Nootkatone Improves Chronic Unpredictable Mild Stress-Induced Depressive-Like Behaviors by Repressing NF-κB/NLRP3-Mediated Neuroin flammation

ZHAO Xin-hua; AN Na; XIA Meng-huan; LIU Wen-ping; WANG Qing-qi; BAO Ji-zhang

doi:10.1007/s11655-022-3725-2

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Nootkatone Improves Chronic Unpredictable Mild Stress-Induced Depressive-Like Behaviors by Repressing NF-κB/NLRP3-Mediated Neuroin flammation

Original Article | Updated：2023-01-05

- Nootkatone Improves Chronic Unpredictable Mild Stress-Induced Depressive-Like Behaviors by Repressing NF-κB/NLRP3-Mediated Neuroin flammation
- Nootkatone Improves Chronic Unpredictable Mild Stress-Induced Depressive-Like Behaviors by Repressing NF-κB/NLRP3-Mediated Neuroin flammation
- 中国结合医学杂志（英文版） 2023年29卷第1期页码：37-43
- Affiliations：
  
  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
- Author bio：
  
  Prof. BAO Ji-zhang, E-mail: baojizhang@shutcm.edu.cn
- Funds：
  
  the Future Plan of Shanghai Municipal Hospital of Traditional Chinese Medicine (2021) Inheritance Talent Project(WLJH2021ZY-MZY033);The Xinglin Inherit-patterned Talents Program of Shanghai University of Traditional Chinese Medicine,Shanghai University of Traditional Chinese Medicine (No. 10 (2019) of the Personnel Office of Shanghai University of TCM)
- DOI：10.1007/s11655-022-3725-2
  中图分类号：
- 纸质出版日期：2023-01-01，
  
  网络出版日期：2022-11-19，
  
  录用日期：2021-11-22
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Nootkatone Improves Chronic Unpredictable Mild Stress-Induced Depressive-Like Behaviors by Repressing NF-κB/NLRP3-Mediated Neuroin flammation[J]. 中国结合医学杂志（英文版）, 2023,29(1):37-43.

ZHAO Xin-hua, AN Na, XIA Meng-huan, et al. Nootkatone Improves Chronic Unpredictable Mild Stress-Induced Depressive-Like Behaviors by Repressing NF-κB/NLRP3-Mediated Neuroin flammation[J]. Chinese Journal of Integrative Medicine, 2023,29(1):37-43.
Nootkatone Improves Chronic Unpredictable Mild Stress-Induced Depressive-Like Behaviors by Repressing NF-κB/NLRP3-Mediated Neuroin flammation[J]. 中国结合医学杂志（英文版）, 2023,29(1):37-43. DOI： 10.1007/s11655-022-3725-2.

ZHAO Xin-hua, AN Na, XIA Meng-huan, et al. Nootkatone Improves Chronic Unpredictable Mild Stress-Induced Depressive-Like Behaviors by Repressing NF-κB/NLRP3-Mediated Neuroin flammation[J]. Chinese Journal of Integrative Medicine, 2023,29(1):37-43. DOI： 10.1007/s11655-022-3725-2.

摘要

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 depressivelike behaviors.

Methods:

The CUMS-induced depression model was established in mice. Fifty mice were randomized into 5 groups (

=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 depressivelike behaviors in mice (

0.05 or

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 (

0.05 or

0.01). Furthermore

NKT repressed CUMS-induced activation of NF-kB signaling and NLRP3 inflammasome (

0.01). More important

Nigericin

a NLRP3 activator

destroyed the effect of NKT on repressing neuroinflammation and improving depressive-like behaviors (

0.05 or

0.01).

Conclusion:

NKT ameliorates the depressive-like symptoms

in part by repressing NF-κB/NLRP3-mediated neuroinflammation.

关键词

Keywords

nootkatonedepressive disordernuclear factor-κBNOD-like receptor 3nuroinflammation

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