Network pharmacology, molecular docking, and in vivo experiments reveal the effects of Polygonati Rhizoma on periodontitis.

This study explores Polygonati Rhizoma’s therapeutic potential against periodontitis using network pharmacology, molecular docking, and experimental validation to uncover its mechanisms. Active ingredients and targets of Polygonati Rhizoma were sourced from TCMSP and DrugBank, while periodontitis-related targets were retrieved from GeneCards, DisGeNET, and PharmGKB. Core targets were identified via Venny 2.1, and a compound-target network was built using Cytoscape. GO/KEGG analyses and molecular docking were performed. A periodontitis mouse model (C57BL/6) was treated with 500 mg/kg Polygonati Rhizoma or water (control). Post-treatment, tissues and serum were analyzed. Twelve active ingredients in Polygonati Rhizoma (e.g., diosgenin, baicalein) exerted therapeutic effects by targeting core proteins such as MMP9, PPARG, and ESR1, and modulating signaling pathways including PI3K/AKT, IL-17/TNF, and HIF-1. In vivo experiments showed that Polygonati Rhizoma significantly suppressed serum IL-6 and TNF-α levels (P < 0.01), alleviated alveolar bone resorption, and reduced inflammatory infiltration in periodontal tissues of periodontitis mice. Additionally, Polygonati Rhizoma ameliorated histopathological damage in the liver and intestine, modulated the gut microbiota structure by increasing the abundance of Prevotella, and enriched ABC transporter-related functions. Polygonati Rhizoma alleviated alveolar bone loss in a periodontitis mouse model, suppressed inflammation by targeting MMP9, PPARG, and ESR1 via the PI3K/AKT, IL-17/TNF, and HIF-1 signaling pathways, reduced the levels of pro-inflammatory cytokines (IL-6/TNF-α), and modulated the gut microbiota composition. Modulation of the gut microbiome was associated with​ attenuated systemic inflammation, suggesting a potential role in the therapeutic effects of Polygonati Rhizoma.