Abstract：Objective: To investigate the impacts of stachydrine (STA) on neuroprotective ability and Notch signaling pathway in rats with depression. Methods: A depression model rat was constructed and randomly separated into a Model group, a low, medium, and high dose stachydrine groups (STA-L, STA-M, STA-H groups), and a high-dose stachydrine+pathway inhibitor group (STA-H+DAPT group), with 12 rats in each group. Additional 12 healthy rats were selected as the Control group. All rats underwent sugar water preference experiments, forced swimming experiments. Hematoxylin and eosin (H&E) staining was used to evaluated the pathological morphology of hippocampal tissue, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was applied to count the apoptosis of hippocampal neurons. Enzyme-linked immunosorbent assay (ELISA) kits were used to detect levels of neurotransmitters (norepinephrine [NE], dopamine [DA], 5-hydroxytryptamine [5-HT]). Western blot was conducted to recored protein expression related to the Notch signaling pathway. Results: Compared with Control group, the Model group had significantly severe hippocampal tissue damage, high cell apoptosis rate, reduced the proportion of sugar water preference, and prolonged static time in water, reduced neurotransmitters (NE, DA, 5-HT) and Notch1, Hes1, and Jagged1 proteins expression (P<0.05). Compared with the Model group, the STA-L, STA-M, and STA-H groups showed dose-dependent downregulations of degree of hippocampal tissue damage, the cell apoptosis rate, the static time in water, upregulations of sugar water preference, and neurotransmitters levels (NE, DA, 5-HT), Notch1, Hes1, and Jagged1 proteins levels (P<0.05). Compared with the STA-H group, the GAS-H+DAPT group presented more severe damage to the hippocampal tissue in rats, the cell apoptosis rate increased, the proportion of sugar water preference reduced, and the static time in water prolonged, the levels of neurotransmitters (NE, DA, 5-HT) and the expression levels of Notch1, Hes1, and Jagged1 proteins reduced (P<0.05). Conclusion: Stachydrine can improve neuronal damage and enhance neuroprotective function in rats with depression via the regulation of the Notch signaling pathway.
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2025, Vol. 31 
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