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.

Honokiol ameliorates radiation-induced brain injury via the activation of SIRT3

“… 11 , 12 In this study, we therefore used the SIRT3-activating compound honokiol (HKL) to explore the role of SIRT3 in radioprotection. HKL, also known as 2-(4-hydroxy-3-prop-2-enyl-phenyl)-4-prop-2-enyl-phenol, is a phenolic compound isolated from Magnolia grandiflora that has various properties, 13 including neuroprotective effects. We used a zebrafish model of radiation-induced brain injury because zebrafish are widely used in biomedical research.…”

Inflammasome and Cognitive Symptoms in Human Diseases: Biological Evidence from Experimental Research

“…The inflammasome has been reported to be related to the pathogenesis of PND in various murine models [16,69,77,78]. In a mouse model subjected to anesthesia (isoflurane), aged mice, but not young ones, showed activation of the NLRP3-caspase-1 pathway, poor performance in the Morris water maze, and increased levels of IL-1β and IL-18 [16].…”

“…Surgical operation/anesthesia (sevoflurane) increases the activation of NLRP3 inflammasome, leading to cognitive impairment. Interestingly, it was suggested that increased mitochondrial ROS and malondialdehyde (MDA) production is associated with the NLRP3 inflammasome [78].…”

“…Ac-YVAD-CMK, NF-κB p65 inhibition, and Honokiol contribute to reducing the inflammasome and ameliorating cognitive impairment in PND models [16,77,78]. Ac-YVAD-CMK can attenuate anesthesia (isoflurane)-induced activation of NLRP3 inflammasome in aged brain, thus ameliorating cognitive deficits [16].…”

“…It also reduces long-term potentiation (LTP) deficits and memory impairment [69,77]. Honokiol, a poly phenolic compound, has anti-inflammatory, anti-oxidant, and anti-tumor properties and has shown inhibitory effects on NLRP3 inflammasome and restorative effects on cognitive impairment [78].…”