{"title":"Investigating the Mechanism of Astragalus mongholicus-Mediated Treatment of Silicosis in Mice from the Perspective of Alternative Splicing.","authors":"Yu Zhang, Zhiyan Jiang, Yuanyuan Zhai, Yongqiang Xing","doi":"10.2174/0113894501408966250903070801","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Astragalus mongholicus is distributed in Inner Mongolia, China, and has a certain therapeutic effect on silicosis. However, the regulatory mechanisms of Astragalus mongholicus mediated by alternative splicing (AS) in silicosis pathology and treatment remain unclear.</p><p><strong>Methods: </strong>The pathological examination was performed on the lung tissue of a constructed mouse model of silicosis. Then, rMATS-based AS detection, target prediction, PPI analysis, and molecular docking were conducted to investigate the mechanism of Astragalus mongholicus-mediated treatment of silicosis in mice from the perspective of AS.</p><p><strong>Results: </strong>A total of 404 differentially alternatively spliced genes (DASGs) were identified between the Astragalus mongholicus treatment and the silicosis model group. Moreover, 194 potential targets were predicted from 33 active components of Astragalus mongholicus, of which the targets, Rps6ka2 and Clk4, underwent differential AS. Network pharmacology analysis indicated that the Isomucronulatol, 7-o-methylisomucronulatol, and Medicarpin in Astragalus mongholicus might participate in the treatment of silicosis through differential spliced of Rps6ka2 or Clk4. Molecular docking confirmed a strong binding affinity between the protein Rps6ka2 and Medicarpin.</p><p><strong>Discussion: </strong>This study suggests that Isomucronulatol, 7-o-methylisomucronulatol, and Medicarpin, being active components in Astragalus mongholicus, may intervene in silicosis pathogenesis through differential splicing of Rps6ka2 or Clk4, involving biological processes such as protein serine/threonine kinase activity. However, further experimental validation is required to confirm these findings.</p><p><strong>Conclusion: </strong>A large number of DASEs exist in the development and treatment of silicosis. Astragalus mongholicus may alleviate silicosis through AS-regulated mechanisms involving Rps6ka2 and Clk4. This finding provides novel strategies and potential molecular targets for silicosis treatment.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":2.5000,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current drug targets","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0113894501408966250903070801","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction: Astragalus mongholicus is distributed in Inner Mongolia, China, and has a certain therapeutic effect on silicosis. However, the regulatory mechanisms of Astragalus mongholicus mediated by alternative splicing (AS) in silicosis pathology and treatment remain unclear.
Methods: The pathological examination was performed on the lung tissue of a constructed mouse model of silicosis. Then, rMATS-based AS detection, target prediction, PPI analysis, and molecular docking were conducted to investigate the mechanism of Astragalus mongholicus-mediated treatment of silicosis in mice from the perspective of AS.
Results: A total of 404 differentially alternatively spliced genes (DASGs) were identified between the Astragalus mongholicus treatment and the silicosis model group. Moreover, 194 potential targets were predicted from 33 active components of Astragalus mongholicus, of which the targets, Rps6ka2 and Clk4, underwent differential AS. Network pharmacology analysis indicated that the Isomucronulatol, 7-o-methylisomucronulatol, and Medicarpin in Astragalus mongholicus might participate in the treatment of silicosis through differential spliced of Rps6ka2 or Clk4. Molecular docking confirmed a strong binding affinity between the protein Rps6ka2 and Medicarpin.
Discussion: This study suggests that Isomucronulatol, 7-o-methylisomucronulatol, and Medicarpin, being active components in Astragalus mongholicus, may intervene in silicosis pathogenesis through differential splicing of Rps6ka2 or Clk4, involving biological processes such as protein serine/threonine kinase activity. However, further experimental validation is required to confirm these findings.
Conclusion: A large number of DASEs exist in the development and treatment of silicosis. Astragalus mongholicus may alleviate silicosis through AS-regulated mechanisms involving Rps6ka2 and Clk4. This finding provides novel strategies and potential molecular targets for silicosis treatment.
期刊介绍：
Current Drug Targets aims to cover the latest and most outstanding developments on the medicinal chemistry and pharmacology of molecular drug targets e.g. disease specific proteins, receptors, enzymes, genes.
Current Drug Targets publishes guest edited thematic issues written by leaders in the field covering a range of current topics of drug targets. The journal also accepts for publication mini- & full-length review articles and drug clinical trial studies.
As the discovery, identification, characterization and validation of novel human drug targets for drug discovery continues to grow; this journal is essential reading for all pharmaceutical scientists involved in drug discovery and development.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
