An Zhou, Hao-Yinghua Feng, Chu-Ning Fan, Jun Wang, Zhong-Yu Yuan, Guang-Hui Xu, Cheng-Fu Li, Wei-Feng Huang, Li-Tao Yi
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引用次数: 0
Abstract
Purpose: Ferroptosis, characterized by iron-dependent lipid reactive oxygen species accumulation, plays a critical role in the pathophysiology of depression. Our research aims to elucidate the potential antidepressant mechanisms of asiaticoside, a bioactive compound known for its neuroprotective and immunomodulatory properties.
Methods: The antidepressant-like properties of asiaticoside in a model of chronic restraint stress (CRS)-induced depression in mice, with a particular focus on its interaction with ferroptosis-related pathways.
Results: The behavioral results revealed that asiaticoside significantly ameliorated CRS-induced depressive symptoms, as evidenced by increased sucrose preference and reduced immobility time. At the molecular level, asiaticoside enhanced the expression of brain-derived neurotrophic factor (BDNF), phosphorylated tropomyosin receptor kinase B (pTrkB), phosphorylated nuclear factor erythroid 2-related factor 2 (pNrf2), glutathione peroxidase 4 (GPX4), and solute carrier family 7 member 11 (SLC7A11), indicating its neuroprotective and antioxidative effects. In addition, asiaticoside suppressed the expression of ferroptosis markers, including ferritin light chain (FLC) and transferrin receptor only in CA1 region. Transmission electron microscopy (TEM) further confirmed that asiaticoside preserved mitochondrial integrity in CA1 neuronal cells.
Conclusion: In conclusion, our findings suggest that asiaticoside exerts its antidepressant-like effects through the modulation of BDNF/Nrf2/GPX4 signaling pathway against neuronal ferroptosis in the hippocampal CA1 region.
期刊介绍：
Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications.
The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas.
Specific topics covered by the journal include:
Drug target identification and validation
Phenotypic screening and target deconvolution
Biochemical analyses of drug targets and their pathways
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Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes)
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Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products**
Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development
Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing)
Preclinical development studies
Translational animal models
Mechanisms of action and signalling pathways
Toxicology
Gene therapy, cell therapy and immunotherapy
Personalized medicine and pharmacogenomics
Clinical drug evaluation
Patient safety and sustained use of medicines.
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