Effects of modified Xiaoyao San on TLR4/NF-κB pathway in hippocampal microglia of LPS-induced depression model rats

doi:10.12047/j.cjap.5936.2020.076

Abstract

Abstract: Objective: To investigate the effects of modified Xiaoyao San on TLR4/NF-κB pathway in hippocampal microglia of LPS-induced depression model rats, and to explore its antidepressant mechanism. Methods: SD rats were randomly divided into control, model, fluoxetine (10 mg·kg^-1), low and high dose of modified Xiaoyao San (3.64, 7.28g·kg^-1) group. The depression model was established by chronic LPS injection (ip, 0.5 mg·kg^-1) and rats were treated by intragastric administration for 14 days. After the model was established, the depression-like behavior of rats was evaluated by open field and forced swimming test. The expression of microglia marker protein Iba-1 was detected by immunohistochemistry. The levels of TNF-α and IL-6 in hippocampal homogenate were detected by ELISA method and the expressions of TLR4 and NF-κB protein in hippocampus were detected by Western blot. Results: Compared with control group, the depression-like behavior was significant in model group rats (P＜0.01), the microglia in the brain was activated (P＜0.01), the contents of TNF-α and IL-6 in the hippocampus were increased (P＜0.01), and the expression levels of TLR4 and NF-κB proteins were up-regulated (P＜0.01). Compared with model group, the depression-like behavior of the rats in the fluoxetine and high-dose modified Xiaoyao San group was significantly alleviated (P＜0.05), the expression of Iba-1 in microglia returned to normal (P＜0.01), the contents of TNF-α and IL-6 were decreased (P＜0.01), and the expression levels of TLR4 and NF-κB protein were decreased (P＜0.05). Compared with fluoxetine group, the high-dose modified Xiaoyao San group had no statistically significant difference in each index, suggesting that there was no significant difference in the antidepressant effect between the two groups. Conclusion: Modified Xiaoyao San can significantly improve the depression-like behavior in rats, and its mechanism may be related to inhibiting the TLR4/NF-κB pathway of microglia and down-regulating the expression of inflammatory factors.

Key words: depression, modified Xiaoyao San, LPS, microglia, TLR4/NF-κB, rat

CLC Number:

R277.7

GUO Rui, QIN Wei-shuai, ZHANG Shuang-yong, ZHANG Shu-ling. Effects of modified Xiaoyao San on TLR4/NF-κB pathway in hippocampal microglia of LPS-induced depression model rats[J]. CJAP, 2020, 36(4): 354-357.

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