基于网络药理学和分子对接的补肾固齿丸治疗肾虚血热型牙周病物质基础与作用机制研究

Study on the substance basis and mechanism of Bushen Guchi Pill in the treatment of periodontal disease of kidney deficiency and blood heat type based on network pharmacology and molecular docking

关键词:  补肾固齿丸  肾虚血热型牙周病  网络药理学  分子对接  物质基础  作用机制

Key words:  Bushen Guchi Pill  kidney deficiency blood heat type periodontal disease  network pharmacology  molecular docking  physical base  mechanism of action

摘要:

[目的] 通过网络药理学及分子对接分析，揭示了补肾固齿丸治疗肾虚血热型牙周病的有效物质基础及作用机制。[方法] 通过中药系统药理学数据库与分析平台（TCMSP）等数据库及平台检索补肾固齿丸复方中各味药材的所有有效成分及相应靶标，在人类基因数据库（Gene Cards）及在线《人类孟德尔遗传》（OMIM）平台检索疾病相关靶基因，构建补肾固齿丸“活性成分-成分对应靶标-牙周病靶标”网络，进一步筛选进行网络拓扑学分析，并对有效核心成分及关键靶标进行分子对接，分析小分子配体与受体的结合能力。[结果] 筛选出12个活性成分，25个靶标，关键靶标3个，分别为雌激素受体（ESR1）、表皮生长因子受体（EGFR）、磷酸肌醇3-激酶α（PIK3CA）。这些成分及靶标基因通过对核受体活性、蛋白激酶活性、酶激活剂活性、生长因子结合、血红素结合、内肽酶活性、蛋白质同二聚活性等的调节，参与细胞肿瘤抗原（P53）及核因子κB（NF-κB）信号通路的调控过程对牙周病的治疗起到重要作用。分子对接分析发现，3个关键靶标与12个活性成分（Quercetin、Aureusidin、Physcion等）均具有一定的亲和力。[结论] 补肾固齿丸通过复杂的网络调控对肾虚血热型牙周病的起到有效治疗作用，该研究为更进一步探索其治疗相关证候的作用机制及临床应用提供了研究思路和理论基础。

Abstract:

[Objective] This study aimed to reveal the effective substance basis and mechanism of Bushen Guchi Pill in treating kidney deficiency heat type periodontitis through network pharmacology and molecular docking analysis. [Methods] All the active ingredients and corresponding targets of each medicinal material in Bushen Guchi Pill compounds were retrieved through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） and other databases and platforms. Disease-related target genes were retrieved in human gene database（GeneCards） and Online Mendelian Inheritance in Man（OMIM） databases，and the network of “active ingredient-component target-periodontal disease target” of Bushen Guchi Pill was constructed，and further screened for network topology analysis. And the effective core components and key targets of molecular were docked to analyze the binding ability of small molecular ligands to receptor. [Results] The 12 active ingredients，25 targets and 3 key targets were identified as Estrogen receptor（ESR1），Epidermal growth factor receptor（EGFR） and Phosphatidylinositol 4，5-bisphosphate 3-kinase catalytic subunit alpha isoform（PIK3CA）. These components and targets play an important role in the treatment of periodontal disease by regulating nuclear receptor activity，protein kinase activity，enzyme activator activity，growth factor binding，heme binding，endopeptidase activity，protein homo-dimerization activity，and participating in the regulation of Cellular tumor antigen（P53） and nuclear factor kappa-B（NF-κB） signaling pathway. Molecular docking analysis showed that 3 key targets had certain affinity with 12 active ingredients（Quercetin，Aureusidin，Physcion，etc.）. [Conclusion] Bushen Guchi Pill plays an effective role in the treatment of periodontal disease of kidney deficiency and blood heat type through complex network regulation. This study provides research ideas and theoretical basis for further exploring the mechanism and clinical application of its treatment-related syndromes.