{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T05:04:59Z","timestamp":1783919099046,"version":"3.55.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"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>\n                      <jats:italic>Staphylococcus aureus<\/jats:italic>\n                      (SA)-induced osteomyelitis (OM) is a common orthopedic infection characterized by biofilm formation and persistent inflammation. Berberine (BBR), a natural isoquinoline alkaloid, exhibits antibacterial and anti-inflammatory activities. However, its therapeutic potential in OM and underlying mechanisms remain unclear. This study investigated the effects of BBR against SA-induced OM and explored potential mechanisms through network pharmacology and validation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      An\n                      <jats:italic>in vitro<\/jats:italic>\n                      SA biofilm model was established to assess the effects of BBR on bacterial survival and mature biofilm structure using colony-forming unit (CFU) counting, light microscopy, and confocal laser scanning microscopy (CLSM). A mouse model of SA-induced OM was established. A clindamycin (CLD)-treated group was included\n                      <jats:italic>in vivo<\/jats:italic>\n                      as a positive antibiotic comparator to benchmark the antibacterial efficacy of BBR and assess the limitations of this compound. Biofilm formation on implants was examined by scanning electron microscopy (SEM). Serum inflammatory mediators were measured by enzyme-linked immunosorbent assay (ELISA), and histopathological changes in peri-implant bone were evaluated by hematoxylin and eosin (H&amp;amp;E) staining. Network pharmacology and molecular docking were performed to identify targets and pathways, and key proteins were validated by Western blotting.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      BBR significantly reduced bacterial viability within biofilms and decreased CFU counts\n                      <jats:italic>in vitro<\/jats:italic>\n                      . Microscopic observations showed disrupted biofilm architecture and reduced biofilm coverage after treatment.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , compared with the untreated OM group, CLD produced a more pronounced reduction in bacterial load than BBR. BBR significantly alleviated bone destruction, reduced implant-associated biofilm formation, decreased inflammatory cell infiltration, and improved tissue morphology. ELISA results showed that BBR markedly reduced pro-inflammatory mediator levels. Network pharmacology identified prostaglandin-endoperoxide synthase 2 (PTGS2) as a key target and implicated the hypoxia-inducible factor 1 (HIF-1) signaling pathway. Molecular docking indicated favorable binding between BBR and PTGS2. Western blotting showed that BBR downregulated PTGS2 and HIF-1\u03b1 expression in infected tissues.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings suggest that BBR exerts protective effects against SA-induced OM through antibiofilm and anti-inflammatory activities. However, its antibacterial efficacy was weaker than that of CLD, indicating that BBR should not be regarded as a replacement for antibiotics but rather as an adjunctive therapy for biofilm-associated osteomyelitis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1878634","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T04:24:09Z","timestamp":1783916649000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Berberine alleviates biofilm-associated immune-inflammatory injury in Staphylococcus aureus-induced osteomyelitis: insights from network pharmacology and experimental validation"],"prefix":"10.3389","volume":"17","author":[{"given":"Xuan","family":"Deng","sequence":"first","affiliation":[{"name":"Department of Orthopedics, Affiliated Hospital of Zunyi Medical University","place":["Zunyi, 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