{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:20:27Z","timestamp":1792790427346,"version":"4.5.0"},"reference-count":95,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"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. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Acute graft-versus-host disease (aGVHD) remains a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study investigated the preventive effects of paeoniflorin (PF), a natural monoterpene glycoside, on aGVHD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Candidate herb-derived compounds against aGVHD were screened using SymMap, HERB, ADMETlab, and InflamNat, followed by molecular docking. The preventive effects of PF were evaluated in major histocompatibility complex (MHC)-mismatched murine aGVHD models. An entire-process paeoniflorin (EP-PF) regimen, involving donor pretreatment before transplantation and recipient treatment after transplantation, was proposed for enhancing the preventive effect. Survival, body weight, clinical score, hematopoietic reconstitution, donor T cell infiltration, cytokine and chemokine levels, gut injury, apoptosis, gut microbiota, transcriptomic changes, and graft-versus-tumor (GVT) activity were assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PF was identified as a promising multi-target compound for aGVHD prevention. PF reduced clinical severity, body weight loss, and mortality, while improving hematopoietic recovery and increasing hematopoietic stem\/progenitor cell (HSPC) numbers. EP-PF regimen showed stronger protection than recipient-only PF administration. Mechanistically, EP-PF reduced intestinal donor cluster of differentiation 4 (CD4) positive and cluster of differentiation 8 (CD8) positive T cell infiltration, partially restored CD4\n                      <jats:sup>+<\/jats:sup>\n                      \/CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell balance, and reversed inflammatory transcriptional programs in donor T cells. Moreover, EP-PF balanced serum levels of cytokines and chemokines, preserved gut barrier integrity, reduced intestinal apoptosis, and partially corrected gut microbiota dysbiosis. Importantly, EP-PF preserved donor cell-mediated tumor control in a green fluorescent protein (GFP)-labeled A20 GVT model. PF also directly inhibited the proliferation of hematologic tumor cells and promoted their apoptosis\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>PF prevents experimental aGVHD through coordinated regulation of donor T cell responses, inflammatory mediators, hematopoietic reconstitution, intestinal barrier injury, apoptosis, and gut microbiota, while preserving GVT activity. These findings support PF as a potential prophylactic candidate for allo-HSCT.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1937379","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T04:25:50Z","timestamp":1788841550000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Paeoniflorin prevents acute graft-versus-host disease while preserving graft-versus-tumor effects"],"prefix":"10.3389","volume":"17","author":[{"given":"Xingyu","family":"Wan","sequence":"first","affiliation":[{"name":"Medical Center of Hematology, Xinqiao Hospital of Army Medical University","place":["Chongqing, China"]},{"name":"Chongqing Key Laboratory of Hematology and Microenvironment","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Li","sequence":"additional","affiliation":[{"name":"Medical Center of Hematology, Xinqiao 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Hematology, Xinqiao Hospital of Army Medical University","place":["Chongqing, China"]},{"name":"Chongqing Key Laboratory of Hematology and Microenvironment","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Medical Center of Hematology, Xinqiao Hospital of Army Medical University","place":["Chongqing, China"]},{"name":"Chongqing Key Laboratory of Hematology and Microenvironment","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuiqing","family":"Liu","sequence":"additional","affiliation":[{"name":"Medical Center of Hematology, Xinqiao Hospital of Army Medical University","place":["Chongqing, China"]},{"name":"Chongqing Key Laboratory of Hematology and Microenvironment","place":["Chongqing, 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