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. 2025 Apr 3;29(4):219.
doi: 10.1007/s00784-025-06313-5.

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

Lin-Sha Ma  1 , Xue-Ting Jia  1 , Fa-Quan Hu  2 , Yu-Jiao Zheng  2 , Xiao-Feng Huang  1 , Xiaohui Rausch-Fan  3 , Xiao-Chuan Fan  4
Affiliations

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

Lin-Sha Ma et al. Clin Oral Investig. .

Abstract

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 μg/mL. Anti-inflammatory effects were evaluated by measuring IL-1β, IL-6, and TNF-α 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-1β and IL-6, and signaling pathways, including TNF, IL-17, and HIF-1, was verified. L. barbarum extract significantly reduced IL-1β, IL-6, and TNF-α 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 relevance: L. barbarum. may serve as a natural therapeutic agent for periodontitis by modulating immune responses and targeting key inflammatory mediators and signaling pathways.

Keywords: Lycium barbarum; Experimental validation; Molecular docking; Network pharmacology; Periodontitis.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Competing interests: The authors declare no competing interests.

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