基于网络药理学及实验验证探讨黄连对牙周炎干预效应的作用机制OA

Aim:To investigate the potential molecular targets and mechanisms by which the traditional Chinese medi-cine Coptidis Rhizoma exerts intervention effect on periodontitis,with a focus on its regulation of inflammation and alveolar bone resorption.Methods:Active components and their potential targets were screened using a traditional Chinese medicine systems pharmacology database.A drug-target-disease network was constructed,followed by protein-protein interaction analy-sis and functional enrichment analysis.Molecular docking was performed to evaluate the binding capacity of active com-pounds to core target proteins.Publicly available single-cell RNA sequencing datasets of human gingival tissues were ana-lyzed to identify the cellular sources of target genes.A ligature-induced periodontitis(LIP)mouse model was established,and mice were randomly assigned to 4 groups:normal control,LIP,normal control+Coptidis Rhizoma,and LIP+Coptidis Rhizoma(n=6 per group).Alveolar bone resorption,osteoclast formation,and the expressions of inflammation-related genes were assessed by Micro-CT,histological staining,and quantitative real-time PCR.Results:A total of 13 active components of Coptidis Rhizoma and 118 periodontitis-related targets were identified,with MMP-9 located at the core of the protein-pro-tein interaction network.Molecular docking showed that berberine,palmatine,quercetin,etc exhibited stable binding to the catalytic site of MMP-9.Single-cell RNA sequencing analysis indicated that MMP-9 was predominantly expressed in gingival macrophages.In vivo experiments showed that the number of osteoclasts in the gingival tissue of mice in the LIP group was increased,the distance from the cementoenamel junction to the alveolar bone crest(CEJ-ABC)was enlarged,and the mRNA expression levels of Tmf,Mmp9,Il17 and Il1 b were upregulated,while in the LIP+Coptidis Rhizoma group,CEJ-ABC was reduced,and the mRNA expression levels of Tmf,Mmp-9,Il17 and Il1 b were downregulated(all P＜0.05).Conclusion:Coptidis Rhizoma may alleviate periodontal inflammation and alveolar bone resorption by modulating MMP-9-related inflam-matory pathways.