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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-\u03b3, TNF-\u03b1), 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.<\/jats:p>","DOI":"10.3390\/antibiotics14070626","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T05:17:42Z","timestamp":1750396662000},"page":"626","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Antimicrobial and Immunomodulatory Effects of Punicalagin and Meropenem in a Murine Model of Sublethal Sepsis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3132-2267","authenticated-orcid":false,"given":"Liliane dos Santos","family":"Rodrigues","sequence":"first","affiliation":[{"name":"Graduate Program in Biodiversity and Biotechnology of the Amazon, Federal University of Maranh\u00e3o, S\u00e3o Lu\u00eds 65080-805, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3621-5364","authenticated-orcid":false,"given":"Priscila Mendon\u00e7a","family":"Mendes","sequence":"additional","affiliation":[{"name":"Graduate Program in Health Sciences, Federal University of Maranh\u00e3o, S\u00e3o Lu\u00eds 65080-805, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 Alvares Marques","family":"Vale","sequence":"additional","affiliation":[{"name":"Graduate Program in Health Sciences, Federal University of Maranh\u00e3o, S\u00e3o Lu\u00eds 65080-805, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7163-3831","authenticated-orcid":false,"given":"Jos\u00e9 Lima","family":"Pereira-Filho","sequence":"additional","affiliation":[{"name":"Graduate Program in Health Sciences, Federal University of Maranh\u00e3o, S\u00e3o Lu\u00eds 65080-805, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0567-2514","authenticated-orcid":false,"given":"Elizabeth Soares","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Department of Animal and Veterinary Sciences, Aarhus University, 8830 Tjele, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joicy Cortez de S\u00e1","family":"Sousa","sequence":"additional","affiliation":[{"name":"Pharmacy Department, Federal University of Maranh\u00e3o, S\u00e3o Lu\u00eds 65080-805, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8782-4923","authenticated-orcid":false,"given":"M\u00e1rcia Cristina Gon\u00e7alves","family":"Maciel","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Brasilia, Bras\u00edlia 70910-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2868-1314","authenticated-orcid":false,"given":"Val\u00e9rio","family":"Monteiro-Neto","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Brasilia, Bras\u00edlia 70910-900, Brazil"},{"name":"Health Sciences Center, Federal University of Maranh\u00e3o, S\u00e3o Lu\u00eds 65080-805, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.2147\/JIR.S302929","article-title":"Punicalagin inhibited inflammation and migration of fibroblast-like synoviocytes through NF-\u03baB pathway in the experimental study of rheumatoid arthritis","volume":"14","author":"Huang","year":"2021","journal-title":"J. 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