{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:05:27Z","timestamp":1790661927433,"version":"4.1.0"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT, South Korea","doi-asserted-by":"publisher","award":["2024-DD-RD-0015-02"],"award-info":[{"award-number":["2024-DD-RD-0015-02"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      This study was conducted to investigate the preventive effects of\n                      <jats:italic>Pimpinella brachycarpa<\/jats:italic>\n                      extract (PBE), which has demonstrated anti-inflammatory effects but whose molecular mechanisms and active components are not completely understood, in experimental periodontitis and to elucidate its underlying mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The protective effects of PBE were evaluated in a lipopolysaccharide (LPS)-induced periodontitis rat model by assessing histological changes, TRAP-positive osteoclast presence, and alveolar bone loss. Network pharmacology, protein\u2013protein interaction network analysis, KEGG pathway enrichment analysis, and molecular docking were performed to predict the potential targets and mechanisms of PBE. The anti-inflammatory effects of PBE were further investigated in RAW264.7 macrophages and human periodontal ligament fibroblasts (PDLFs). Inflammatory mediators, cytokines, matrix metalloproteinases (MMPs), and PI3K\/Akt\/NF-\u03baB signaling-related proteins were analyzed. Major constituents of PBE were identified using UPLC-QTOF-MS, and their anti-inflammatory activities were evaluated\n                      <jats:italic>in vitro<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PBE attenuated periodontal tissue destruction in LPS-induced periodontitis rats, as demonstrated by reduced inflammatory cell infiltration, decreased CEJ\u2013ABC distance, and suppression of TRAP-positive osteoclast presence. Network pharmacology analysis identified the PI3K\/Akt signaling pathway as a key target associated with the anti-inflammatory effects of PBE. In RAW264.7 macrophages, PBE significantly reduced the production of NO, PGE2, TNF-\u03b1, and IL-1\u03b2. In PDLFs, PBE suppressed IL-1\u03b2-induced production of PGE2, IL-6, and IL-1\u03b2 and downregulated the expression of MMP-3, MMP-8, and MMP-13. Furthermore, PBE inhibited the phosphorylation of PI3K, Akt, IKK, I\u03baB\u03b1, and NF-\u03baB p65. Chemical profiling identified chlorogenic acid, luteolin 7-O-glucuronide, apigenin 7-O-glucuronide, and luteolin 3\u2032-O-glucuronide as major constituents. Among these, flavonoid glucuronides exhibited stronger anti-inflammatory activities than chlorogenic acid\n                      <jats:italic>in vitro<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The present findings indicate that PBE exerts anti-inflammatory and tissue-protective effects in experimental models of periodontitis. The observed effects were associated with suppression of PI3K\/Akt\u2013NF-\u03baB signaling. In addition, flavonoid glucuronides identified in PBE exhibited anti-inflammatory activities\n                      <jats:italic>in vitro<\/jats:italic>\n                      . Further studies are required to clarify the contribution of individual constituents to the biological activity of PBE.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1902876","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:50:27Z","timestamp":1790661027000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Pimpinella brachycarpa extract attenuates periodontal inflammation by modulating the PI3K\/Akt\u2013NF-\u03baB signaling pathway"],"prefix":"10.3389","volume":"17","author":[{"given":"A. 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