Exploration of the antidepressant mechanism of Baihe Zhimu decoction based on NLRP1 inflammasome
10.12206/j.issn.2097-2024.202401033
- VernacularTitle:基于NLRP1炎症小体探讨百合知母汤抗抑郁的作用机制
- Author:
Chunhua YUE
1
;
Yongguang BEN
1
;
Haiqiao WANG
2
Author Information
1. School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
2. Department of Traditional Chinese Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 201112, China.
- Publication Type:Originalarticles
- Keywords:
Baihe Zhimu decoction;
Depression;
Inflammatory response;
NLRP1 inflammasome;
BDNF/TrkB signaling pathway
- From:
Journal of Pharmaceutical Practice and Service
2024;42(8):325-333
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the mechanism of antidepressant effect of Baihe Zhimu decoction based on NLRP1 inflammasome. Methods A chronic unpredictable mild stress（CUMS）induced depression mouse model was constructed. C57BL/6J mice were randomly divided into a control group, CUMS group, low-dose Baihe Zhimu decoction group, high-dose Baihe Zhimu decoction group, and MDP group（NLRP1 activator）. After continuous administration for 4 weeks, the behavioral characteristic of mice was investigated. The levels of mice hippocampal inflammatory factors IL-1β、IL-6,TNF-α, and neurotransmitters 5-HT, NE, and DA were detected by ELISA. The expression of inflammasome related proteins NLRP1, ASC, and caspase-1, as well as related proteins in BDNF/TrkB and ERK/AKT/mTOR signaling pathway were detected by Western blot. Immunofluorescence was used to detect changes in BDNF expression in the hippocampus of mice. Results Baihe Zhimu decoction inhibited the activation of NLRP1 inflammasomes in the hippocampus of CUMS mice, improved their behavioral characteristics, increased the level of neurotransmitters in the hippocampus, and reduced the inflammatory response. The NLRP1 activator MDP reversed the above effects of Baihe Zhimu decoction. Baihe Zhimu decoction increased BDNF, TrkB expression, and phosphorylation levels of ERK, AKT, and mTOR proteins, which could be reversed by MDP. Conclusion Baihe Zhimu decoction improved depression like behavior in CUMS mice by inhibiting NLRP1 inflammasome activation and hippocampal neuroinflammatory response, and thereby activating BDNF/TrkB and ERK/AKT/mTOR signaling pathway.
