Elucidating the Mechanism of Emodin in Treating Post-Stroke Depression Through Network Pharmacology and Animal Experiments

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics Pub Date : 2025-09-24 DOI:10.1111/cns.70581

Xiaoju Liu, Jie Gao, Kai Yang, Weiming Zhu, Ming Su, Zichun Liu, Yaxin Yuan, Linya Cao, Tong Wu, Wei Liu

{"title":"Elucidating the Mechanism of Emodin in Treating Post-Stroke Depression Through Network Pharmacology and Animal Experiments","authors":"Xiaoju Liu, Jie Gao, Kai Yang, Weiming Zhu, Ming Su, Zichun Liu, Yaxin Yuan, Linya Cao, Tong Wu, Wei Liu","doi":"10.1111/cns.70581","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Objective</h3>\n \n <p>Evaluate the mechanism of Emodin therapy for Post-stroke depression (PSD) using network pharmacology and animal experiments.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Firstly, the effectiveness of Em in treating PSD was confirmed by constructing a PSD rat model. Then, network pharmacology and molecular docking techniques were used to analyze the potential signaling pathways and targets of Em therapy for PSD. Further exploration and validation were conducted using the PSD rat model. Finally, the expressions of tissue plasminogen activator (tPA), matrix metallopeptidase-9 (MMP9), furin, and proprotein convertases (PC) in the hippocampus and medial prefrontal cortex (mPFC) were further detected.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Em exhibited significant neuroprotective and antidepressant effects on PSD. Network pharmacology analysis revealed that Em may exert pharmacological effects on PSD through 47 core targets. These targets were involved in multiple signaling pathways. Molecular docking studies demonstrated that Em had a strong binding affinity for core targets. Animal experiments further indicated that Em could regulate the expression of precursor brain-derived neurotrophic factor (proBDNF) and mature BDNF (mBDNF) in the hippocampus and mPFC, ameliorating apoptosis. In addition, Em could upregulate the expression of tPA gene and protein in the hippocampus and mPFC, as well as upregulate the expression of Furin gene and protein in the mPFC. This confirmed that the balance regulation of proBDNF/mBDNF depends on tPA and Furin.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>The therapeutic effects of Em on PSD are multi-targets and multi-pathways. Em may exert therapeutic effects on PSD by binding to the core target, BDNF. The mechanism may be to regulate the balance proBDNF/mBDNF via tPA and Furin, improving apoptosis.</p>\n </section>\n </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0000,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70581","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"CNS Neuroscience & Therapeutics","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/cns.70581","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}

引用次数: 0

Abstract

Objective

Evaluate the mechanism of Emodin therapy for Post-stroke depression (PSD) using network pharmacology and animal experiments.

Methods

Firstly, the effectiveness of Em in treating PSD was confirmed by constructing a PSD rat model. Then, network pharmacology and molecular docking techniques were used to analyze the potential signaling pathways and targets of Em therapy for PSD. Further exploration and validation were conducted using the PSD rat model. Finally, the expressions of tissue plasminogen activator (tPA), matrix metallopeptidase-9 (MMP9), furin, and proprotein convertases (PC) in the hippocampus and medial prefrontal cortex (mPFC) were further detected.

Results

Em exhibited significant neuroprotective and antidepressant effects on PSD. Network pharmacology analysis revealed that Em may exert pharmacological effects on PSD through 47 core targets. These targets were involved in multiple signaling pathways. Molecular docking studies demonstrated that Em had a strong binding affinity for core targets. Animal experiments further indicated that Em could regulate the expression of precursor brain-derived neurotrophic factor (proBDNF) and mature BDNF (mBDNF) in the hippocampus and mPFC, ameliorating apoptosis. In addition, Em could upregulate the expression of tPA gene and protein in the hippocampus and mPFC, as well as upregulate the expression of Furin gene and protein in the mPFC. This confirmed that the balance regulation of proBDNF/mBDNF depends on tPA and Furin.

Conclusion

The therapeutic effects of Em on PSD are multi-targets and multi-pathways. Em may exert therapeutic effects on PSD by binding to the core target, BDNF. The mechanism may be to regulate the balance proBDNF/mBDNF via tPA and Furin, improving apoptosis.

Abstract Image

查看原文本刊更多论文

网络药理及动物实验探讨大黄素治疗脑卒中后抑郁的机制。

目的：通过网络药理学和动物实验探讨大黄素治疗脑卒中后抑郁的作用机制。方法：首先，通过构建PSD大鼠模型，验证Em对PSD的治疗作用。然后，利用网络药理学和分子对接技术分析Em治疗PSD的潜在信号通路和靶点。采用PSD大鼠模型进行进一步的探索和验证。最后，进一步检测海马和内侧前额叶皮层（mPFC）组织纤溶酶原激活物（tPA）、基质金属肽酶-9 （MMP9）、furin和蛋白转化酶（PC）的表达。结果：Em对PSD有明显的神经保护作用和抗抑郁作用。网络药理学分析显示，Em可能通过47个核心靶点对PSD产生药理作用。这些靶标参与了多种信号通路。分子对接研究表明，Em对核心靶点具有较强的结合亲和力。动物实验进一步表明，Em可调节海马和mPFC中前体脑源性神经营养因子（proBDNF）和成熟脑源性神经营养因子（mBDNF）的表达，改善凋亡。此外，Em可上调海马和mPFC中tPA基因和蛋白的表达，上调mPFC中Furin基因和蛋白的表达。这证实了proBDNF/mBDNF的平衡调节依赖于tPA和Furin。结论：Em对PSD的治疗作用是多靶点、多途径的。Em可能通过结合核心靶点BDNF对PSD产生治疗作用。其机制可能是通过tPA和Furin调节proBDNF/mBDNF的平衡，促进细胞凋亡。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

CNS Neuroscience & Therapeutics 医学-神经科学

CiteScore

7.30

自引率

12.70%

发文量

240

审稿时长

2 months

期刊介绍： CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.