基于生物信息学分析和体外验证的黄芩抗牙周炎作用机制的初步探讨
Preliminary investigation on the mechanism of anti-periodontitis effect of Scutellariae Radix based on bioinformatics analysis and in vitro verification.
发表日期:2024 Aug 30
作者:
Jixian Feng, Yan Li, Juan Liu, Ningli Li, Bin Sun, Shizhen Zhao, Yuankun Zhai
来源:
Stem Cell Research & Therapy
摘要:
探讨黄芩抗牙周炎的物质基础、作用靶点及分子机制,为临床应用提供理论依据。黄芩的活性成分及作用靶点均从中药系统药理学数据库与分析平台(TCMSP)数据库中获取,并通过通过将在线人类孟德尔遗传(OMIM)、治疗目标数据库(TTD)、基因卡和基因表达综合(GEO)数据库整合在一起收集牙周炎相关目标。从两个目标集的交集中获得黄芩抗牙周炎的潜在目标。 Metascape数据库用于基因本体(GO)术语富集和京都基因和基因组百科全书(KEGG)通路富集分析。 Discovery Studio 软件用于关键靶标和化合物之间的分子对接,以评估它们的结合亲和力。采用 Western blot 检测 PTGS2 和 MMP9 的表达,验证黄芩主要活性化合物黄芩素对脂多糖(LPS)诱导的炎症环境下培养的人牙周膜干细胞(hPDLSCs)的调节作用。 15确定了黄芩的活性化合物和 53 个治疗牙周炎的常见靶点。其中,10个核心靶点为AKT1、IL-6、TNF、VEGFA、TP53、PTGS2、CASP3、JUN、MMP9和HIF1A。 GO和KEGG分析主要集中在对LPS的反应和癌症中的通路。分子对接表明主要活性化合物与关键靶点具有良好的结合亲和力。细胞实验证实黄芩素可干扰促炎因子PTGS2和MMP9蛋白的表达,发挥抗炎作用。本研究初步分析了黄芩抗牙周炎的作用机制,为黄芩的利用及牙周炎的治疗提供了新思路。开发用于临床治疗牙周炎的新药。© 2024 由 Elsevier Ltd 出版。
To investigate the material basis, targets and molecular mechanism of Scutellariae Radix against periodontitis to provide theoretical basis for clinical applications.The active compounds and targets of Scutellariae Radix were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database, and the periodontitis-related targets were collected by integrating Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), Genecards and Gene Expression Omnibus (GEO) database together. The potential targets of Scutellariae Radix against periodontitis were obtained from the intersection of two target sets. Metascape database was used for Gene Ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Discovery Studio software was used for molecular docking between key targets and compounds to evaluate their binding affinity. Western blot was used to check the expression of PTGS2 and MMP9 to verify the regulatory effects of baicalein, the main active compound of Scutellariae Radix, on human periodontal ligament stem cells (hPDLSCs) cultured under inflammatory environment which induced by lipopolysaccharide (LPS).15 active compounds of Scutellariae Radix and 53 common targets for periodontitis treatment were identified. Among these targets, the 10 core targets were AKT1, IL-6, TNF, VEGFA, TP53, PTGS2, CASP3, JUN, MMP9 and HIF1A. GO and KEGG analysis mainly focused on response to LPS and pathways in cancer. Molecular docking showed that the main active compounds had good binding affinity with key targets. Cell experiments confirmed that baicalein can interfere the expression of pro-inflammatory factors PTGS2 and MMP9 proteins and exert anti-inflammatory effects.Current study preliminarily analyzed the mechanism of Scutellariae Radix against periodontitis, which provide a new idea for the utilization of Scutellariae Radix and the development of novel medicine for the clinical treatment of periodontitis.© 2024 Published by Elsevier Ltd.