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

## TL;DR

Gyosaponin (GpS) protects rats from sevoflurane-induced brain damage and cognitive issues by activating a key cell survival pathway.

## Contribution

GpS is shown to ameliorate sevoflurane-induced cognitive dysfunction and neuronal apoptosis via the PI3K/AKT/mTOR pathway.

## Key findings

- GpS reduces sevoflurane-induced cognitive deficits and neuronal damage in rats.
- GpS activates the PI3K/AKT/mTOR pathway, which is crucial for its neuroprotective effects.
- Blocking the PI3K/AKT/mTOR pathway reduces the benefits of GpS on cognition and neurons.

## Abstract

•GpS ameliorates Sev-induced cognitive deficits in rats.•GpS ameliorates Sev-induced neuronal cell damage in rats.•GpS promotes activation of the PI3K/AKT/mTOR pathway.•PI3K/AKT/mTOR pathway inhibitor reduces the amelioration of cognitive deficits in Sev-anesthetized rats by high-dose GpS.•PI3K/AKT/mTOR pathway inhibitor impairs the ameliorative effect of high-dose GpS on neuronal cell damage in Sev-anesthetized rats.

GpS ameliorates Sev-induced cognitive deficits in rats.

GpS ameliorates Sev-induced neuronal cell damage in rats.

GpS promotes activation of the PI3K/AKT/mTOR pathway.

PI3K/AKT/mTOR pathway inhibitor reduces the amelioration of cognitive deficits in Sev-anesthetized rats by high-dose GpS.

PI3K/AKT/mTOR pathway inhibitor impairs the ameliorative effect of high-dose GpS on neuronal cell damage in Sev-anesthetized rats.

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.

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.

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.

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