Cynaroside improved depressive-like behavior in CUMS mice by suppressing microglial inflammation and ferroptosis - 22/03/24
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.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | The prospective targets of Cynaroside in the context of depression was anticipated using network pharmacology analysis. |
• | Cynaroside was found to regulate LPS-induced BV-2 cells via ferroptosis and inflammatory responses by transcriptomics. |
• | Cynaroside ameliorated ferroptosis through activating the IRF1/SLC7A11/GPX4 signaling pathway. |
• | Cynaroside reversed depressive-like behaviors and attenuated pathological damage in the hippocampus of CUMS mice. |
Abbreviations : CCK8, CUMS, CNS, ELISA, EPM, FLX, FST, GPX4, GSH, H&E, Iba-1, INOS, IL-4, IL-6, IL-10, IRF1, MBT, OFT, QRT-PCR, SLC7A11, SPT, TST
Keywords : depression, CUMS, cynaroside, ferroptosis, M1 polarization, IRF1
Plan
Vol 173
Article 116425- avril 2024 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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