2. Academic Validation
  3. Magnolol attenuates depressive-like behaviors by polarizing microglia towards the M2 phenotype through the regulation of Nrf2/HO-1/NLRP3 signaling pathway

Magnolol attenuates depressive-like behaviors by polarizing microglia towards the M2 phenotype through the regulation of Nrf2/HO-1/NLRP3 signaling pathway

  • Phytomedicine. 2021 Oct:91:153692. doi: 10.1016/j.phymed.2021.153692.
Weiwei Tao 1,  Yuwen Hu 2,  Zhaoyang Chen 3,  Yuxin Dai 3,  Yue Hu 4,  Mingming Qi 5
Affiliations

Affiliations

  • 1 School of Chinese Medicine, School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 220023, China.
  • 2 Jiangsu Medical Device Testing Institute, Nanjing 220023, China.
  • 3 School of Chinese Medicine, School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • 4 School of Chinese Medicine, School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: 290510@njucm.edu.cn.
  • 5 School of Chinese Medicine, School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: qmm@njucm.edu.cn.
PMID: 34411834 DOI: 10.1016/j.phymed.2021.153692
Abstract

Purpose: Magnolol (MA) exhibits anti-depressant effect by inhibiting inflammation. However, its effect on microglia polarization remains not fully understood. Herein, our study was performed to evaluate the effect of MA on microglia polarization in chronic unpredictable mild stress (CUMS)-induced depression and explore its potential mechanism.

Study design: The CUMS procedure was conducted, and the mice were intragastrically treated with MA. BV2 cells were pretreated with MA prior to LPS/ATP challenge.

Methods: The levels of TNF-α, IL-1β, IL-6 and IL-4, IL-10 in brain and BV2 cells were examined by ELISA. The mRNA expressions of Arg1, Ym1, Fizz1 and Klf4 in brains were measured. ROS content was determined using flow cytometry. Immunofluorescence was employed to evaluate Iba-1 level, Nrf2 nuclear translocation, Iba-1+CD16/32+ and Iba-1+CD206+ cell population. The protein expressions of Nrf2, HO-1, NLRP3, Caspase-1 p20 and IL-1β in brains and BV2 cells were investigated by western blot. Nrf2 siRNA was induced in experiments to explore the role of Nrf2 in MA-mediated microglia polarization. The ubiquitination of Nrf2 was visualized by Co-IP.

Results: The treatment with MA notably relieved depressive like behaviors, suppressed pro-inflammatory cytokines, promoted anti-inflammatory cytokines and the transcription of M2 phenotype microglia-specific Indicators. MA upregulated the expression of Nrf2, HO-1, downregulated the expression of NLRP3, Caspase-1 p20, IL-1β both in vivo and in vitro. MA also reduced ROS concentration, promoted Nrf2 nucleus translocation and prevented Nrf2 ubiquitination. Nrf2 Knockdown by siRNA abolished the MA-mediated microglia polarization.

Conclusion: The present research demonstrated that MA attenuated CUMS-stimulated depression by inhibiting M1 polarization and inducing M2 polarization via Nrf2/HO-1/NLRP3 signaling.

Keywords

CUMS; Depression; Magnolol; Microglia polarization; Nrf2/HO-1/NLRP3 signaling.

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