{"title":"网络药理学、分子对接及体外验证探索大承气汤治疗脑出血的关键植物化学物质。","authors":"Yi-Zhi Yan, Xin-Yi Liu, Sha-Sha Yang, Shan-Shan Zhu, Ke Zhou, Qing Tian, Si-Jie Tan, Peng Zeng","doi":"10.2174/0115680266384135250714115903","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The development of secondary brain injury following intracerebral hemorrhage (ICH) involves multiple pathophysiological processes. Da-cheng-qi decoction (DCQD) has a long history of effectiveness in treating ICH and exhibits a variety of pharmacological effects. However, the phytochemicals and targets of DCQD targeting the pathophysiological processes of ICH still require further elucidation. This study aims to investigate the mechanism and key phytochemicals of DCQD in treating ICH based on the pathophysiological processes.</p><p><strong>Methods: </strong>We used the UHPLC-MS/MS method to identify the main phytochemicals of DCQD and evaluate their pharmacological and toxicological parameters. We obtained and systematically analyzed the action targets of the main phytochemicals of DCQD and screened the targets related to ICH key pathophysiological processes and the corresponding phytochemicals. The results of molecular docking, molecular dynamic simulations, the GEO database and in vitro validation experiments confirmed the results of network pharmacology.</p><p><strong>Results: </strong>The 20 main phytochemicals of DCQD interact with a total of 186 targets, with 75 targets specifically associated with the treatment of ICH identified through pathophysiological processes. Among them, chrysophanol 1-glucoside, aloe emodin, emodin, hesperidin, tangeritin, rhein and physcion were recognized as the potential phytochemicals of DCQD for the treatment of ICH. Neuroinflammation is a crucial factor in the development of secondary brain injury following ICH. Further analysis results suggest that targeting ferroptosis is one of the mechanisms by which DCQD regulates the pathophysiology processes of ICH to improve ICH. In vitro cell experiment results have demonstrated the regulatory effect of naringin on TNF-α and Cox2. In addition, the phytochemicals in DCQD also contribute to enhancement of cognitive function impaired by ICH.</p><p><strong>Conclusion: </strong>This study contributes to a better understanding of the underlying mechanisms behind DCQD's medicinal effects in treating ICH, offering insights into potential lead compounds for the development of anti-ICH drugs.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Network Pharmacology, Molecular Docking, and In vitro Validation to Explore the Key Phytochemicals of Da-cheng-qi Decoction Treating Intracerebral Hemorrhage.\",\"authors\":\"Yi-Zhi Yan, Xin-Yi Liu, Sha-Sha Yang, Shan-Shan Zhu, Ke Zhou, Qing Tian, Si-Jie Tan, Peng Zeng\",\"doi\":\"10.2174/0115680266384135250714115903\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The development of secondary brain injury following intracerebral hemorrhage (ICH) involves multiple pathophysiological processes. Da-cheng-qi decoction (DCQD) has a long history of effectiveness in treating ICH and exhibits a variety of pharmacological effects. However, the phytochemicals and targets of DCQD targeting the pathophysiological processes of ICH still require further elucidation. This study aims to investigate the mechanism and key phytochemicals of DCQD in treating ICH based on the pathophysiological processes.</p><p><strong>Methods: </strong>We used the UHPLC-MS/MS method to identify the main phytochemicals of DCQD and evaluate their pharmacological and toxicological parameters. We obtained and systematically analyzed the action targets of the main phytochemicals of DCQD and screened the targets related to ICH key pathophysiological processes and the corresponding phytochemicals. The results of molecular docking, molecular dynamic simulations, the GEO database and in vitro validation experiments confirmed the results of network pharmacology.</p><p><strong>Results: </strong>The 20 main phytochemicals of DCQD interact with a total of 186 targets, with 75 targets specifically associated with the treatment of ICH identified through pathophysiological processes. Among them, chrysophanol 1-glucoside, aloe emodin, emodin, hesperidin, tangeritin, rhein and physcion were recognized as the potential phytochemicals of DCQD for the treatment of ICH. Neuroinflammation is a crucial factor in the development of secondary brain injury following ICH. Further analysis results suggest that targeting ferroptosis is one of the mechanisms by which DCQD regulates the pathophysiology processes of ICH to improve ICH. In vitro cell experiment results have demonstrated the regulatory effect of naringin on TNF-α and Cox2. In addition, the phytochemicals in DCQD also contribute to enhancement of cognitive function impaired by ICH.</p><p><strong>Conclusion: </strong>This study contributes to a better understanding of the underlying mechanisms behind DCQD's medicinal effects in treating ICH, offering insights into potential lead compounds for the development of anti-ICH drugs.</p>\",\"PeriodicalId\":11076,\"journal\":{\"name\":\"Current topics in medicinal chemistry\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2025-07-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current topics in medicinal chemistry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2174/0115680266384135250714115903\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current topics in medicinal chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0115680266384135250714115903","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Network Pharmacology, Molecular Docking, and In vitro Validation to Explore the Key Phytochemicals of Da-cheng-qi Decoction Treating Intracerebral Hemorrhage.
Background: The development of secondary brain injury following intracerebral hemorrhage (ICH) involves multiple pathophysiological processes. Da-cheng-qi decoction (DCQD) has a long history of effectiveness in treating ICH and exhibits a variety of pharmacological effects. However, the phytochemicals and targets of DCQD targeting the pathophysiological processes of ICH still require further elucidation. This study aims to investigate the mechanism and key phytochemicals of DCQD in treating ICH based on the pathophysiological processes.
Methods: We used the UHPLC-MS/MS method to identify the main phytochemicals of DCQD and evaluate their pharmacological and toxicological parameters. We obtained and systematically analyzed the action targets of the main phytochemicals of DCQD and screened the targets related to ICH key pathophysiological processes and the corresponding phytochemicals. The results of molecular docking, molecular dynamic simulations, the GEO database and in vitro validation experiments confirmed the results of network pharmacology.
Results: The 20 main phytochemicals of DCQD interact with a total of 186 targets, with 75 targets specifically associated with the treatment of ICH identified through pathophysiological processes. Among them, chrysophanol 1-glucoside, aloe emodin, emodin, hesperidin, tangeritin, rhein and physcion were recognized as the potential phytochemicals of DCQD for the treatment of ICH. Neuroinflammation is a crucial factor in the development of secondary brain injury following ICH. Further analysis results suggest that targeting ferroptosis is one of the mechanisms by which DCQD regulates the pathophysiology processes of ICH to improve ICH. In vitro cell experiment results have demonstrated the regulatory effect of naringin on TNF-α and Cox2. In addition, the phytochemicals in DCQD also contribute to enhancement of cognitive function impaired by ICH.
Conclusion: This study contributes to a better understanding of the underlying mechanisms behind DCQD's medicinal effects in treating ICH, offering insights into potential lead compounds for the development of anti-ICH drugs.
期刊介绍：
Current Topics in Medicinal Chemistry is a forum for the review of areas of keen and topical interest to medicinal chemists and others in the allied disciplines. Each issue is solely devoted to a specific topic, containing six to nine reviews, which provide the reader a comprehensive survey of that area. A Guest Editor who is an expert in the topic under review, will assemble each issue. The scope of Current Topics in Medicinal Chemistry will cover all areas of medicinal chemistry, including current developments in rational drug design, synthetic chemistry, bioorganic chemistry, high-throughput screening, combinatorial chemistry, compound diversity measurements, drug absorption, drug distribution, metabolism, new and emerging drug targets, natural products, pharmacogenomics, and structure-activity relationships. Medicinal chemistry is a rapidly maturing discipline. The study of how structure and function are related is absolutely essential to understanding the molecular basis of life. Current Topics in Medicinal Chemistry aims to contribute to the growth of scientific knowledge and insight, and facilitate the discovery and development of new therapeutic agents to treat debilitating human disorders. The journal is essential for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important advances.
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