Rong Su, Yue Wang, Nixia Tan, Honglun Wang, Qi Dong
{"title":"唐古山莨菪中COX-2抑制剂的鉴定及分子机制:配体捕捞、体外验证、分子对接、分子动力学和ADMET分析","authors":"Rong Su, Yue Wang, Nixia Tan, Honglun Wang, Qi Dong","doi":"10.1002/bmc.70092","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p><i>Anisodus tanguticus</i> (Maxim.) Pascher has demonstrated remarkable inhibitory effects on cyclooxygenase-2 (COX-2); however, the effective substances and molecular mechanism remain ambiguous. In this study, surface plasmon resonance (SPR) ligand fishing technology coupled with UPLC-Q-TOF-MS analysis were applied to identify two COX-2 binders, atropine and fabiatrin, from <i>A. tanguticus</i> extracts. In vitro assays verified their potent COX-2 inhibitory effects, with IC<sub>50</sub> values of 16.63 and 10.66 mM, respectively. To elucidate the molecular mechanism underlying their inhibitory effects, we conducted molecular docking and molecular dynamics simulations. Interaction analysis revealed that both atropine and fabiatrin exhibit strong binding affinity and structural stability with COX-2. Subsequent ADMET (absorption, distribution, metabolism, excretion, and toxicity) predictions indicated that atropine and fabiatrin had favorable pharmacokinetic properties and low toxicity, suggesting their potential as anti-inflammatory agents. Notably, this is the first study to demonstrate the inhibitory effect of fabiatrin on COX-2. Overall, the integrated approach developed here provides an efficient and reliable strategy for identifying bioactive components from complex traditional Chinese medicine (TCM) systems, which may offer a new perspective and scientific basis for the research and development of naturally targeted drugs.</p>\n </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 6","pages":""},"PeriodicalIF":1.8000,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Identification and Molecular Mechanism of COX-2 Inhibitors From Anisodus tanguticus: Ligand Fishing, In Vitro Validation, Molecular Docking, Molecular Dynamics, and ADMET Analysis\",\"authors\":\"Rong Su, Yue Wang, Nixia Tan, Honglun Wang, Qi Dong\",\"doi\":\"10.1002/bmc.70092\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <p><i>Anisodus tanguticus</i> (Maxim.) Pascher has demonstrated remarkable inhibitory effects on cyclooxygenase-2 (COX-2); however, the effective substances and molecular mechanism remain ambiguous. In this study, surface plasmon resonance (SPR) ligand fishing technology coupled with UPLC-Q-TOF-MS analysis were applied to identify two COX-2 binders, atropine and fabiatrin, from <i>A. tanguticus</i> extracts. In vitro assays verified their potent COX-2 inhibitory effects, with IC<sub>50</sub> values of 16.63 and 10.66 mM, respectively. To elucidate the molecular mechanism underlying their inhibitory effects, we conducted molecular docking and molecular dynamics simulations. Interaction analysis revealed that both atropine and fabiatrin exhibit strong binding affinity and structural stability with COX-2. Subsequent ADMET (absorption, distribution, metabolism, excretion, and toxicity) predictions indicated that atropine and fabiatrin had favorable pharmacokinetic properties and low toxicity, suggesting their potential as anti-inflammatory agents. Notably, this is the first study to demonstrate the inhibitory effect of fabiatrin on COX-2. Overall, the integrated approach developed here provides an efficient and reliable strategy for identifying bioactive components from complex traditional Chinese medicine (TCM) systems, which may offer a new perspective and scientific basis for the research and development of naturally targeted drugs.</p>\\n </div>\",\"PeriodicalId\":8861,\"journal\":{\"name\":\"Biomedical Chromatography\",\"volume\":\"39 6\",\"pages\":\"\"},\"PeriodicalIF\":1.8000,\"publicationDate\":\"2025-04-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biomedical Chromatography\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/bmc.70092\",\"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":"Biomedical Chromatography","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/bmc.70092","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
Identification and Molecular Mechanism of COX-2 Inhibitors From Anisodus tanguticus: Ligand Fishing, In Vitro Validation, Molecular Docking, Molecular Dynamics, and ADMET Analysis
Anisodus tanguticus (Maxim.) Pascher has demonstrated remarkable inhibitory effects on cyclooxygenase-2 (COX-2); however, the effective substances and molecular mechanism remain ambiguous. In this study, surface plasmon resonance (SPR) ligand fishing technology coupled with UPLC-Q-TOF-MS analysis were applied to identify two COX-2 binders, atropine and fabiatrin, from A. tanguticus extracts. In vitro assays verified their potent COX-2 inhibitory effects, with IC50 values of 16.63 and 10.66 mM, respectively. To elucidate the molecular mechanism underlying their inhibitory effects, we conducted molecular docking and molecular dynamics simulations. Interaction analysis revealed that both atropine and fabiatrin exhibit strong binding affinity and structural stability with COX-2. Subsequent ADMET (absorption, distribution, metabolism, excretion, and toxicity) predictions indicated that atropine and fabiatrin had favorable pharmacokinetic properties and low toxicity, suggesting their potential as anti-inflammatory agents. Notably, this is the first study to demonstrate the inhibitory effect of fabiatrin on COX-2. Overall, the integrated approach developed here provides an efficient and reliable strategy for identifying bioactive components from complex traditional Chinese medicine (TCM) systems, which may offer a new perspective and scientific basis for the research and development of naturally targeted drugs.
期刊介绍:
Biomedical Chromatography is devoted to the publication of original papers on the applications of chromatography and allied techniques in the biological and medical sciences. Research papers and review articles cover the methods and techniques relevant to the separation, identification and determination of substances in biochemistry, biotechnology, molecular biology, cell biology, clinical chemistry, pharmacology and related disciplines. These include the analysis of body fluids, cells and tissues, purification of biologically important compounds, pharmaco-kinetics and sequencing methods using HPLC, GC, HPLC-MS, TLC, paper chromatography, affinity chromatography, gel filtration, electrophoresis and related techniques.