{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T08:22:47Z","timestamp":1787386967920,"version":"build-2736575974"},"reference-count":37,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:00:00Z","timestamp":1787356800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:00:00Z","timestamp":1787356800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFC3502605"],"award-info":[{"award-number":["2023YFC3502605"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytochemical Analysis"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Qingfei Jiedu Huatan Formula (QJHF) is a traditional Chinese medicine formula developed for severe pneumonia with the syndrome of \u201cphlegm heat obstructing the lung.\u201d<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>This study aimed to investigate the protective effects and underlying mechanisms of QJHF on pulmonary vascular endothelial barrier dysfunction in severe pneumonia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      Mouse models of pneumonia\/lung injury were established by intratracheal instillation of\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                      <\/jats:styled-content>\n                      or LPS to evaluate the protective effects of QJHF. A novel strategy integrating LC\u2013MS\u2010based serum pharmacochemistry and single\u2010cell RNA sequencing was performed to elucidate the underlying mechanisms of QJHF. An LPS\u2010induced HUVEC endothelial barrier injury model was used to screen active compounds and investigate their mechanisms of action.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      QJHF markedly alleviated lung injury and inflammatory responses in mice challenged with\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                      <\/jats:styled-content>\n                      or LPS. Specifically, QJHF reduced inflammatory cell infiltration, particularly neutrophil accumulation, decreased the levels of IL\u20101\u03b2, IL\u20106, and TNF\u2010\u03b1, and suppressed pulmonary myeloperoxidase activity. Single\u2010cell transcriptomic analysis revealed that QJHF mainly modulated inflammatory responses and vascular endothelial function. Moreover, QJHF decreased the lung index, lung wet\/dry weight ratio, total protein concentration, and Evans blue extravasation, while restoring VE\u2010cadherin expression, indicating preservation of pulmonary endothelial barrier integrity. Integrated serum component profiling and network pharmacology analyses identified 10 major absorbed constituents that may underlie the endothelial barrier\u2010protective effects of QJHF. Among these constituents, ginsenoside Rb1 (G\u2010Rb1) was identified as a key bioactive component. G\u2010Rb1 upregulated VE\u2010cadherin expression and protected endothelial barrier integrity both in\u00a0vitro and in\u00a0vivo and further ameliorated LPS\u2010induced lung tissue injury and inflammatory responses in mice. Target identification further implicated plasminogen activator inhibitor\u20101 (PAI\u20101) as a putative molecular target of G\u2010Rb1, which was subsequently validated by molecular dynamics simulations, cellular thermal shift assays, and surface plasmon resonance analysis. Importantly, PAI\u20101 overexpression attenuated the protective effects of G\u2010Rb1 on endothelial barrier function.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>QJHF ameliorates inflammatory lung injury in pneumonia mice by preserving the pulmonary vascular endothelial barrier. This effect is at least partly mediated by G\u2010Rb1, which targets and suppresses PAI\u20101, thereby restoring VE\u2010cadherin\u2010mediated endothelial junction integrity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pca.70087","type":"journal-article","created":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T07:27:12Z","timestamp":1787383632000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["LC\u2013MS\u2010Guided Identification of Bioactive Constituents in Qingfei Jiedu Huatan Formula Reveals Ginsenoside Rb1 as an Endothelial Barrier\u2010Protective Compound Targeting PAI\u20101 in Pneumonia"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0899-7303","authenticated-orcid":false,"given":"Peng","family":"Zhao","sequence":"first","affiliation":[{"name":"Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co\u2010constructed by Henan Province &amp; Education Ministry of P.R. China\/Henan Key Laboratory of Chinese Medicine for Respiratory Diseases Henan University of Chinese Medicine  Zhengzhou China"},{"name":"Lung Disease Diagnosis and Treatment Center, National Medical Center The First Affiliated Hospital of Henan University of Chinese Medicine  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinguang","family":"Liu","sequence":"additional","affiliation":[{"name":"Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co\u2010constructed by Henan Province &amp; Education Ministry of P.R. China\/Henan Key Laboratory of Chinese Medicine for Respiratory Diseases Henan University of Chinese Medicine  Zhengzhou China"},{"name":"Lung Disease Diagnosis and Treatment Center, National Medical Center The First Affiliated Hospital of Henan University of Chinese Medicine  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxiang","family":"Xing","sequence":"additional","affiliation":[{"name":"Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co\u2010constructed by Henan Province &amp; Education Ministry of P.R. China\/Henan Key Laboratory of Chinese Medicine for Respiratory Diseases Henan University of Chinese Medicine  Zhengzhou China"},{"name":"Lung Disease Diagnosis and Treatment Center, National Medical Center The First Affiliated Hospital of Henan University of Chinese Medicine  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co\u2010constructed by Henan Province &amp; Education Ministry of P.R. China\/Henan Key Laboratory of Chinese Medicine for Respiratory Diseases Henan University of Chinese Medicine  Zhengzhou China"},{"name":"Lung Disease Diagnosis and Treatment Center, National Medical Center The First Affiliated Hospital of Henan University of Chinese Medicine  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Furong","family":"Jia","sequence":"additional","affiliation":[{"name":"Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co\u2010constructed by Henan Province &amp; Education Ministry of P.R. 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