{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:07:18Z","timestamp":1790140038826,"version":"4.0.1"},"reference-count":97,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"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>Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) contributes substantially to morbidity and mortality. Andrographolide derivative injections (e.g., Xiyanping, Yanhuning, Chuanhuning, Lianbizhi) are widely used adjunctive treatments in China. Their clinical efficacy remains unclear, and we explored the potential mechanisms of the parent compound andrographolide in this study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A systematic review and meta-analysis of 32 randomized controlled trials (n = 2,668) comparing andrographolide derivatives plus conventional therapy versus conventional therapy alone in patients with AECOPD was conducted. Pulmonary function (FEV\n                      <jats:sub>1<\/jats:sub>\n                      %, FEV\n                      <jats:sub>1<\/jats:sub>\n                      , FVC), arterial oxygen tension (PaO\n                      <jats:sub>2<\/jats:sub>\n                      ), inflammatory markers (CRP, WBC, NEUT%, PCT), and overall clinical response were evaluated. Network pharmacology, molecular docking, and\n                      <jats:italic>in vitro<\/jats:italic>\n                      experiments using LPS-stimulated BEAS-2B cells were performed to explore underlying mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Adjunctive andrographolide derivatives significantly improved overall clinical response rate [RR = 1.21, 95% CI 1.17\u20131.26, P &amp;lt; 0.00001], FEV\n                      <jats:sub>1<\/jats:sub>\n                      % [MD = 6.48, 95% CI 3.52\u20139.45], FEV\n                      <jats:sub>1<\/jats:sub>\n                      [MD = 0.30\u00a0L, 95% CI 0.20\u20130.40], FVC [MD = 0.28\u00a0L, 95% CI 0.10\u20130.46], and PaO\n                      <jats:sub>2<\/jats:sub>\n                      [MD = 6.56\u00a0mmHg, 95% CI 4.68\u20138.45]. Inflammatory markers were also reduced: CRP [MD = \u22124.72\u00a0mg\/L, 95% CI -6.83 to \u20132.61], WBC [MD = \u22121.30 \u00d710\n                      <jats:sup>9<\/jats:sup>\n                      \/L, 95% CI \u22121.79 to \u22120.80], NEUT% [MD = \u22124.36 percentage points, 95% CI -6.18 to \u22122.54], PCT [MD = \u22120.17\u00a0ng\/mL, 95% CI -0.23 to \u22120.10] (all P &amp;lt; 0.0001). Network pharmacology identified 39 overlapping targets, highlighting TNF, IL-1\u03b2, NLRP3, and CASP1 as core targets. Molecular docking suggested energetically favorable predicted interactions of andrographolide with NLRP3, caspase-1, IL-1\u03b2, and IL-18.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , andrographolide enhanced BEAS-2B cell viability, reduced LDH release, and suppressed NLRP3, caspase-1, IL-1\u03b2, and TNF-\u03b1 expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Andrographolide derivative injections as adjunctive therapy may improve clinical response, pulmonary function, oxygenation, and inflammatory status in patients with AECOPD. Mechanistic experiments using the parent compound andrographolide suggest that these therapeutic effects are potentially mediated by the NLRP3\/caspase-1\/IL-1\u03b2 inflammatory axis. Nevertheless, these findings should be interpreted cautiously given the exclusively Chinese single-center RCTs, substantial heterogeneity in some outcomes, and lack of direct mechanistic data on individual derivatives.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1915339","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T04:46:01Z","timestamp":1790138761000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and mechanisms of andrographolide derivative in acute exacerbations of chronic obstructive pulmonary disease: a meta-analysis, network pharmacology, molecular docking, and in vitro validation study"],"prefix":"10.3389","volume":"17","author":[{"given":"Jiaxiang","family":"Li","sequence":"first","affiliation":[{"name":"Graduate School, Hebei University of Chinese Medicine","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowen","family":"Wu","sequence":"additional","affiliation":[{"name":"Graduate School, Hebei University of Chinese Medicine","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuning","family":"Shen","sequence":"additional","affiliation":[{"name":"Graduate School, Hebei University of Chinese Medicine","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayang","family":"Yao","sequence":"additional","affiliation":[{"name":"Graduate School, Hebei University of Chinese Medicine","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyue","family":"Yu","sequence":"additional","affiliation":[{"name":"Graduate School, Hebei University of Chinese Medicine","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Gao","sequence":"additional","affiliation":[{"name":"Graduate School, Hebei University of Chinese Medicine","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihao","family":"Gao","sequence":"additional","affiliation":[{"name":"Graduate School, Hebei University of Chinese Medicine","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limei","family":"Geng","sequence":"additional","affiliation":[{"name":"Graduate School, Hebei University of Chinese Medicine","place":["Shijiazhuang, Hebei, China"]},{"name":"Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Hebei University of Chinese Medicine","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"887","DOI":"10.3390\/cimb43020063","article-title":"Protective role of genetic variants in HSP90 genes-complex in COPD secondary to biomass-burning smoke exposure and non-severe COPD forms in tobacco smoking subjects","volume":"43","author":"Ambrocio-Ortiz","year":"2021","journal-title":"Curr. 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