{"title":"代谢物分析与网络药理学相结合探讨止咳宝片中丙托碱- a标记物的潜在抗咳机制","authors":"Qi-Feng Zou, De-Jian Chen, Cheng-Jun Liu, Zi-Hao Chen, Xia Yang, Rong-Huang Xu, Zhen-Hui Zhou, Jian-Xin Chen, Wei Shi, Feng-Xiang Zhang","doi":"10.1002/rcm.10012","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Rationale</h3>\n \n <p>Protopine, an active alkaloid in <i>Papaver somniferum</i> L., was abundant in a well-known anticough traditional Chinese medicine preparation—Zhi-Ke-Bao tablets. Till now, the metabolism feature and anticough mechanism of protopine have not been fully elucidated, restricting its further development.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>The metabolites of protopine in rats were profiled by using ultra-high performance liquid chromatography coupled with time-of-flight mass spectrometry, and its anticough targets and mechanism were predicted by network pharmacology.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>In rats, a total of 19 metabolites were identified following ingestion of protopine (21 mg/kg/day, i.g.), including 4 in plasma, 6 in urine, 5 in feces, 10 in liver, 2 in spleen, 4 in lung, 3 in kidney, 3 in heart, and 3 in brain. The main metabolic features were ring-opening, methylation, demethylation, glucuronidation, sulfation, and hydroxylation. Among them, methylation, sulfation, and hydroxylation of protopine in vivo were revealed for the first time. The network pharmacology results show that protopine and its metabolites regulate physiological activities by acting on STAT3, SRC, CASP3, MTOR, MMP9, ESR1, and other targets, involving PI3K-Akt signaling pathway, FoxO signaling pathway, and TNF signaling pathway, etc.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>The metabolic features of protopine and its potential mechanisms for anticough effects were outlined, providing data for further anticough pharmacological validation of protopine.</p>\n </section>\n </div>","PeriodicalId":225,"journal":{"name":"Rapid Communications in Mass Spectrometry","volume":"39 10","pages":""},"PeriodicalIF":1.8000,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Combination of Metabolite Analysis and Network Pharmacology to Explore the Potential Anticough Mechanism of Protopine—A Marker in Zhi-Ke-Bao Tablets\",\"authors\":\"Qi-Feng Zou, De-Jian Chen, Cheng-Jun Liu, Zi-Hao Chen, Xia Yang, Rong-Huang Xu, Zhen-Hui Zhou, Jian-Xin Chen, Wei Shi, Feng-Xiang Zhang\",\"doi\":\"10.1002/rcm.10012\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Rationale</h3>\\n \\n <p>Protopine, an active alkaloid in <i>Papaver somniferum</i> L., was abundant in a well-known anticough traditional Chinese medicine preparation—Zhi-Ke-Bao tablets. Till now, the metabolism feature and anticough mechanism of protopine have not been fully elucidated, restricting its further development.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>The metabolites of protopine in rats were profiled by using ultra-high performance liquid chromatography coupled with time-of-flight mass spectrometry, and its anticough targets and mechanism were predicted by network pharmacology.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>In rats, a total of 19 metabolites were identified following ingestion of protopine (21 mg/kg/day, i.g.), including 4 in plasma, 6 in urine, 5 in feces, 10 in liver, 2 in spleen, 4 in lung, 3 in kidney, 3 in heart, and 3 in brain. The main metabolic features were ring-opening, methylation, demethylation, glucuronidation, sulfation, and hydroxylation. Among them, methylation, sulfation, and hydroxylation of protopine in vivo were revealed for the first time. The network pharmacology results show that protopine and its metabolites regulate physiological activities by acting on STAT3, SRC, CASP3, MTOR, MMP9, ESR1, and other targets, involving PI3K-Akt signaling pathway, FoxO signaling pathway, and TNF signaling pathway, etc.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>The metabolic features of protopine and its potential mechanisms for anticough effects were outlined, providing data for further anticough pharmacological validation of protopine.</p>\\n </section>\\n </div>\",\"PeriodicalId\":225,\"journal\":{\"name\":\"Rapid Communications in Mass Spectrometry\",\"volume\":\"39 10\",\"pages\":\"\"},\"PeriodicalIF\":1.8000,\"publicationDate\":\"2025-02-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Rapid Communications in Mass Spectrometry\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/rcm.10012\",\"RegionNum\":3,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"BIOCHEMICAL RESEARCH METHODS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Rapid Communications in Mass Spectrometry","FirstCategoryId":"92","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/rcm.10012","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
Combination of Metabolite Analysis and Network Pharmacology to Explore the Potential Anticough Mechanism of Protopine—A Marker in Zhi-Ke-Bao Tablets
Rationale
Protopine, an active alkaloid in Papaver somniferum L., was abundant in a well-known anticough traditional Chinese medicine preparation—Zhi-Ke-Bao tablets. Till now, the metabolism feature and anticough mechanism of protopine have not been fully elucidated, restricting its further development.
Methods
The metabolites of protopine in rats were profiled by using ultra-high performance liquid chromatography coupled with time-of-flight mass spectrometry, and its anticough targets and mechanism were predicted by network pharmacology.
Results
In rats, a total of 19 metabolites were identified following ingestion of protopine (21 mg/kg/day, i.g.), including 4 in plasma, 6 in urine, 5 in feces, 10 in liver, 2 in spleen, 4 in lung, 3 in kidney, 3 in heart, and 3 in brain. The main metabolic features were ring-opening, methylation, demethylation, glucuronidation, sulfation, and hydroxylation. Among them, methylation, sulfation, and hydroxylation of protopine in vivo were revealed for the first time. The network pharmacology results show that protopine and its metabolites regulate physiological activities by acting on STAT3, SRC, CASP3, MTOR, MMP9, ESR1, and other targets, involving PI3K-Akt signaling pathway, FoxO signaling pathway, and TNF signaling pathway, etc.
Conclusions
The metabolic features of protopine and its potential mechanisms for anticough effects were outlined, providing data for further anticough pharmacological validation of protopine.
期刊介绍：
Rapid Communications in Mass Spectrometry is a journal whose aim is the rapid publication of original research results and ideas on all aspects of the science of gas-phase ions; it covers all the associated scientific disciplines. There is no formal limit on paper length ("rapid" is not synonymous with "brief"), but papers should be of a length that is commensurate with the importance and complexity of the results being reported. Contributions may be theoretical or practical in nature; they may deal with methods, techniques and applications, or with the interpretation of results; they may cover any area in science that depends directly on measurements made upon gaseous ions or that is associated with such measurements.
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