Li Zhuo, Meng Xiangyu, Zhang Jinhui, Feng Na, Shi Cuicui, Zhang Bin
Current Immunology. 2025, 45(5): 555-561.
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The aim of this study was to investigate the therapeutic effect of acacetin on depressed rats and its regulation on the HIF-1α/NLRP3 signaling pathway. A rat model of depression was established, and rats were divided into the model group, the acacia low-dose group, the acacia high-dose group and the acacia high-dose + pathway activator group (acacia high-dose+BMS-986299 group), with 12 rats in each group, in addition to a control group. After the treatment was completed, the sugar water preference, the mine field experiment, and the forced exercise experiment were performed, respectively. ELISA was used to detect levels of inflammatory and oxidative stress factors. H-E and Nissl staining were used to observe the histopathological morphology and neuronal number of hippocampus. Western blotting was used to detect the expression of proteins related to the HIF-1α/NLRP3 signaling pathway. Compared to those of the control group, the hippocampal tissue structure of the model group was damaged, the pyramidal cell arrangement was disordered, the nuclear condensation phenomenon was obvious, and the numbers of Nissl bodies and neurons decreased. In the meantime, the sugar water preference rate, voluntary activity score, and the level of CAT were decreased, whereas the immobility time of forced swimming, the levels of IL-6, IL-β, TNF-α, reactive oxygen species (ROS), malondialdehyde (MDA), and the expression of HIF-1α, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1 were increased (P<0.05). Compared to those of the model group, the hippocampal tissue structure of the acacia low-dose and high-dose groups was relatively normal, and the pyramidal cells were relatively intact and well arranged, the nuclear condensation phenomenon was reduced, and the numbers of Nissl bodies and neurons increased. Consistently, the sugar water preference rate, voluntary activity score, and the level of CAT increased, while the immobility time of forced swimming, the levels of IL-6, IL-β, TNF-α, ROS, MDA, and the expression of HIF-1α, NLRP3, ASC and caspase-1 decreased (P<0.05). Compared to those of the acacia high-dose group, the hippocampal tissue structure damage and pyramidal cell arrangement disorder were aggravated in the acacia high-dose +BMS-986299 group. The nuclear condensation phenomenon was intensified and the numbers of Nissl bodies and neurons decreased. The sugar water preference rate, voluntary activity score, and the level of CAT decreased, while the immobility time of forced swimming, the levels of IL-6, IL-β, TNF-α, ROS, MDA, and the expression of HIF-1α, NLRP3, ASC and caspase-1 were increased (P<0.05). Together, these findings demonstrate that acacetin has therapeutic effect on depression rats, and underlying mechanism is related to the inhibition of the HIF-1α/NLRP3 signaling pathway.
