Protective effect and mechanism of fruit extracts of Taxus chinensis on hippocampus of chronic unpredictable mild stress rats

The ambitious research aimed to explore the protective impact and mechanism of the ethyl acetate extract of Taxus chinensis fruits (TCFE) on the hippocampi of rats subjected to chronic unpredictable mild stress (CUMS). A total of 32 SD rats were randomly allocated into the control group, model group, TCFE group receiving 200 mg/(kg·d) of TCFE, fluoxetine group receiving 2 mg/(kg·d) of fluoxetine. The rats were induced with chronic unpredictable mild stress (CUMS) for 28 d, and concurrently administered the allocated drugs via gavage for the same duration. The body mass, performance in the open field test (OFT), and sugar-water preference rate of the rats in each group were assessed. The morphology of rat hippocampal tissues was examined using Hematoxylin-Eosin (H&E) staining. Nissl staining was employed to observe hippocampal pathological changes, while ELISA was utilized to measure the levels of IL-1β, TNF-α, IL-6, and IL-18 in the hippocampus. Immunofluorescence was employed to identify the expression of the microglia (MG) marker Iba1 in the rat hippocampus. Furthermore, immunohistochemistry was utilized to detect the expression of Bax and Bcl-2 in the hippocampus. Real-time fluorescence quantitative PCR (qRT-PCR) was utilized to assess the expression levels of two apoptosis-related genes in the rat hippocampus. TUNEL assay was performed to detect tissue cell apoptosis in the rat hippocampus. Finally, Western blotting analysis was conducted to determine the expression of Bax and Bcl-2 proteins in the hippocampus. The consumption of TCFE significantly enhanced body weight ( P < 0.05), sucrose preference rate ( P < 0.05), and total movement distance in the open field test ( P < 0.05). It also improved hippocampal neuronal structure integrity and attenuated loss. Moreover, TCFE regulated the excessive activation of hippocampal microglia in rats, inhibited the expression of IL-1β and TNF-α ( P < 0.05), and modulated the Bax and Bcl-2 expression levels, leading to a significant alteration in the Bax/Bcl-2 ratio ( P < 0.05). TCFE shows promise in attenuating cell apoptosis through the modulation of the Bax/Bcl-2 ratio, suggesting a prospective approach for combating depression.