{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:02:07Z","timestamp":1790013727893,"version":"4.0.1"},"reference-count":44,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T00:00:00Z","timestamp":1719273600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Osteomyelitis is an invasive bone infection that can lead to severe pain and even disability, posing a challenge for orthopedic surgery. Naringin can reduce bone\u2010related inflammatory conditions. This study aimed to elucidate the function and mechanism of naringin in a <jats:italic>Staphylococcus aureus<\/jats:italic>\u2013induced mouse model of osteomyelitis. Femurs of <jats:italic>S. aureus<\/jats:italic>\u2013infected mice were collected after naringin administration and subjected to microcomputed tomography to analyze cortical bone destruction and bone loss. Bacterial growth in femurs was also assessed. Proinflammatory cytokine levels in mouse femurs were measured using enzyme\u2010linked immunosorbent assays. Pathological changes and bone resorption were analyzed using hematoxylin and eosin staining and tartrate\u2010resistant acid phosphatase staining, respectively. Quantitative\u00a0reverse transcription polymerase chain reaction and western blot analysis were used to quantify the messenger RNA and protein expression of osteogenic differentiation\u2013associated genes in the femurs. The viability of human bone marrow\u2013derived stem cells (hBMSCs) was determined using cell counting kit\u20108. Alizarin Red S staining and alkaline phosphatase staining were performed to assess the formation of mineralization nodules and bone formation in vitro. Notch signaling\u2013related protein levels in femur tissues and hBMSCs were assessed using western blot analysis. Experimental results revealed that naringin alleviated <jats:italic>S. aureus<\/jats:italic>\u2013induced cortical bone destruction and bone loss in mice by increasing the bone volume\/total volume ratio. Naringin suppressed <jats:italic>S. aureus<\/jats:italic>\u2013induced bacterial growth and inflammation in femurs. Moreover, it alleviated histopathological changes, inhibited bone resorption, and increased the expression of osteogenic markers in osteomyelitic mice. It increased the viability of hBMSCs and promoted their differentiation and bone mineralization in vitro. Furthermore, naringin activated Notch signaling by upregulating the protein levels of Notch1, Jagged1, and Hes1 in the femurs of model mice and <jats:italic>S. aureus<\/jats:italic>\u2013stimulated hBMSCs. In conclusion, naringin reduces bacterial growth, inflammation, and bone resorption while upregulating the expression of osteogenic markers in <jats:italic>S. aureus<\/jats:italic>\u2013infected mice and hBMSCs by activating Notch signaling.<\/jats:p>","DOI":"10.1002\/jbt.23753","type":"journal-article","created":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T12:51:18Z","timestamp":1719319878000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Naringin exerts antibacterial and anti\u2010inflammatory effects on mice with <i>Staphylococcus aureus<\/i>\u2013induced osteomyelitis"],"prefix":"10.1002","volume":"38","author":[{"given":"Rong","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Medicine, Xiangyang Central Hospital Affiliated Hospital of Hubei University of Arts and Science Xiangyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"NongXin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Xiangyang Central HospitaI Affiliated Hospital of Hubei University of Arts and Science Xiangyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3630-8424","authenticated-orcid":false,"given":"Dong'ang","family":"Zhan","sequence":"additional","affiliation":[{"name":"Department of Hospital Infection Management Office, Xiangyang Central Hospital Affiliated Hospital of Hubei University of Arts and Science Xiangyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5307-7071","authenticated-orcid":false,"given":"Fengwen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Xiangyang Central HospitaI Affiliated Hospital of Hubei University of Arts and Science Xiangyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,25]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1219895"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202206154"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jor.2016.10.004"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2015.00085"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1159\/000342449"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)61999-1"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2014.12.016"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiu386"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/femspd\/ftx123"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2017.00379"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/13880209.2016.1216131"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2011.09.034"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/rb\/rbad006"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2023.110344"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/1759720X20966135"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-015-8665-x"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2672.2011.05070.x"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.2338"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.60183"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.14082"},{"issue":"2","key":"e_1_2_8_22_1","first-page":"3328","volume":"17","author":"Huang D.","year":"2018","journal-title":"Mol. 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