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Currently, there is a lack of effective adjuvant treatments to nonsurgical periodontal therapy offering strong antiresorptive properties. Tanshinone IIA (T\u2010IIA), a lipophilic compound derived from\n                      <jats:italic>Salvia miltiorrhiza<\/jats:italic>\n                      , exhibits various biological properties. This study investigates the antiresorptive activity of tanshinone as an adjuvant therapy for periodontitis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Forty 8\u2010week\u2010old male C57BL6\/J mice were randomly assigned to four experimental groups: control (C), periodontitis (P), T\u2010IIA, and sodium tanshinone IIA sulfonate (STS). The C group did not undergo experimental periodontitis, while the P, T\u2010IIA, and STS groups were induced with periodontitis by placing ligatures around the first maxillary molars bilaterally. Tanshinones (40\u00a0mg\/kg) were administered daily via oral gavage immediately following ligature placement for 10 days. The P group received only the vehicle solution. Microcomputed tomography (micro\u2010CT) and histological, immunohistochemical, and real\u2010time quantitative polymerase chain reaction (RT\u2010qPCR) analyses were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>T\u2010IIA and STS significantly reduced the infiltration of inflammatory cells in the connective tissue and increased the percentage of fibroblasts. This treatment also mitigated alveolar bone loss caused by ligature placement compared to the P group, enhancing bone mineral density and improving bone architectural parameters. The T\u2010IIA and STS groups effectively lowered the number of osteoclasts and significantly downregulated the production of IL\u20101\u03b2, IL\u201017, and MMP\u201013. The mRNA level of cathepsin K was significantly reduced in the STS group compared to the P and T\u2010IIA groups, whereas IL\u20101\u03b2, TNF\u2010\u03b1, and RANKL were not statistically different among groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings demonstrate that T\u2010IIA and STS prevent periodontitis\u2010induced bone loss by controlling inflammation and inhibiting osteoclastogenesis. This suggests that these compounds possess dual antiresorptive and anti\u2010inflammatory properties, making them promising novel therapeutic agents for treating periodontitis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain Language Summary<\/jats:title>\n                    <jats:p>Periodontitis is a serious gum disease that damages the bone supporting teeth, often leading to tooth loss. While current treatments aim to clean the affected areas, they do not always prevent further bone damage. In this study, we explored whether tanshinone IIA, a natural compound from a traditional medicinal plant, could offer extra protection against bone loss. We worked with mice to mimic human gum disease by placing small threads around their teeth to cause inflammation and bone loss. The mice were divided into four groups: one received no treatment, another had untreated periodontitis, and two groups were given different forms of tanshinone IIA for 10 days. We then examined their bones, tissues, and key markers of inflammation and bone damage. Mice treated with tanshinone IIA showed less inflammation, improved bone structure, and fewer cells that break down bone. The treatments also reduced harmful proteins linked to inflammation and tissue damage. These findings suggest that tanshinone IIA helps protect the bone by reducing inflammation and preventing excessive bone breakdown. Our research highlights tanshinone IIA as a potential new therapy for periodontitis. By targeting both inflammation and bone loss, this compound could be an interesting alternative to manage experimental periodontitis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jper.24-0618","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T14:43:13Z","timestamp":1752590593000},"page":"1138-1153","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Anti\u2010inflammatory and antiresorptive activities of tanshinone\u2010IIA mitigate alveolar bone destruction in mice with experimental periodontitis"],"prefix":"10.1002","volume":"96","author":[{"given":"Angelica Leticia Reis","family":"Pavanelli","sequence":"first","affiliation":[{"name":"Department of Diagnosis and Surgery, S\u00e3o Paulo State University School of Dentistry at Araraquara  Araraquara S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e2mmea Martins","family":"Vieira","sequence":"additional","affiliation":[{"name":"Department of Restorative Dentistry, S\u00e3o Paulo State University School of Dentistry at Araraquara  Araraquara S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila Chierici","family":"Marcantonio","sequence":"additional","affiliation":[{"name":"Department of Diagnosis and Surgery, S\u00e3o Paulo State University School of Dentistry at Araraquara  Araraquara S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisele","family":"Faria","sequence":"additional","affiliation":[{"name":"Department of Restorative Dentistry, S\u00e3o Paulo State University School of Dentistry at Araraquara  Araraquara S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sotirios","family":"Tetradis","sequence":"additional","affiliation":[{"name":"Division of Diagnostic and Surgical Sciences UCLA School of Dentistry  Los 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