Salidroside alleviates sevoflurane-induced mouse hippocampal neuronal injury by inhibiting ferroptosis&nbsp;

doi:10.13418/j.issn.1001-165x.2026.3.06

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Chinese Journal of Clinical Anatomy ›› 2026, Vol. 44 ›› Issue (3) : 281-289. DOI: 10.13418/j.issn.1001-165x.2026.3.06

Salidroside alleviates sevoflurane-induced mouse hippocampal neuronal injury by inhibiting ferroptosis

Mao Ke, Du Silong, Liu Pengsen, Yang Jiansheng, Zhao Yanfen, Wang Can, Guo Yunliang*

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Abstract

Objective To explore the effect and mechanism of salidroside (SAL) on sevoflurane (SEVO)-induced ferroptosis in mouse hippocampal HT22 cells. Methods The safe concentration of salidroside (50 μmol/L) was screened by MTT assay, and a SEVO-induced HT22 cell injury model was established with 4 groups: control, SEVO, SEVO+SAL and SEVO+SAL+Erastin (a ferroptosis activator). FerroOrange probe was used to detect intracellular iron levels, immunofluorescence was employed to examine GPX4 protein expression, and commercial assay kits were applied to measure GSH, MDA and 4-HNE contents. Lipid ROS levels were detected using C11-BODIPY 581/591. Based on target pathway prediction from SwissTargetPrediction and FerrDb databases, Western blot was performed to detect p-EGFR protein expression to validate pathway activity. Finally, the regulatory role of this pathway in HT22 cell ferroptosis was clarified using the EGFR inhibitor AG1478 and agonist EGF. Results Salidroside significantly improved SEVO-induced reduction in cell viability, inhibited iron accumulation, upregulated GPX4 and GSH levels, and decreased lipid ROS, MDA, and 4-HNE contents (P<0.05). The addition of Erastin partially reversed the protective effect of salidroside (P<0.05). Bioinformatics and experimental verification confirmed that salidroside could inhibit SEVO-induced activation of the EGFR pathway in HT22 cells. AG1478 produced protective effects similar to those of salidroside, whereas activation of this pathway through treatment with EGF significantly attenuated the neuroprotective effects of salidroside (P<0.05). Conclusions Salidroside may attenuate SEVO-induced HT22 cell ferroptosis and neuronal damage by inhibiting EGFR pathway activation, which providing a potential strategy for anesthesia-related neuroprotection.

Key words

Salidroside / / / Hippocampal neurons / / / Sevoflurane / / / Ferroptosis / / / EGFR pathway

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Mao Ke, Du Silong, Liu Pengsen, Yang Jiansheng, Zhao Yanfen, Wang Can, Guo Yunliang. Salidroside alleviates sevoflurane-induced mouse hippocampal neuronal injury by inhibiting ferroptosis [J]. Chinese Journal of Clinical Anatomy. 2026, 44(3): 281-289 https://doi.org/10.13418/j.issn.1001-165x.2026.3.06

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