Objective: To investigate the rescue effect of procyanidin A1(PCA1) on depressed rat models by inhibiting hippocampal neuron apoptosis. Methods: 40 male Sprague-Dawley rats were randomly divided into four groups: normal control group, chronic unpredictable mild stress(CUMS) group, PCA1 treatment group and PCA1+BMS-986299 group. During the experiment, the general conditions of rats were observed every day. After the administration, the symptoms of euphoria were tested by Sucrose Preference Test, and the loco-motor activity of rats was evaluated by open field test. The Nissl staining were employed to analyze the state of nerve cells, and Western Blotting was used to detect the expressions of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X(Bax), cysteinyl aspartate specific proteinase-8(Caspase-8), nucleotide-binding oligomerization domain leucine-rich repeat and pyrin domain-containing 3(NLRP3), apoptosis-associated speck-like protein(ASC), interleukin-18β(IL-18β) in hippocampal tissues. Results: PCA1 could effectively improve the sucrose preference and loco-motor activity interest in depressive rats. Meanwhile, hippocampal neuron ultra-microstructure distortion could also be ameliorated by PCA1 treatment, along with Bax, Caspase-8, NLRP3, ASC, IL-18β upregulation and Bcl-2 downregulation in CUMS rats hippocampus tissues. However, BMS-986299 could significantly abrogate PCA1 effect on CUMS rats. The protein levels of Caspase-8, NLRP3, ASC, and IL-18β were again up-regulated and the protein level of Bcl-2 was again down-regulated. Conclusion: PCA1 exerts its therapeutic effect by inhibiting the NLRP3-Caspase 8 pathway in the apoptosis pathway, which may be the molecular basis for its therapy in depression. |
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