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Yerba Mate (\n \n Ilex paraguariensis<\/jats:italic>\n <\/jats:styled-content>\n ,\n YM<\/jats:styled-content>\n ), a popular plant broadly consumed in South America, is rich in biologically active compounds known for their therapeutic potential. This study assessed\n Y<\/jats:styled-content>\n 's in\u00a0vitro cytocompatibility, anti\u2010osteoclastogenic and immunomodulatory effects on oral stem cells and macrophages, as well as its in\u00a0vivo potential to reduce\n AP<\/jats:styled-content>\n severity and systemic side effects.\n <\/jats:p>\n <\/jats:sec>\n \n Methodology<\/jats:title>\n \n In vitro, instant powdered YM was dissolved in distilled water, filtered and diluted in culture media to final concentrations ranging from 1 to 200\u2009\u03bcg\/\n mL<\/jats:styled-content>\n . Cell viability and pro\u2010inflammatory cytokine release (\n IL<\/jats:styled-content>\n \u20101\u03b1,\n IL<\/jats:styled-content>\n \u20106,\n TNF<\/jats:styled-content>\n \u2010\u03b1) were assessed in human exfoliated deciduous teeth stem cells. The\n NF<\/jats:styled-content>\n \u2010\n \u03baB<\/jats:styled-content>\n pathway and anti\u2010osteoclastogenic activity were evaluated using a luciferase reporter assay and\n TRAP<\/jats:styled-content>\n staining in\n RAW<\/jats:styled-content>\n 264.7. Forty male Wistar rats were divided into control (C),\n YM<\/jats:styled-content>\n \u2010treated(YM), AP\u2010induced (AP) and AP with YM treatment (\n AP<\/jats:styled-content>\n \u2009+\u2009\n YM<\/jats:styled-content>\n ).\n YM<\/jats:styled-content>\n treatment (20\u2009Mg\/Kg\/Day) was administered via gavage for 58\u2009days. AP was induced after 28\u2009days of\n YM<\/jats:styled-content>\n intake, and the animals were euthanised 30\u2009days later. In serum, systemic redox state was assessed via total antioxidant capacity (\n TAC<\/jats:styled-content>\n ) and thiobarbituric acid reactive substances (\n TBARS<\/jats:styled-content>\n ). Histological and immunohistochemical analyses evaluated inflammation, cytokine expression (\n TNF<\/jats:styled-content>\n \u2010\u03b1,\n IL<\/jats:styled-content>\n \u20106,\n IL<\/jats:styled-content>\n \u201010 and\n IL<\/jats:styled-content>\n \u201017) and bone resorption markers. Micro\u2010\n CT<\/jats:styled-content>\n quantified alveolar bone loss. Data were analysed at\n p<\/jats:italic>\n \u2009<\u20090.05.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n YM<\/jats:styled-content>\n treatment demonstrated significant anti\u2010inflammatory, antioxidant and bone\u2010protective effects. In\u00a0vitro,\n YM\u2010<\/jats:styled-content>\n supported cell viability, reduced\n TNF<\/jats:styled-content>\n \u2010\u03b1 and\n IL<\/jats:styled-content>\n \u20101\u03b1, inhibited\n NF<\/jats:styled-content>\n \u2010\n \u03baB<\/jats:styled-content>\n activation and suppressed osteoclastogenesis. In\u00a0vivo,\n YM<\/jats:styled-content>\n treatment restored systemic antioxidant capacity and reduced lipid peroxidation, mitigating\n AP<\/jats:styled-content>\n \u2010induced oxidative stress. Furthermore,\n YM<\/jats:styled-content>\n intake attenuated the local inflammatory response and reduced the bone resorptive activity associated with\n AP<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n In vitro,\n YM<\/jats:styled-content>\n suppressed pro\u2010inflammatory cytokines and\n NF<\/jats:styled-content>\n \u2010\n \u03baB<\/jats:styled-content>\n , inhibited osteoclastogenesis and was cytocompatible. In\u00a0vivo, it reversed\n AP<\/jats:styled-content>\n \u2010induced redox state and reduced inflammation and bone resorption, suggesting therapeutic promise.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/iej.70031","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T10:02:46Z","timestamp":1758016966000},"page":"91-104","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Yerba Mate (\n Ilex paraguariensis A. St.\u2010Hil.<\/i>\n ) Reduces Oxidative Stress and Bone Resorption in Apical Periodontitis"],"prefix":"10.1111","volume":"59","author":[{"given":"Carolina Sayuri","family":"Wajima","sequence":"first","affiliation":[{"name":"Department of Restorative Dentistry S\u00e3o Paulo State University (UNESP), School of Dentistry Ara\u00e7atuba Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"de Barros Morais Cardoso","sequence":"additional","affiliation":[{"name":"Department of Restorative Dentistry S\u00e3o Paulo State University (UNESP), School of Dentistry Ara\u00e7atuba Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3189-1542","authenticated-orcid":false,"given":"Caroline","family":"Anselmi","sequence":"additional","affiliation":[{"name":"Department of Morphology and Pediatric Dentistry S\u00e3o Paulo State University (UNESP), School of Dentistry Araraquara Brazil"},{"name":"Department of Cariology, Restorative Sciences, and Endodontics, School of Dentistry University of Michigan Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4125-8441","authenticated-orcid":false,"given":"Renan","family":"Dal\u2010Fabbro","sequence":"additional","affiliation":[{"name":"Department of Cariology, Restorative Sciences, and Endodontics, School of Dentistry University of Michigan Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murilo Catelani","family":"Ferraz","sequence":"additional","affiliation":[{"name":"Department of Animal Clinic, Surgery and Reproduction S\u00e3o Paulo State University (UNESP), School of Veterinary Ara\u00e7atuba Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiane Cantiga","family":"da Silva","sequence":"additional","affiliation":[{"name":"Department of Restorative Dentistry S\u00e3o Paulo State University (UNESP), School of 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