{"title":"别离胶囊抗肝纤维化的有效成分及分子机理:高分辨质谱分析、网络药理分析及实验验证","authors":"Kefeng Cao, Hui Jiang, Lili Zhang, Chang Fan, Zhigang Feng, Biao Li, Laicheng Song, Qun Zhang","doi":"10.2174/0113862073338867240930031800","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Biejiaruangan capsule (BJRGC) is a commonly used traditional Chinese medicine preparation for treating oftreating liver fibrosis (LF), but its specific molecular mechanism is unclear. This study used mass spectrometry, network pharmacology and experimental verification to explore the mechanism of BJRGC against LF.</p><p><strong>Methods: </strong>Ultrahigh-performance liquid chromatography-quadrupole-exactive-orbitrap-mass spectrometry (UHPLC-Q-Exactive-Orbitrap-MS) and network pharmacology were employed to identify and screen the potential components, targets, and signaling pathways of BJRGC against LF. The interaction between the active ingredients and targets was validated using molecular docking. Finally, 5-ethynyl-2'-deoxyuridine (EDU) staining, western blotting (WB), and flow cytometry (FCM) were utilized to further verify the mechanism of BJRGC against LF.</p><p><strong>Results: </strong>A total of 9 prototype components of BJRGC were identified in serum, most derived from iridoid glycosides and triterpenes in Gardenia jasminoides Ellis and Artemisia scoparia Waldst.et Kit. Network pharmacology predicts that medicine prototype components in serum mostly influence targets such as CDK2, CDK6, and PIK3CG, with the key route being the PI3K/AKT signaling pathway. Molecular docking showed that the major components have good binding properties with key target proteins. The experimental results showed that BJRGC could inhibit the proliferation of HSCs, induce cell cycle arrest and reduce the protein expression of CDK2, CDK6 and PIK3CG.</p><p><strong>Conclusions: </strong>BJRGC can inhibit the proliferation of HSCs by targeting the protein expression of CDK2, CDK6, and PIK3CG in the PI3K/AKT signaling pathway through its prototype components, such as hyperoside, tumulosic acid, and hederagenin, thereby alleviating LF disease.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6000,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Effective Components and Molecular Mechanism of Biejiaruangan Capsule Against Liver Fibrosis: High-resolution Mass Spectrometry, Network Pharmacological Analysis and Experimental Verification.\",\"authors\":\"Kefeng Cao, Hui Jiang, Lili Zhang, Chang Fan, Zhigang Feng, Biao Li, Laicheng Song, Qun Zhang\",\"doi\":\"10.2174/0113862073338867240930031800\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Biejiaruangan capsule (BJRGC) is a commonly used traditional Chinese medicine preparation for treating oftreating liver fibrosis (LF), but its specific molecular mechanism is unclear. This study used mass spectrometry, network pharmacology and experimental verification to explore the mechanism of BJRGC against LF.</p><p><strong>Methods: </strong>Ultrahigh-performance liquid chromatography-quadrupole-exactive-orbitrap-mass spectrometry (UHPLC-Q-Exactive-Orbitrap-MS) and network pharmacology were employed to identify and screen the potential components, targets, and signaling pathways of BJRGC against LF. The interaction between the active ingredients and targets was validated using molecular docking. Finally, 5-ethynyl-2'-deoxyuridine (EDU) staining, western blotting (WB), and flow cytometry (FCM) were utilized to further verify the mechanism of BJRGC against LF.</p><p><strong>Results: </strong>A total of 9 prototype components of BJRGC were identified in serum, most derived from iridoid glycosides and triterpenes in Gardenia jasminoides Ellis and Artemisia scoparia Waldst.et Kit. Network pharmacology predicts that medicine prototype components in serum mostly influence targets such as CDK2, CDK6, and PIK3CG, with the key route being the PI3K/AKT signaling pathway. Molecular docking showed that the major components have good binding properties with key target proteins. The experimental results showed that BJRGC could inhibit the proliferation of HSCs, induce cell cycle arrest and reduce the protein expression of CDK2, CDK6 and PIK3CG.</p><p><strong>Conclusions: </strong>BJRGC can inhibit the proliferation of HSCs by targeting the protein expression of CDK2, CDK6, and PIK3CG in the PI3K/AKT signaling pathway through its prototype components, such as hyperoside, tumulosic acid, and hederagenin, thereby alleviating LF disease.</p>\",\"PeriodicalId\":10491,\"journal\":{\"name\":\"Combinatorial chemistry & high throughput screening\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":1.6000,\"publicationDate\":\"2024-10-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Combinatorial chemistry & high throughput screening\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2174/0113862073338867240930031800\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"BIOCHEMICAL RESEARCH METHODS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Combinatorial chemistry & high throughput screening","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0113862073338867240930031800","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
Effective Components and Molecular Mechanism of Biejiaruangan Capsule Against Liver Fibrosis: High-resolution Mass Spectrometry, Network Pharmacological Analysis and Experimental Verification.
Background: Biejiaruangan capsule (BJRGC) is a commonly used traditional Chinese medicine preparation for treating oftreating liver fibrosis (LF), but its specific molecular mechanism is unclear. This study used mass spectrometry, network pharmacology and experimental verification to explore the mechanism of BJRGC against LF.
Methods: Ultrahigh-performance liquid chromatography-quadrupole-exactive-orbitrap-mass spectrometry (UHPLC-Q-Exactive-Orbitrap-MS) and network pharmacology were employed to identify and screen the potential components, targets, and signaling pathways of BJRGC against LF. The interaction between the active ingredients and targets was validated using molecular docking. Finally, 5-ethynyl-2'-deoxyuridine (EDU) staining, western blotting (WB), and flow cytometry (FCM) were utilized to further verify the mechanism of BJRGC against LF.
Results: A total of 9 prototype components of BJRGC were identified in serum, most derived from iridoid glycosides and triterpenes in Gardenia jasminoides Ellis and Artemisia scoparia Waldst.et Kit. Network pharmacology predicts that medicine prototype components in serum mostly influence targets such as CDK2, CDK6, and PIK3CG, with the key route being the PI3K/AKT signaling pathway. Molecular docking showed that the major components have good binding properties with key target proteins. The experimental results showed that BJRGC could inhibit the proliferation of HSCs, induce cell cycle arrest and reduce the protein expression of CDK2, CDK6 and PIK3CG.
Conclusions: BJRGC can inhibit the proliferation of HSCs by targeting the protein expression of CDK2, CDK6, and PIK3CG in the PI3K/AKT signaling pathway through its prototype components, such as hyperoside, tumulosic acid, and hederagenin, thereby alleviating LF disease.
期刊介绍:
Combinatorial Chemistry & High Throughput Screening (CCHTS) publishes full length original research articles and reviews/mini-reviews dealing with various topics related to chemical biology (High Throughput Screening, Combinatorial Chemistry, Chemoinformatics, Laboratory Automation and Compound management) in advancing drug discovery research. Original research articles and reviews in the following areas are of special interest to the readers of this journal:
Target identification and validation
Assay design, development, miniaturization and comparison
High throughput/high content/in silico screening and associated technologies
Label-free detection technologies and applications
Stem cell technologies
Biomarkers
ADMET/PK/PD methodologies and screening
Probe discovery and development, hit to lead optimization
Combinatorial chemistry (e.g. small molecules, peptide, nucleic acid or phage display libraries)
Chemical library design and chemical diversity
Chemo/bio-informatics, data mining
Compound management
Pharmacognosy
Natural Products Research (Chemistry, Biology and Pharmacology of Natural Products)
Natural Product Analytical Studies
Bipharmaceutical studies of Natural products
Drug repurposing
Data management and statistical analysis
Laboratory automation, robotics, microfluidics, signal detection technologies
Current & Future Institutional Research Profile
Technology transfer, legal and licensing issues
Patents.