{"_":"Berberine alleviates biofilm-associated immune-inflammatory injury in -induced osteomyelitis: insights from network pharmacology and experimental validation.","i":["Staphylococcus aureus"]}
金黄色葡萄球菌（SA）诱导的骨髓炎（OM）是一种常见的骨科感染，以生物膜形成和持续性炎症为特征。小檗碱（BBR）是一种天然异喹啉生物碱，具有抗菌和抗炎活性。然而，其在OM中的治疗潜力及潜在机制尚不清楚。本研究探讨了BBR对SA诱导的OM的作用，并通过网络药理学和验证实验探索其潜在机制。建立SA生物膜模型，采用菌落形成单位（CFU）计数、光学显微镜和共聚焦激光扫描显微镜（CLSM）评估BBR对细菌存活和成熟生物膜结构的影响。建立SA诱导的OM小鼠模型，设立克林霉素（CLD）治疗组作为阳性抗生素对照，以评估BBR的抗菌疗效并评价该化合物的局限性。通过扫描电子显微镜（SEM）检查植入物表面的生物膜形成情况。采用酶联免疫吸附试验（ELISA）测定血清炎症介质，通过苏木精-伊红（H&E）染色评估植入物周围骨组织的组织病理学变化。运用网络药理学和分子对接技术识别靶点和通路，并通过Western blotting验证关键蛋白。BBR显著降低了生物膜内细菌活力并减少了CFU计数。显微镜观察显示，处理后生物膜结构被破坏，生物膜覆盖率降低。与未治疗的OM组相比，CLD对细菌载量的降低程度比BBR更为显著。BBR显著减轻了骨破坏，减少了植入物相关生物膜形成，降低了炎症细胞浸润，并改善了组织形态。ELISA结果显示，BBR显著降低了促炎介质水平。网络药理学确定前列腺素内过氧化物合酶2（PTGS2）为关键靶点，并涉及缺氧诱导因子1（HIF-1）信号通路。分子对接表明BBR与PTGS2之间具有良好的结合能力。Western blotting显示，BBR下调了感染组织中PTGS2和HIF-1α的表达。这些发现表明，BBR通过抗生物膜和抗炎活性对SA诱导的OM发挥保护作用。然而，其抗菌疗效弱于CLD，提示BBR不应被视为抗生素的替代品，而应作为生物膜相关骨髓炎的辅助治疗手段。
(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. An 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 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&E) staining. Network pharmacology and molecular docking were performed to identify targets and pathways, and key proteins were validated by Western blotting. BBR significantly reduced bacterial viability within biofilms and decreased CFU counts . Microscopic observations showed disrupted biofilm architecture and reduced biofilm coverage after treatment. , 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-1α expression in infected tissues. 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.
Xuan Deng, Lin Zhang, Jinglin Li, Fuyin Yang, Chengrui Peng, Jiaze Peng, et al. {"_":"Berberine alleviates biofilm-associated immune-inflammatory injury in -induced osteomyelitis: insights from network pharmacology and experimental validation.","i":["Staphylococcus aureus"]}. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1878634.
Xuan Deng, Lin Zhang, Jinglin Li, Fuyin Yang, Chengrui Peng, Jiaze Peng, et al (2026). {"_":"Berberine alleviates biofilm-associated immune-inflammatory injury in -induced osteomyelitis: insights from network pharmacology and experimental validation.","i":["Staphylococcus aureus"]}. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1878634
Xuan Deng, Lin Zhang, Jinglin Li, Fuyin Yang, Chengrui Peng, Jiaze Peng, et al. {"_":"Berberine alleviates biofilm-associated immune-inflammatory injury in -induced osteomyelitis: insights from network pharmacology and experimental validation.","i":["Staphylococcus aureus"]}[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1878634.
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