Luo Yu, Liu Changyue, Liu Jiaming, Wang Huabing, Fu Yanzhen, Liu Ying
Department of Stomatology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.
Department of Stomatology, North Sichuan Medical College, Nanchong, China.
Medicine (Baltimore). 2025 May 16;104(20):e42466. doi: 10.1097/MD.0000000000042466.
This study explores the mechanism of Liuwei Dihuang Pill (LWDHP) in the treatment of periodontitis using network pharmacology and molecular docking. The active ingredients and targets of LWDHP were obtained from databases such as Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. Databases such as GeneCards, OMIM, and DisGeNET were used to obtain the relevant targets related to periodontitis. The intersection of these 2 groups of targets was taken and imported into STRING to facilitate the acquisition of protein-protein interaction data, which was then imported into Cytoscape 3.10.2 to perform topological analysis to obtain the core targets. Gene ontology and Kyoto encyclopedia of genes and genomes bioinformatics enrichment analyses of the intersecting targets were performed using the DAVID database. Validation of molecular docking matching between key active ingredients with top 5 degree values and key targets with top 5 degree values in the treatment of periodontitis with LWDHP using AutoDockTools-1.5.6. A total of 69 active ingredients were discerned in LWDHP, implicating 198 periodontitis-relevant targets. Thirty-four core targets were obtained by protein-protein interaction network topology analysis, among which the key targets with the top 5 values of degree were tumor necrosis factor (TNF), serine/threonine protein kinase AKT1, sarcoma, epidermal growth factor receptor, and matrix metallopeptidase 9. Topological analysis revealed that the key active ingredients with the top 5 values of degree in LWDHP were Polyporenic acid C, Alisol B, Hydroxygenkwanin, Denudatin B, and Kadsurenone. The molecular docking results demonstrated that the binding energies of the above molecules with targets were all <-5 kcal/mol, indicating a good binding ability between these molecules. The gene ontology enrichment results indicated that the treatment of periodontitis by LWDHP was mainly related to the inflammatory response, positive regulation of phosphatidylinositol-3-kinase-Akt (PI3K-Akt) signal transduction and other processes. Analysis of the Kyoto encyclopedia of genes and genomes signaling pathway showed that the TNF signaling pathway, the PI3K-Akt signaling pathway, and so on are important signaling pathways. In conclusion, the mechanism of action of LWDHP in the treatment of periodontitis is characterized by multicomponents, multi-targets, and multi-pathways. TNF, serine/threonine protein kinase AKT1, sarcoma, epidermal growth factor receptor, and matrix metallopeptidase 9 are the key targets and the TNF signaling pathway, the PI3K-Akt signaling pathway are the key pathways. LWDHP treats periodontitis through actions such as anti-inflammatory and regulation of the balance between osteogenesis and bone destruction.
本研究运用网络药理学和分子对接技术，探索六味地黄丸（LWDHP）治疗牙周炎的作用机制。从中药系统药理学数据库与分析平台等数据库获取LWDHP的活性成分和靶点。利用GeneCards、OMIM和DisGeNET等数据库获取与牙周炎相关的靶点。取这两组靶点的交集并导入STRING以获取蛋白质-蛋白质相互作用数据，然后将其导入Cytoscape 3.10.2进行拓扑分析以获得核心靶点。使用DAVID数据库对交集靶点进行基因本体论和京都基因与基因组百科全书生物信息学富集分析。使用AutoDockTools-1.5.6验证LWDHP治疗牙周炎时，度数排名前5的关键活性成分与度数排名前5的关键靶点之间的分子对接匹配情况。在LWDHP中共识别出69种活性成分，涉及198个与牙周炎相关的靶点。通过蛋白质-蛋白质相互作用网络拓扑分析获得34个核心靶点，其中度数排名前5的关键靶点为肿瘤坏死因子（TNF）、丝氨酸/苏氨酸蛋白激酶AKT1、肉瘤、表皮生长因子受体和基质金属蛋白酶9。拓扑分析显示，LWDHP中度数排名前5的关键活性成分是猪苓酸C、泽泻醇B、羟基芫花素、去甲淫羊藿素和海风藤酮。分子对接结果表明，上述分子与靶点的结合能均＜-5 kcal/mol，表明这些分子之间具有良好的结合能力。基因本体论富集结果表明，LWDHP治疗牙周炎主要与炎症反应、磷脂酰肌醇-3-激酶-蛋白激酶B（PI3K-Akt）信号转导的正向调节等过程有关。京都基因与基因组百科全书信号通路分析表明，TNF信号通路、PI3K-Akt信号通路等是重要的信号通路。总之，LWDHP治疗牙周炎的作用机制具有多成分、多靶点、多途径的特点。TNF、丝氨酸/苏氨酸蛋白激酶AKT1、肉瘤、表皮生长因子受体和基质金属蛋白酶9是关键靶点，TNF信号通路、PI3K-Akt信号通路是关键途径。LWDHP通过抗炎和调节成骨与骨破坏之间的平衡等作用来治疗牙周炎。
