{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T19:49:30Z","timestamp":1785440970153,"version":"3.56.0"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"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>Sepsis is a life-threatening condition caused by a dysregulated host response to infection, characterized by biphasic immune dysregulation and high mortality rates. Artesunate (AS), a semisynthetic artemisinin derivative, has demonstrated broad pharmacological properties, yet its overall efficacy and mechanisms in sepsis remain systematically unassessed at the preclinical level.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>In this study, we aimed to conduct the first systematic review and meta-analysis to evaluate the therapeutic efficacy and underlying mechanisms of AS in animal models of sepsis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We systematically searched five electronic databases up to 3 September 2025, for controlled\n                      <jats:italic>in vivo<\/jats:italic>\n                      studies analyzing the effects of AS in septic animals. The study quality was assessed using the SYRCLE risk-of-bias tool, and evidence certainty was rated via the GRADE approach. Statistical analyses, including meta-analysis, publication bias, and sensitivity analyses, were performed using RevMan 5.4 and Stata 17.0.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Fifteen studies involving mice and rats were included. Meta-analysis indicated that AS was associated with improved survival (10 studies, OR: 6.87, 95% CI: 3.81\u201312.41,\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.00001), reduced bacterial load, and promotion of body weight recovery. Organ protection was evidenced by attenuated lung injury (reduced histological scores, MPO activity, and wet-to-dry ratio) and improved liver function (decreased AST and ALT levels). Analysis of cytokine data from different time-points suggested a potential phase-dependent immunomodulatory effect: AS suppressed pro-inflammatory cytokines (TNF-\u03b1 and IL-6) during the hyperinflammatory phase while restoring immune competence in the immunosuppressive phase, accompanied by elevated IL-1\u03b2. Furthermore, AS reduced apoptosis (decreased TUNEL-positive cells) and enhanced pro-survival signaling (increased p-mTOR\/mTOR ratio); however, its effect on caspase-3 was not significant. Sensitivity analyses supported the robustness of the primary findings, and no significant publication bias was detected within the limits of the available studies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>AS is associated with survival benefits and multi-organ protection in septic animal models through multimodal mechanisms, potential phase-aware immunomodulation, antiapoptotic effects, and enhanced bacterial clearance. Despite methodological heterogeneity across studies, these preclinical findings support further investigation of AS as a potential therapeutic candidate for sepsis treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic Review Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/PROSPERO\/view\/CRD420251146068<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1748083","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T06:44:03Z","timestamp":1769582643000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The efficacy of artesunate in animal models of sepsis: a systematic review and meta-analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Wenzhan","family":"Xie","sequence":"first","affiliation":[{"name":"Center of Smart Laboratory and Molecular Medicine, School of Medicine, Chongqing University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linxi","family":"Lv","sequence":"additional","affiliation":[{"name":"Center of Smart Laboratory and Molecular Medicine, School of Medicine, Chongqing University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, First Affiliated Hospital, Army Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialong","family":"Wei","sequence":"additional","affiliation":[{"name":"Center of Smart Laboratory and Molecular Medicine, School of Medicine, Chongqing University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanshan","family":"Gui","sequence":"additional","affiliation":[{"name":"Center of Smart Laboratory and Molecular Medicine, School of Medicine, Chongqing University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Han","sequence":"additional","affiliation":[{"name":"Center of Smart Laboratory and Molecular Medicine, School of Medicine, Chongqing University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laixian","family":"Zhou","sequence":"additional","affiliation":[{"name":"Center of Smart Laboratory and Molecular Medicine, School of Medicine, Chongqing University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Feng","sequence":"additional","affiliation":[{"name":"Center of Smart Laboratory and Molecular Medicine, School of Medicine, Chongqing University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Gu","sequence":"additional","affiliation":[{"name":"Center of Smart Laboratory and Molecular Medicine, School of Medicine, Chongqing University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s12963-018-0160-x","article-title":"Epidemiological trends of sepsis in the twenty-first century (2000-2013): an analysis of incidence, mortality, and associated costs in Spain","volume":"16","author":"\u00c1lvaro-Meca","year":"2018","journal-title":"Popul. 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