Effect of fisetin targeting EGFR/SRC/Bax on improving depressive-like damage and its mechanism

AimTo explore the potential targets and molecular biological mechanisms underlying the antidepressant effects of fisetin.MethodsTargets related to fisetin and depression were screened. CCK-8 assay was used to determine the optimal concentration of corticosterone for inducing a depression model in PC12 cells and the appropriate administration concentration of fisetin. Western blot analysis was employed to assess the expression levels of epidermal growth factor receptor (EGFR), SRC, and Bax proteins in PC12 cells. Immunofluorescence experiments were conducted to observe the localization and expression of EGFR and SRC proteins. Forced swimming test, tail suspension test, and elevated plus maze test were used to evaluate depressive-like behaviors in mice, while HE staining was utilized to observe morphological changes in mouse brain tissue.ResultsCorticosterone significantly upregulated the expression of EGFR, SRC, and Bax proteins in PC12 cells, whereas fisetin intervention notably downregulated the expression levels of these proteins. Compared with the control group, mice in the chronic restraint stress (CRS)model group exhibited pronounced depressivelike behaviors, while these depressive-like impairments were ameliorated in the fluoxetine group and the high- and low-dose fisetin groups.ConclusionFisetin may reduce neuronal damage and ultimately improve depressive-like behaviors in mice by modulating the expression of EGFR/SRC/Bax proteins.