Antimicrobial and Immunomodulatory Effects of Punicalagin and Meropenem in a Murine Model of Sublethal Sepsis

Background: Punicalagin (Pg), a major ellagitannin derived from pomegranates, possesses antimicrobial, antioxidant, and immunomodulatory properties, suggesting its potential as an adjunctive therapy for sepsis. Objectives: This study investigated the synergistic effects of punicalagin and meropenem in a murine model of sublethal sepsis induced by cecal ligation and puncture (CLP). Methods: Mice were treated with punicalagin and meropenem, and multiple parameters were analyzed, including hematological indices, bacterial burden, lymphoid organ cellularity, cytokine profiles (IL-2, IL-4, IL-6, IL-10, IL-17, IFN-γ, TNF-α), nitric oxide (NO) production, and organ histopathology. Results: Punicalagin enhanced NO-mediated antimicrobial responses, increased neutrophil migration, preserved lymphoid cellularity, and significantly reduced the bacterial translocation. Combined therapy with meropenem improved systemic IL-10 levels and mitigated histopathological damage in the liver, kidney, intestine, and lung. Importantly, punicalagin did not induce thrombocytopenia. Conclusions: These results support the potential of punicalagin as an adjunctive agent to antibiotics for sepsis treatment, offering both antimicrobial and immunoregulatory benefits. Further studies are required to explore its clinical applicability.