1. Academic Validation
  2. Cynaroside improved depressive-like behavior in CUMS mice by suppressing microglial inflammation and ferroptosis

Cynaroside improved depressive-like behavior in CUMS mice by suppressing microglial inflammation and ferroptosis

  • Biomed Pharmacother. 2024 Mar 14:173:116425. doi: 10.1016/j.biopha.2024.116425.
Yiwei Zhou 1 Yuhan Huang 1 Wei Ye 2 Zijie Chen 3 Zhengzhong Yuan 4
Affiliations

Affiliations

  • 1 Department of Traditional Chinese Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
  • 2 School Of Chinese Medicine, Wenzhou Medical University, Wenzhou 325000, China.
  • 3 Beijing University of Chinese Medicine, Beijing 100029, China. Electronic address: chenzijie2002@163.com.
  • 4 Department of Traditional Chinese Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China. Electronic address: wzyzz2008@126.com.
Abstract

Depression is a common mental health disorder, and in recent years, the incidence of various forms of depression has been on the rise. Most medications for depression are highly dependency-inducing and can lead to relapse upon discontinuation. Therefore, novel treatment modalities and therapeutic targets are urgently required. Traditional Chinese medicine (TCM) offers advantages in the treatment of depression owing to its multi-target, multi-dimensional approach that addresses the root cause of depression by regulating organ functions and balancing Yin and Yang, with minimal side effects. Cynaroside (CNS), an extract from the traditional Chinese herb honeysuckle, is a flavonoid compound with antioxidant properties. In this study, network pharmacology identified 44 potential targets of CNS associated with depression and several highly correlated inflammatory signaling pathways. CNS alleviated LPS-induced M1 polarization and the release of inflammatory factors in BV-2 cells. Transcriptomic analysis and validation revealed that CNS reduced inflammatory polarization, lipid peroxidation, and Ferroptosis via the IRF1/SLC7A11/GPX4 signaling pathway. In vivo experiments showed that CNS treatment had effects similar to those of fluoxetine (FLX). It effectively ameliorated anxiety-, despair-, and anhedonia-like states in chronic unpredictable mild stress (CUMS)-induced mice and reduced microglial activation in the hippocampus. Thus, we conclude that CNS exerts its therapeutic effect on depression by inhibiting microglial cells from polarizing into the M1 phenotype and reducing inflammation and Ferroptosis levels. This study provides further evidence that CNS is a potential antidepressant, offering new avenues for the treatment of depression.

Keywords

CUMS; IRF1; M1 polarization; cynaroside; depression; ferroptosis.

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