ArticleNeuropsychiatric disease and treatment2021
Traditional Chinese Formula Xiaoyaosan Alleviates Depressive-Like Behavior in CUMS Mice by Regulating PEBP1-GPX4-Mediated Ferroptosis in the Hippocampus.
Article in Neuropsychiatric disease and treatment, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 3 of them syntheses that pooled it.
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Who cites it
52 citing papers in PubMed, 3 syntheses or guidelines pooled it, 89 citations in OpenAlex.
- Efficacy and Potential Mechanism of Chinese Herbal Formula Chaihu Shugan Powder on Animal Models of Depression: A Systematic Review and Meta-Analysis.CNS neuroscience & therapeutics · 2025Pooled it
- Effects of modified Soyo-san (Xiao-yao-san, Shoyo-san) combined with antidepressants on post-stroke depression and functional recovery: a systematic review and meta-analysis.Frontiers in pharmacology · 2025Pooled it
- The antidepressive mechanism of Longya Lilium combined with Fluoxetine in mice with depression-like behaviors.NPJ systems biology and applications · 2024Pooled it
- Ferroptosis in major depressive disorder: Molecular mechanisms, cellular vulnerability, and therapeutic opportunities.Biochemistry and biophysics reports · 2026Review
- Ferroptosis in depression: mechanisms, association, and therapeutic strategies.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- ACSL4 in Alzheimer's disease: Pathogenetic mechanisms and potential therapeutic targets.Genes & diseases · 2026Review
- Anti-HMGB1 Antibody Therapy Ameliorates Depression Following Spinal Cord Injury in Rats by Inhibiting Ferroptosis.Journal of cellular and molecular medicine · 2026Article
- Ferroptosis in Neuropsychiatric and Neurodegenerative Disorders: Shared Mechanisms and Disease-Specific Signatures.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Targeting ferroptosis as a novel strategy for depressive mental disorders.Psychopharmacology · 2026Review
- Dietary advanced glycation products combined with chronic restraint stress induced anxiety-like and depression-like behaviors in male mice.NPJ science of food · 2026Article
- Astrocytic PCBP1 Suppresses Ferroptosis to Restore Glutamatergic Homeostasis and Mitigate Stress-Induced Depression in Male Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeting Programmed Cell Death in Depression: A Review of Traditional Chinese Medicine Interventions Based on Preclinical Evidence.Neuropsychiatric disease and treatment · 2026Review
- Resveratrol alleviates depressive-like behavior via the activation of SIRT1/NF-κB signaling pathway in microglia.Future science OA · 2025Article
- Analysis of the Correlation Between Depression-like Behaviors and Lipid Peroxidation in the Prefrontal Cortex of Mice: The Impact of Early Life Stress.Brain sciences · 2025Article
- Butyric acid and valeric acid attenuate stress-induced ferroptosis and depressive-like behaviors by suppressing hippocampal neuroinflammation.Journal of translational medicine · 2025Article
- Ferroptosis: a new target for depression prevention and treatment.Journal of neural transmission (Vienna, Austria : 1996) · 2025Review
- The Ferroptosis-Mitochondrial Axis in Depression: Unraveling the Feedforward Loop of Oxidative Stress, Metabolic Homeostasis Dysregulation, and Neuroinflammation.Antioxidants (Basel, Switzerland) · 2025Review
- Xiao Yao San mitigates corticosterone stimulation-induced hippocampal neuronal damage by inhibiting GR phosphorylation and nuclear translocation via FKBP4 involvement.BMC complementary medicine and therapies · 2025Article
- Yi-Nao-Jie-Yu Prescription Relieves Post-Stroke Depression by Mitigating Ferroptosis in Hippocampal Neurons Via Activating the Nrf2/GPX4/SLC7A11 Pathway.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- Activation of SIRT1 by Hydroxysafflor Yellow A Attenuates Chronic Unpredictable Mild Stress-Induced Microglia Activation and Iron Death in Depressed Rats.Brain and behavior · 2025Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAt present, the pathogenesis of depression is not fully understood, and nearly half of depression patients experience no obvious effects during treatment. This study aimed to establish a depression mouse model to explore the possible role of ferroptosis in the pathogenesis of depression, and observe the effects of Xiaoyaosan on PEBP1-GPX4-mediated ferroptosis in the hippocampus.
methodsForty-eight male C57BL/6 mice were randomly divided into a control group, CUMS group, Xiaoyaosan group and fluoxetine group, and the model was established by chronic unpredictable mild stress (CUMS) for a successive 6 weeks. The medication procedure was performed from the 4th to the 6th week of modeling. The behavioral evaluations were measured to evaluate depressive-like behaviors. The expressions of GPX4, FTH1, ACSL4 and COX2 were detected as ferroptosis-related indicators. Then, the total iron and ferrous content in the hippocampus were measured. The levels of PEBP1 and ERK1/2 were observed, and the expressions of GFAP and IBA1 were also detected to measure the functions of astrocytes and microglia in the hippocampus.
resultsEight herbs of Xiaoyaosan had 133 active ingredients which could regulate the 43 ferroptosis-related genes in depression. After 6 weeks of modeling, the data showed that mice in the CUMS group had obvious depressive-like behaviors, and medication with Xiaoyaosan or fluoxetine could significantly improve the behavioral changes. The expressions of GPX4, FTH1, ACSL4, COX2, PEBP1, ERK1/2, GFAP and IBA1 changed in the CUMS group mice, while the total iron and ferrous content also changed. Xiaoyaosan and fluoxetine had obvious curative effects that could significantly alleviate the above changes in the hippocampus.
conclusionOur results revealed that the activation of ferroptosis might exist in the hippocampi of CUMS-induced mice. The PEBP1-GPX4-mediated ferroptosis could be involved in the antidepressant mechanism of Xiaoyaosan. It also implied that ferroptosis could become a new target for research into the depression mechanism and antidepressant drugs.
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