{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:46:41Z","timestamp":1782280001507,"version":"3.54.5"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Fine particulate matter (PM2.5, FPM) can induce and exacerbate chronic obstructive pulmonary disease (COPD) by triggering oxidative stress and multiple other pathogenic pathways. Our previous studies have demonstrated that Qingre\u2013Huatan\u2013Liqi formula (QRHTLQ) can improve the symptoms of patients with acute exacerbation of COPD (AECOPD), and animal experiments have suggested that QRHTLQ may prevent AECOPD via the EGFR\u2013PI3K\u2013AKT pathway. However, the protective effects and precise mechanisms by which QRHTLQ attenuates FPM-induced lung injury remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      FPM-induced lung injury models were established by repeated intratracheal instillations of FPM every 3\u00a0days. Thirty rats were randomly divided into control, model, low-dose QRHTLQ, medium-dose QRHTLQ, high-dose QRHTLQ, and erythromycin groups. The therapeutic effects of QRHTLQ were evaluated by H&amp;amp;E staining and qPCR. LC\u2013MS was used to identify blood-absorbed active constituents of QRHTLQ. Proteomics combined with network pharmacology was applied to identify key targets. The effects of QRHTLQ on these targets and related processes were validated by immunofluorescence, ELISA, and Western blot. Molecular docking and molecular dynamics simulations were performed to evaluate constituent\u2013target binding and complex stability.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , dHL-60 cells were stimulated with FPM to explore the intervention effects of QRHTLQ-containing serum and baicalin.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      QRHTLQ alleviated FPM-triggered airway inflammation, downregulated pulmonary IL-6, IL-1\u03b2, TNF-\u03b1 mRNA as well as ROS levels in bronchoalveolar lavage fluid (BALF). Six major blood-absorbed active constituents were identified using LC\u2013MS. Integrated analyses suggested that QRHTLQ interferes with neutrophil extracellular traps (NETs) formation, with MAPK14 (P38\u03b1, the major isoform of P38 MAPK) identified as a core target. QRHTLQ decreased PAD4 in BALF and lung tissue, reduced NETs levels in lung tissue, and decreased the p-P38\/P38 ratio. Baicalin exhibited the most favorable binding energy with MAPK14, and molecular dynamics simulations demonstrated that the baicalin\u2013P38 MAPK14 complex was structurally stable.\n                      <jats:italic>In vitro<\/jats:italic>\n                      experiments confirmed that baicalin significantly reduced NETs release in dHL-60 cells and downregulated the p-P38\/P38 ratio, thereby inhibiting MAPK14 activation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>QRHTLQ alleviates FPM-induced lung injury by modulating MAPK signaling and inhibiting NETs formation. Baicalin is likely a key blood-absorbed active component through which QRHTLQ exerts these protective effects.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1778590","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T04:51:59Z","timestamp":1782276719000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Qingre\u2013Huatan\u2013Liqi formula attenuates FPM-induced lung injury via modulation of MAPK signaling and NETs formation"],"prefix":"10.3389","volume":"17","author":[{"given":"Jie","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Traditional Chinese Medicine, Peking University People\u2019s Hospital","place":["Beijing, China"]},{"name":"Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqian","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine, Peking University People\u2019s Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufeng","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine, Peking University People\u2019s Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongtao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine, Peking University People\u2019s Hospital","place":["Beijing, China"]},{"name":"Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianqiang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine, Peking University People\u2019s Hospital","place":["Beijing, China"]},{"name":"Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuyi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Fuzhou University Affiliated Provincial Hospital","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuiling","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine, Peking University People\u2019s Hospital","place":["Beijing, China"]},{"name":"Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"106706","DOI":"10.1016\/j.envint.2021.106706","article-title":"Reduced ambient PM2.5, better lung function, and decreased risk of chronic obstructive pulmonary disease","volume":"156","author":"Bo","year":"2021","journal-title":"Environ. 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