{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:14:58Z","timestamp":1772118898691,"version":"3.50.1"},"reference-count":32,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T00:00:00Z","timestamp":1739836800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Rapid Comm Mass Spectrometry"],"published-print":{"date-parts":[[2025,5,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>\n                      Protopine, an active alkaloid in\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>Papaver somniferum<\/jats:italic>\n                      <\/jats:styled-content>\n                      L., was abundant in a well\u2010known anticough traditional Chinese medicine preparation\u2014Zhi\u2010Ke\u2010Bao tablets. Till now, the metabolism feature and anticough mechanism of protopine have not been fully elucidated, restricting its further development.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The metabolites of protopine in rats were profiled by using ultra\u2010high performance liquid chromatography coupled with time\u2010of\u2010flight mass spectrometry, and its anticough targets and mechanism were predicted by network pharmacology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In rats, a total of 19 metabolites were identified following ingestion of protopine (21\u2009mg\/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\u2010opening, methylation, demethylation, glucuronidation, sulfation, and hydroxylation. Among them, methylation, sulfation, and hydroxylation of protopine in\u00a0vivo 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\u2010Akt signaling pathway, FoxO signaling pathway, and TNF signaling pathway, etc.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The metabolic features of protopine and its potential mechanisms for anticough effects were outlined, providing data for further anticough pharmacological validation of protopine.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/rcm.10012","type":"journal-article","created":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T01:47:16Z","timestamp":1739929636000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Combination of Metabolite Analysis and Network Pharmacology to Explore the Potential Anticough Mechanism of Protopine\u2014A Marker in Zhi\u2010Ke\u2010Bao Tablets"],"prefix":"10.1002","volume":"39","author":[{"given":"Qi\u2010Feng","family":"Zou","sequence":"first","affiliation":[{"name":"State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Science Guangxi Normal University  Guilin People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"De\u2010Jian","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine South China Agricultural University  Guangzhou People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng\u2010Jun","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Science Guangxi Normal University  Guilin People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zi\u2010Hao","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Science Guangxi Normal University  Guilin People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xia","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Science Guangxi Normal University  Guilin People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong\u2010Huang","family":"Xu","sequence":"additional","affiliation":[{"name":"Teyi Pharmaceutical Group Co., Ltd.  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