Chrysanthemum lavandulifolium Essential Oil Attenuates Periodontitis via Antibacterial and Anti-Inflammatory Effects

Periodontitis, driven by Porphyromonas gingivalis (P. gingivalis) biofilms, is a global health burden with limited treatment options due to antibiotic resistance. Chrysanthemum lavandulifolium is traditionally used in China for clearing heat and reducing swelling, yet its anti-periodontitis potential remains uncharacterized. This study evaluated the antibacterial and therapeutic effects of its essential oil (CLEO) against periodontitis. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of CLEO against P. gingivalis were determined by broth microdilution. Anti-biofilm activity was assessed via XTT assay. Network pharmacology, molecular docking, and 100 ns molecular dynamics simulations were employed to identify active compounds and core targets. Experimental periodontitis was induced in C57BL/6 mice by molar ligation. Mice received topical CLEO at concentrations of 2, 3, and 4 mg/mL, 2% minocycline, or vehicle once daily for 14 days. Periodontal inflammation, alveolar bone loss, collagen organization, osteoclast activity, and serum levels of MMP-9 and COX-2 were evaluated. CLEO exhibited potent anti-P. gingivalis activity, with an MIC of 2 mg/mL and MBC of 4 mg/mL. At the MIC, CLEO disrupted 57.5% of pre-formed P. gingivalis biofilms. Network pharmacology and molecular docking identified α-bisabolol, chamazulene, and 1,8-cineole as key active compounds, with the chamazulene-HSP90AA1 complex showing the strongest binding affinity (−10.0 kcal/mol). The 100 ns MD simulation confirmed the stability of this complex (RMSD < 1 nm). In the mouse periodontitis model, topical application of CLEO at 3 and 4 mg/mL significantly reduced gingival inflammation, alveolar bone resorption, and the number of TRAP-positive osteoclasts compared with the vehicle-treated periodontitis group (all p < 0.05). Furthermore, CLEO treatment dose-dependently lowered serum MMP-9 levels (from 24.15 ± 0.24 pg/mL in the model group to 12.36 ± 0.54 pg/mL in the high-dose group) and COX-2 levels (from 15.38 ± 0.62 pg/mL to 8.99 ± 0.57 pg/mL). The therapeutic efficacy of the high-dose CLEO group was comparable to that of the 2% minocycline group. CLEO exerts anti-P. gingivalis and anti-biofilm effects in vitro and ameliorates periodontitis in vivo through multi-target mechanisms, providing pharmacological evidence for its traditional use in inflammatory conditions.