Mechanism of Lycium barbarum in treating periodontitis based on network pharmacology, molecular docking, and experimental validation

Objective To investigate the active components of Lycium barbarum (L. barbarum) and their therapeutic role in periodontitis through network pharmacology, molecular docking, and experimental validation. Materials and methods The active ingredients and targets of L. barbarum and the targets of periodontitis were retrieved from multiple pharmaceutical databases. An L. barbarum-active ingredients-targets network diagram was constructed by Cytoscape software. A protein interaction network was constructed using the STRING platform. Hub targets were enriched using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Key periodontitis targets were analyzed using molecular docking and molecular dynamics. Raw264.7 cells were stimulated with lipopolysaccharide (LPS) and treated with L. barbarum extract at concentrations of 1, 5, and 10 mu g/mL. Anti-inflammatory effects were evaluated by measuring IL-1 beta, IL-6, and TNF-alpha levels using enzyme-linked immunosorbent assay. Osteoclast differentiation was induced for 5 d, MMP9, RANK, and TRAP mRNA expression were quantified by real-time polymerase chain reaction (RT-PCR), and osteoclast formation was confirmed via tartrate-resistant acid phosphatase (TRAP) staining. Results We identified 45 active ingredients and 205 potential targets of L. barbarum alongside 3,520 periodontitis targets. A total of 132 L. barbarum-periodontitis co-targets were identified. The hub genes of L. barbarum regulate periodontitis and have strong binding activity with active ingredients. The involvement of inflammatory factors, such as IL-1 beta and IL-6, and signaling pathways, including TNF, IL-17, and HIF-1, was verified. L. barbarum extract significantly reduced IL-1 beta, IL-6, and TNF-alpha production in LPS-stimulated Raw264.7 cells. Additionally, L. barbarum extract downregulated MMP9, RANK, and TRAP expression and inhibited osteoclast differentiation, as evidenced by the reduced number of TRAP-positive multinucleated cells. Conclusions The bioactive constituents of L. barbarum were verified to exert anti-inflammatory and osteoclastogenesis-inhibitory effects by targeting inflammatory mediators, oxidative stress, and TNF, IL-17, and HIF-1 signaling pathways, demonstrating potential therapeutic benefits for periodontitis. Clinical relevanceL. barbarum. may serve as a natural therapeutic agent for periodontitis by modulating immune responses and targeting key inflammatory mediators and signaling pathways.