Echinacoside alleviates sevoflurane-induced cognitive dysfunction by activating FOXO1-mediated autophagy

Area of Science:

• Neuroscience
• Pharmacology

Background:

• Sevoflurane anesthesia can induce cognitive impairment.
• Understanding the molecular mechanisms underlying anesthesia-induced cognitive deficits is crucial for developing effective interventions.

Purpose of the Study:

• To investigate the therapeutic potential of echinacoside against sevoflurane-induced cognitive impairment in mice.
• To elucidate the role of Forkhead box protein O1 (FOXO1) and autophagy in echinacoside's neuroprotective effects.

Main Methods:

• Mice were exposed to sevoflurane to induce cognitive deficits.
• Echinacoside was administered as a pretreatment.
• FOXO1 was silenced using small interfering RNA (si-FOXO1) in the hippocampus.
• Cognitive function was assessed using behavioral tests (e.g., escape latency, Y-maze).
• Expression levels of FOXO1 and autophagy-related proteins (Beclin 1, ATG5, ATG7, LC3, P62) were analyzed.

Main Results:

• Sevoflurane exposure led to significant cognitive dysfunction in mice.
• Echinacoside pretreatment ameliorated cognitive deficits, improving performance in memory-related tasks.
• Echinacoside increased hippocampal FOXO1 expression and upregulated key autophagy markers (Beclin 1, ATG5, ATG7, LC3) while decreasing P62.
• Silencing FOXO1 exacerbated cognitive impairment and reduced autophagy markers; echinacoside's protective effects were diminished in FOXO1-silenced mice.

Conclusions:

• Echinacoside effectively attenuates sevoflurane-induced cognitive impairment in mice.
• The neuroprotective mechanism involves the upregulation of FOXO1 and the promotion of autophagy in the hippocampus.
• Echinacoside represents a potential therapeutic agent for mitigating anesthesia-related cognitive dysfunction.