Nootkatone Improves Chronic Unpredictable Mild Stress-Induced Depressive-Like Behaviors by Repressing NF-κB/NLRP3-Mediated Neuroinflammation.
10.1007/s11655-022-3725-2
- Author:
Xin-Hua ZHAO
1
;
Na AN
2
;
Meng-Huan XIA
1
;
Wen-Ping LIU
1
;
Qing-Qi WANG
1
;
Ji-Zhang BAO
3
Author Information
1. Basic Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
2. Geriatrics Department, Shanghai Mental Health Center, Shanghai, 200030, China.
3. Hematological Department, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, China. baojizhang@shutcm.edu.cn.
- Publication Type:Journal Article
- Keywords:
NOD-like receptor 3;
depressive disorder;
nootkatone;
nuclear factor-κB;
nuroinflammation
- From:
Chinese journal of integrative medicine
2023;29(1):37-43
- CountryChina
- Language:English
-
Abstract:
OBJECTIVE:To explore the effect of nootkatone (NKT) on chronic unpredictable mild stress (CUMS)-induced depressive-like behaviors and the mechanism underlying NKT improving the depressive-like behaviors.
METHODS:The CUMS-induced depression model was established in mice. Fifty mice were randomized into 5 groups (n=10) in accordance with a random number table: control group, CUMS group, CUMS + NKT (6 mg/kg) group, CUMS + NKT (12 mg/kg) group, and CUMS + ketamine group. From the 22th day, NKT (6 or 12 mg/kg) or ketamine (0.5 mg/kg) was given with intragastric administration every day for 21 days. Behavioral tests including forced swimming test (FST), tail suspension test (TST), sucrose preference test (SPT) and open-field test (OFT) were carried out. The mRNA and protein expressions of interleukin (IL)-1β, IL-18, IL-6, and tumor necrosis factor (TNF)-α in hippocampus were assessed using quantitative realtime polymerase chain reaction (PCR), Western blot analysis, and enzyme linked immunosorbent assay. The nuclear factor-κB (NF-κB)/NOD-like receptor 3 (NLRP3) inflammasome pathway was analyzed using Western blot and immunofluorescence analysis.
RESULTS:NKT treatment improved CUMS-induced depressive-like behaviors in mice (P<0.05 or P<0.01). NKT significantly decreased the mRNA and protein levels of IL-1β, IL-18, IL-6, and TNF-α in hippocampus of CUMS mice (P<0.05 or P<0.01). Furthermore, NKT repressed CUMS-induced activation of NF-κB signaling and NLRP3 inflammasome (P<0.01). More important, Nigericin, a NLRP3 activator, destroyed the effect of NKT on repressing neuroinflammation and improving depressive-like behaviors (P<0.05 or P<0.01).
CONCLUSION:NKT ameliorates the depressive-like symptoms, in part by repressing NF-κB/NLRP3-mediated neuroinflammation.
