The Impacts of Iuteolin on Hippocampal Neuronal Apoptosis in Depressed Mice by Regulating the Nrf2/HO-1/NLRP3 Signaling Pathway
YANG Modi, ZHAI Liang, WANG Yanling, XUE Bin, LIU Qingxia, TIAN Hongmei, ZHANG Jinhui*
The aim of this study was to investigate the impacts of Luteolin on hippocampal neuronal apoptosis and Nrf2/HO-1/NLRP3 (nuclear factor-erythroid 2-related factor 2/heme oxygenase 1/NOD-like receptor thermal protein domain associated protein 3) signaling pathway in mice with depression. In this study, a depression mouse model was constructed, and successfully modeled mice were randomly assigned into a model group, Luteolin-L and Luteolin-H groups, and Luteolin-H+ML385 group (Luteolin-high dose+Nrf2 inhibitor group). Normal healthy mice were also selected as the control group. Then all mice were tested for depression like behavior. ELISA was applied to detect inflammation and oxidative stress levels in hippocampal tissue. HE staining was applied to detect pathological damage in CA3 region of hippocampal tissue. TUNEL staining was applied to detect neuronal apoptosis. Western blot was applied to detect the Nrf2/HO-1/NLRP3 signaling pathway and the expression of apoptosis related proteins. The results showed that compared with the control group, the hippocampal tissue structure in the model group was damaged, neuronal pustular degeneration of neurons appeared, with loose array, hyperchromia of nuclei, partial nucleus fragmentation, blurred or even disappeared nucleolus, and the sugar and water preference index, SOD and GSH levels and the expression of Bcl-2, Nrf2 and HO-1 were decreased. Static time, TNF-α, IL6, IL-β, MDA levels, neuronal apoptosis rate, Bax, NLRP3 expression were increased (P<0.05). Luteolin treatment could improve the pathological injury of hippocampal tissue, increase the sugar water preference index, SOD, GSH levels and the expressions of Bcl-2, Nrf2 and HO-1, decrease the resting time of forced swimming, TNF-α, IL-6, IL-β, MDA levels, neuronal apoptosis rate, Bax and NLRP3 expression (P<0.05). Treatment with ML385, an Nrf2 inhibitor, partially attenuates the effect of luteolin on hippocampal neuron apoptosis in depressed mice. In conclusion, Luteolin can alleviate hippocampal neuronal apoptosis in mice with depression, and its mechanism of action is related to the activation of the Nrf2/HO-1/NLRP3 signaling pathway.
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