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Morroniside ameliorates sevoflurane anesthesia-induced cognitive dysfunction in aged mice through modulating the
Jianxing Chen1, Bo Peng2, Wenqian Lin3
1Department of Anesthesiology, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China; Department of Anesthesiology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China; Anesthesiology Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Abstract:
Morroniside (Mor) is a bioactive compound in Cornus officinalis with anti-inflammatory, neuroprotective and antioxidant properties. Prolonged use of the anesthetic sevoflurane (Sev) has been connected to the development postoperative cognitive dysfunction (POCD). This research aims to elucidate the mechanism of action of Mor to improve cognitive impairment. A model of cognitive dysfunction induced by Sev was established in aged mice and tested for behavioral analysis using the water maze experiment. Histopathological changes and neuronal apoptosis in mouse hippocampus were observed by hematoxylin and eosin (HE) staining, Nissl staining, and TUNEL staining. ELISA and qRT-PCR determined the levels of inflammatory factors. Phenotypic transformation of microglia in hippocampal tissue was assessed by immunofluorescence, flow cytometry, and qRT-PCR. The interaction between Mor and TLR4 was analyzed using molecular docking. Western blot identified the levels of apoptosis-related proteins, synapse-related proteins, and TLR4/NF-κB pathway proteins. Inhalation of Sev caused a notable reduction in learning and spatial memory in old mice, which was dose-dependently ameliorated by Mor. Mor inhibited neuroinflammation, modulated the polarization state of hippocampal microglia, promoted their polarization to M2 type, alleviated Sev-induced hippocampal tissue damage and neuronal apoptosis. Notably, Mor can bind well with TLR4 and reduce TLR4-positive expression. Mor blocked Sev-induced TLR4/NF-κB pathway activation in hippocampal tissues, and the TLR4 agonist CRX-527 attenuated the effect of Mor. In conclusion, Mor blocked the TLR4/NF-κB pathway, reducing hippocampal tissue damage and neuroinflammation caused by Sev, which in turn improving cognitive impairment in aged mice.
Insights
Morroniside (Mor) improves cognitive impairment in aged mice by blocking the TLR4/NF-κB pathway. This action reduces neuroinflammation and hippocampal damage caused by sevoflurane (Sev) anesthesia.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Prolonged sevoflurane (Sev) anesthesia can lead to postoperative cognitive dysfunction (POCD) in aged individuals.
- Morroniside (Mor), a compound from Cornus officinalis, exhibits anti-inflammatory, neuroprotective, and antioxidant effects.
- Understanding Mor's mechanism against Sev-induced cognitive impairment is crucial for therapeutic development.
Purpose of the Study:
- To investigate the protective mechanism of Mor against sevoflurane-induced cognitive dysfunction in aged mice.
- To elucidate Mor's effects on neuroinflammation, neuronal apoptosis, and microglial activation in the hippocampus.
- To determine Mor's interaction with the TLR4/NF-κB signaling pathway.
Main Methods:
- Sevoflurane-induced cognitive dysfunction model in aged mice.
- Behavioral analysis using the water maze test.
- Histopathological examination (HE, Nissl, TUNEL staining) of hippocampal tissue.
- ELISA and qRT-PCR for inflammatory factors and microglial polarization.
- Molecular docking, Western blot, and immunofluorescence for pathway analysis.
Main Results:
- Sevoflurane significantly impaired learning and memory, which Mor dose-dependently improved.
- Mor reduced hippocampal neuroinflammation, neuronal apoptosis, and modulated microglial polarization towards M2 phenotype.
- Mor demonstrated binding affinity with TLR4, reduced its expression, and inhibited the TLR4/NF-κB pathway activation.
- The TLR4 agonist CRX-527 counteracted Mor's protective effects, confirming pathway involvement.
Conclusions:
- Morroniside effectively ameliorates sevoflurane-induced cognitive impairment in aged mice.
- The protective effects are mediated by inhibiting the TLR4/NF-κB pathway, reducing neuroinflammation and apoptosis.
- Mor modulates microglial activation and protects hippocampal tissue, offering a potential therapeutic strategy for POCD.
