 inflammasome and suppressing inflammatory responses in the hippocampus.

• Authors: Ji-Shi Ye, Lei Chen, Ya-Yuan Lu, Shao-Qing Lei, Mian Peng, Zhong-Yuan Xia
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2019 Pg. 8639618 ( 2019) ISSN: 1942-0994 [Electronic] United States
• PMID: 30918581 (Publication Type: Journal Article)

Chemical References

• Biphenyl Compounds
• Inflammasomes
• Lignans
• NLR Family, Pyrin Domain-Containing 3 Protein
• Reactive Oxygen Species
• honokiol
• Sevoflurane

Topics

• Animals
• Apoptosis (drug effects)
• Autophagy (drug effects)
• Biphenyl Compounds (pharmacology, therapeutic use)
• Cognitive Dysfunction (drug therapy, etiology)
• Dentate Gyrus (metabolism, pathology)
• Female
• Hippocampus (metabolism, ultrastructure)
• Inflammasomes (metabolism)
• Lignans (pharmacology, therapeutic use)
• Mice, Inbred C57BL
• Microglia (drug effects, metabolism)
• Mitochondria (drug effects, metabolism, ultrastructure)
• Mitophagy (drug effects)
• NLR Family, Pyrin Domain-Containing 3 Protein (metabolism)
• Neurons (drug effects, pathology)
• Oxidative Stress (drug effects)
• Postoperative Complications (drug therapy, etiology)
• Reactive Oxygen Species (metabolism)
• Sevoflurane (adverse effects)