{"title":"西诺明通过抑制 PI3K-Akt 信号通路缓解类风湿性关节炎，网络药理学、分子对接和实验验证证明了这一点","authors":"Qingyang Liu, Jian Wang, Chunhui Ding, Ying Chu, Fengying Jiang, Yunxia Hu, Haifeng Li, Qiubo Wang","doi":"10.2147/dddt.s475959","DOIUrl":null,"url":null,"abstract":"<strong>Purpose:</strong> Sinomenine (SIN) is commonly used in Traditional Chinese Medicine (TCM) as a respected remedy for rheumatoid arthritis (RA). Nevertheless, the therapeutic mechanism of SIN in RA remains incompletely understood. This study aimed to delve into the molecular mechanism of SIN in the treatment of RA.<br/><strong>Methods:</strong> The potential targets of SIN were predicted using the TCMSP server, STITCH database, and SwissTarget Prediction. Differentially expressed genes (DEGs) in RA were obtained from the GEO database. Enrichment analyses and molecular docking were conducted to explore the potential mechanism of SIN in the treatment of RA. In vitro and in vivo studies were conducted to validate the intervention effects of SIN on rheumatoid arthritis, as determined through network pharmacology analyses.<br/><strong>Results:</strong> A total of 39 potential targets associated with the therapeutic effects of SIN in RA were identified. Enrichment analysis revealed that these potential targets are primarily enriched in PI3K-Akt signaling pathway, and the molecular docking suggests that SIN may act on specific proteins in the pathway. Experimental results have shown that exposure to SIN inhibits cytokine secretion, promotes apoptosis, reduces metastasis and invasion, and blocks the activation of the PI3K-Akt signaling pathway in RA fibroblast-like synoviocytes (RA-FLS). Moreover, SIN treatment alleviated arthritis-related symptoms and regulated the differentiation of CD4+ T cells in the spleen of collagen-induced arthritis (CIA) mice.<br/><strong>Conclusion:</strong> By utilizing network pharmacology, molecular modeling, and in vitro/in vivo validation, this study demonstrates that SIN can alleviate RA by inhibiting the PI3K-Akt signaling pathway. These findings enhance the understanding of the therapeutic mechanisms of SIN in RA, offering a stronger theoretical foundation for its future clinical application. <br/><br/><strong>Keywords:</strong> sinomenine, rheumatoid arthritis, network pharmacology, PI3K-Akt signaling pathway<br/>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":null,"pages":null},"PeriodicalIF":4.7000,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Sinomenine Alleviates Rheumatoid Arthritis by Suppressing the PI3K-Akt Signaling Pathway, as Demonstrated Through Network Pharmacology, Molecular Docking, and Experimental Validation\",\"authors\":\"Qingyang Liu, Jian Wang, Chunhui Ding, Ying Chu, Fengying Jiang, Yunxia Hu, Haifeng Li, Qiubo Wang\",\"doi\":\"10.2147/dddt.s475959\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<strong>Purpose:</strong> Sinomenine (SIN) is commonly used in Traditional Chinese Medicine (TCM) as a respected remedy for rheumatoid arthritis (RA). Nevertheless, the therapeutic mechanism of SIN in RA remains incompletely understood. This study aimed to delve into the molecular mechanism of SIN in the treatment of RA.<br/><strong>Methods:</strong> The potential targets of SIN were predicted using the TCMSP server, STITCH database, and SwissTarget Prediction. Differentially expressed genes (DEGs) in RA were obtained from the GEO database. Enrichment analyses and molecular docking were conducted to explore the potential mechanism of SIN in the treatment of RA. In vitro and in vivo studies were conducted to validate the intervention effects of SIN on rheumatoid arthritis, as determined through network pharmacology analyses.<br/><strong>Results:</strong> A total of 39 potential targets associated with the therapeutic effects of SIN in RA were identified. Enrichment analysis revealed that these potential targets are primarily enriched in PI3K-Akt signaling pathway, and the molecular docking suggests that SIN may act on specific proteins in the pathway. Experimental results have shown that exposure to SIN inhibits cytokine secretion, promotes apoptosis, reduces metastasis and invasion, and blocks the activation of the PI3K-Akt signaling pathway in RA fibroblast-like synoviocytes (RA-FLS). Moreover, SIN treatment alleviated arthritis-related symptoms and regulated the differentiation of CD4+ T cells in the spleen of collagen-induced arthritis (CIA) mice.<br/><strong>Conclusion:</strong> By utilizing network pharmacology, molecular modeling, and in vitro/in vivo validation, this study demonstrates that SIN can alleviate RA by inhibiting the PI3K-Akt signaling pathway. These findings enhance the understanding of the therapeutic mechanisms of SIN in RA, offering a stronger theoretical foundation for its future clinical application. <br/><br/><strong>Keywords:</strong> sinomenine, rheumatoid arthritis, network pharmacology, PI3K-Akt signaling pathway<br/>\",\"PeriodicalId\":11290,\"journal\":{\"name\":\"Drug Design, Development and Therapy\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.7000,\"publicationDate\":\"2024-08-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Drug Design, Development and Therapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2147/dddt.s475959\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug Design, Development and Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/dddt.s475959","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
摘要
目的：西诺明（SIN）是中医常用的治疗类风湿性关节炎（RA）的药物。然而，SIN 对 RA 的治疗机制仍不完全清楚。本研究旨在探讨 SIN 治疗 RA 的分子机制：方法：使用 TCMSP 服务器、STITCH 数据库和 SwissTarget Prediction 预测 SIN 的潜在靶点。方法：利用 TCMSP 服务器、STITCH 数据库和 SwissTarget Prediction 预测 SIN 的潜在靶点。进行了富集分析和分子对接，以探索 SIN 治疗 RA 的潜在机制。通过网络药理学分析，进行了体外和体内研究，以验证 SIN 对类风湿性关节炎的干预效果：结果：共发现了 39 个与 SIN 对类风湿关节炎的治疗效果相关的潜在靶点。富集分析表明，这些潜在靶点主要富集在PI3K-Akt信号通路中，分子对接表明SIN可能作用于该通路中的特定蛋白。实验结果表明，暴露于SIN可抑制细胞因子分泌、促进细胞凋亡、减少转移和侵袭，并阻断PI3K-Akt信号通路在RA成纤维细胞样滑膜细胞（RA-FLS）中的激活。此外，SIN治疗可减轻关节炎相关症状，并调节胶原诱导的关节炎（CIA）小鼠脾脏中CD4+ T细胞的分化：通过利用网络药理学、分子建模和体外/体内验证，本研究证明了SIN可以通过抑制PI3K-Akt信号通路来缓解RA。这些发现加深了人们对SIN在RA中治疗机制的理解，为其未来的临床应用提供了更坚实的理论基础。关键词：西诺明；类风湿性关节炎；网络药理学；PI3K-Akt 信号通路
Sinomenine Alleviates Rheumatoid Arthritis by Suppressing the PI3K-Akt Signaling Pathway, as Demonstrated Through Network Pharmacology, Molecular Docking, and Experimental Validation
Purpose: Sinomenine (SIN) is commonly used in Traditional Chinese Medicine (TCM) as a respected remedy for rheumatoid arthritis (RA). Nevertheless, the therapeutic mechanism of SIN in RA remains incompletely understood. This study aimed to delve into the molecular mechanism of SIN in the treatment of RA. Methods: The potential targets of SIN were predicted using the TCMSP server, STITCH database, and SwissTarget Prediction. Differentially expressed genes (DEGs) in RA were obtained from the GEO database. Enrichment analyses and molecular docking were conducted to explore the potential mechanism of SIN in the treatment of RA. In vitro and in vivo studies were conducted to validate the intervention effects of SIN on rheumatoid arthritis, as determined through network pharmacology analyses. Results: A total of 39 potential targets associated with the therapeutic effects of SIN in RA were identified. Enrichment analysis revealed that these potential targets are primarily enriched in PI3K-Akt signaling pathway, and the molecular docking suggests that SIN may act on specific proteins in the pathway. Experimental results have shown that exposure to SIN inhibits cytokine secretion, promotes apoptosis, reduces metastasis and invasion, and blocks the activation of the PI3K-Akt signaling pathway in RA fibroblast-like synoviocytes (RA-FLS). Moreover, SIN treatment alleviated arthritis-related symptoms and regulated the differentiation of CD4+ T cells in the spleen of collagen-induced arthritis (CIA) mice. Conclusion: By utilizing network pharmacology, molecular modeling, and in vitro/in vivo validation, this study demonstrates that SIN can alleviate RA by inhibiting the PI3K-Akt signaling pathway. These findings enhance the understanding of the therapeutic mechanisms of SIN in RA, offering a stronger theoretical foundation for its future clinical application.
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
New methods or relevant applications in molecular/drug design and computer-aided drug discovery*
Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes)
Structural or molecular biological studies elucidating molecular recognition processes
Fragment-based drug discovery
Pharmaceutical/red biotechnology
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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