{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,4]],"date-time":"2025-10-04T00:45:18Z","timestamp":1759538718781,"version":"build-2065373602"},"reference-count":66,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013254","name":"National College Students Innovation and Entrepreneurship Training Program","doi-asserted-by":"publisher","award":["202210547026"],"award-info":[{"award-number":["202210547026"]}],"id":[{"id":"10.13039\/501100013254","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hunan Provincial Health Commission Foundatio","award":["D202303059375"],"award-info":[{"award-number":["D202303059375"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Sepsis and its related complication acute kidney injury (septic-AKI) are associated with high mortality and morbidity, and have become a global health challenge. Xuebijing (XBJ) injection prepared from five traditional Chinese medicines (TCM) is commonly used for clinical treatment of sepsis and septic-AKI. Yet, the underlying therapeutic mechanism of XBJ is remain elusive. This study aims to unveil the underlying mechanisms of XBJ in treating sepsis and septic-AKI.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>In this study, we used network pharmacology and molecular docking to screen the core drug-disease targets and predict the potential mechanism involving in XBJ against sepsis and septic AKI. Furthermore, <jats:italic>in vitro<\/jats:italic> experiments were performed to verify the predicted results and clarify the underlying mechanism.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Five hub targets including MMP9, TNF, IL-6, STAT3 and TP53 were identified by constructing and analyzing protein-protein interaction network. Eight key active components linking to five hub targets were also reversely screened. The results of gene ontology (GO) and pathway enrichment analysis showed that on the list of top 10 significant GO terms and pathways, most were inflammatory signaling pathways. The molecular docking results suggested that eight active components more preferentially bound to MMP9 and TNF\u03b1 with the highest affinity. <jats:italic>In vitro<\/jats:italic>, XBJ significantly decreased the mRNA and protein levels of IL-1\u03b2, IL-6, TNF\u03b1 and MMP9 in HEK-293 cells exposed to lipopolysaccharides (LPS).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>XBJ exerted therapeutic effects on sepsis and septic-AKI through suppression IL-1\u03b2\/MMP9, IL-6\/MMP9 and TNF\u03b1\/MMP9 at both mRNA and protein level. This study provides a pharmacological basis for further validating the therapeutic mechanism of XBJ in treating sepsis and septic-AKI by <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> experiments.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0333478","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T17:21:55Z","timestamp":1759512115000},"page":"e0333478","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Revealing the molecular mechanisms underlying Xuebijing against sepsis and septic acute kidney injury via bioinformatics and experimental approaches"],"prefix":"10.1371","volume":"20","author":[{"given":"Xing","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaiqi","family":"Ren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michal R.","family":"Baran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Le","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriel Mbuta","family":"Tchivelekete","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Bai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weijian","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3760-3019","authenticated-orcid":true,"given":"Xinhua","family":"Shu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,10,3]]},"reference":[{"issue":"8","key":"pone.0333478.ref001","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The Third International Consensus Definitions for Sepsis and Septic Shock 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