ArticleFrontiers in immunology2026
Paeoniflorin prevents acute graft-versus-host disease while preserving graft-versus-tumor effects.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: 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. Methods: 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. Results: 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 Conclusions: 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.
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