基于网络药理学及分子对接探讨黄精治疗黄褐斑作用机制

Discussion on Mechanism of Polygonati Rhizoma in Treating Chloasma Based on Network Pharmacology and Molecular Docking

目的:基于网络药理学及分子对接探讨黄精治疗黄褐斑的作用机制。方法:检索中药系统药理数据库和分析平台(TCMSP)数据库筛选黄精有关活性成分,利用SwissTargetPrediction预测有效成分作用靶点。通过GeneCard、Drugbank数据库收集黄褐斑相关的疾病靶点,并通过韦恩图对有效成分靶点和疾病靶点进行交集,获得黄精治疗黄褐斑的潜在有效靶点。绘制活性成分与潜在有效靶点的网络图,利用Cytoscape软件分析每个活性成分在治疗黄褐斑中的重要性。将黄精和疾病的交集靶点利用STRING数据库进行蛋白互作分析,筛选出黄精治疗黄褐斑的关键靶点。通过David数据库将交集靶点进行基因本体论(GO)功能分析和京都基因与基因组百科全书(KEGG)通路富集分析,并深度挖掘黄精主要活性成分及作用靶点;通过分子对接验证活性成分和作用靶点蛋白之间的分子结合能。结果:共筛选出黄精活性成分12个,黄精治疗黄褐斑靶点327个。黄精治疗黄褐斑的核心活性成分有(2R)-7-羟基-2-(4-羟苯基)-4-苯丙二氢呋喃、甘草素、4,5-二羟基黄酮、黄芩素、谷甾醇、西伯利亚蓼苷A、中华蓼素1、β-谷甾醇等,核心靶点为细胞周期蛋白A2 (CCNA2)、细胞周期蛋白A1 (CCNA1)、细胞周期蛋白B1 (CCNB1)、细胞周期蛋白E1 (CCNE1)、细胞周期蛋白依赖性激酶2 (CDK2)、极光激酶A (AURKA)。黄精治疗黄褐斑的通路主要富集于孕酮介导的卵母细胞成熟、细胞衰老、乙型肝炎、癌症通路等信号通路。分子对接发现活性成分和治疗靶点具有较强的结合力。结论:黄精可能通过(2R)-7-羟基-2-(4-羟苯基)-4-苯丙二氢呋喃、甘草素、4,5-二羟基黄酮等成分作用于CCNA2、CCNE1、CDK2、CCNA1、CCNA1等靶点,通过调节孕酮介导的卵母细胞成熟、细胞衰老、乙型肝炎等相关信号通路治疗黄褐斑。

Objective:To discuss the mechanism of Polygonati Rhizoma in treating chloasma based on network pharmacology and molecular docking.Methods:Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)was retrieved to screen for active ingredients related to Polygonati Rhizoma,and SwissTargetPrediction was used to predict the target action of effective ingredients. The disease targets related to chloasma were collected through the GeneCard,Drugbank database, and the potential effective targets for the treatment of chloasma by intersectingeffective ingredient targets and disease targets were obtained through Venn diagrams. A networkdiagram of active ingredients and potential effective targets was drawn, and Cytoscape software wasused to analyze the importance of each active ingredient in the treatment of chloasma. The STRINGdatabase was used to analyze protein-protein interactions between the intersection targets of PolygonatiRhizoma and diseases, and the key targets of Polygonati Rhizoma in the treatment of chloasma werescreened. The David database was performed to conduct the enrichment analysis on intersection targetson Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway,and the mainactive ingredients and target proteins of Polygonati Rhizoma were deeply explored. The molecular bindingenergy between the active ingredients and target proteins was verified through molecular docking.Results: A total of 12 active ingredients of Polygonati Rhizoma were selected, and 327 targets ofPolygonati Rhizoma for chloasma were identified. The core active ingredients of Polygonati Rhizoma intreating chloasma included (2R) -7-hydroxy-2- (4-hydroxyphenyl) -4-phenylpropanedihydrofuran,glycyrrhizin, 4,5-dihydroxyflavones, scutellarin, sitosterol, sibiricoside A, and Zhonghualiaoine 1, β-sitosterol, and the core targets included cyclin A2 (CCNA2), cyclin A1 (CCNA1), cyclin B1 (CCNB1),cyclin E1 (CCNE1), cyclin dependent kinase 2 (CDK2), and aurora kinase A (AURKA). The pathway ofPolygonati Rhizoma in treating chloasma was mainly enriched in progesterone mediated signalingpathways such as oocyte maturation, cell aging, hepatitis B, and cancer. Molecular docking revealedstrong binding affinity between active ingredients and targets. Conclusion: Polygonati Rhizoma may acton targets such as CCNA2,CCNE1,CDK2,CCNA1,and CCNA1 through components such as (2R) -7-hydroxy-2- (4-hydroxyphenyl) -4-phenylpropanedihydrofuran,glycyrrhizin,and 4,5-dihydroxyflavones,and treat chloasma by regulating progesterone mediated signaling pathways such as oocyte maturation,cell aging,and hepatitis B.