Gyosaponin ameliorates sevoflurane anesthesia-induced cognitive dysfunction and neuronal apoptosis in rats through modulation of the PI3K/AKT/mTOR pathway

Lijuan Lin; Chenhui Zhu; Bing Yan; Pinxian Yu; Liu Yang; Wei Huang; Junren Chen

doi:10.1016/j.clinsp.2024.100560

Gyosaponin ameliorates sevoflurane anesthesia-induced cognitive dysfunction and neuronal apoptosis in rats through modulation of the PI3K/AKT/mTOR pathway

Clinics (Sao Paulo). 2024 Dec 20:80:100560. doi: 10.1016/j.clinsp.2024.100560. Online ahead of print.

Authors

Lijuan Lin¹, Chenhui Zhu², Bing Yan¹, Pinxian Yu¹, Liu Yang¹, Wei Huang¹, Junren Chen³

Affiliations

¹ Department of Anesthesia, Central People's Hospital of Zhanjiang, Zhanjiang City, Guangdong Province, PR China.
² Department of Urology, Central People's Hospital of Zhanjiang, Zhanjiang City, Guangdong Province, PR China.
³ Department of Anesthesia, Central People's Hospital of Zhanjiang, Zhanjiang City, Guangdong Province, PR China. Electronic address: JunrenChencc@outlook.com.

PMID: 39708584
DOI: 10.1016/j.clinsp.2024.100560

Abstract

Background: Sevoflurane (Sev) is an inhalational anesthetic for surgical procedures where it can trigger cognitive dysfunction and neuronal apoptosis. Gyosaponin (GpS) was studied for its effects on brain morphology and cognitive behaviors in Sev-anesthetized rats.

Methods: Male Sprague-Dawley rats were induced by 3 % Sev anesthesia, and 25 mg/kg and 100 mg/kg GpS were injected into the rats by tail vein. The in vitro model of Sev anesthesia was constructed by treating primary rat hippocampal neurons with 4.1 % Sev in the presence of GpS (5, 10, and 20 μM). The neuroprotective effects of GpS against Sev-induced cognitive deficits in rats were evaluated using the open field and Morris water maze tests. The apoptosis of hippocampal neurons was observed using HE staining and TUNEL assay. Apoptosis-related proteins and proteins related to the PI3K/Akt/mTOR pathway were determined via Western blot. Also, pro-inflammatory factors were measured via ELISA.

Results: GpS diminished the Sev-triggered apoptosis in neurons and Cleaved caspase-3, BAX, TNF-α, IL-6, lessened oxidative stress damage, and stimulated the PI3K/Akt/mTOR pathway. GpS therapy markedly enhanced learning and memory abilities in rats suffering from Sev-related cognitive impairments.

Conclusion: GpS ameliorates Sev-induced neurotoxicity and cognitive dysfunction by modulating the PI3K/Akt/mTOR pathway and alleviating neuronal apoptosis and oxidative stress.

Keywords: Cognitive Dysfunction; Gyosaponin; Neuronal Cell Apoptosis; PI3K/AKT/mTOR Pathway; Sevoflurane.