当归改善特发性肺纤维化的分子机制：网络药理学和分子对接研究。
The molecular mechanism of Ligusticum wallichii for improving idiopathic pulmonary fibrosis: A network pharmacology and molecular docking study.
机构信息
Department of Preclinical Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, China.
出版信息
Medicine (Baltimore). 2022 Feb 11;101(6):e28787. doi: 10.1097/MD.0000000000028787.
BACKGROUND
At present, there was no evidence that any drugs other than lung transplantation can effectively treat Idiopathic Pulmonary Fibrosis (IPF). Ligusticum wallichii, or Chinese name Chuan xiong has been widely used in different fibrosis fields. Our aim is to use network pharmacology and molecular docking to explore the pharmacological mechanism of the Traditional Chinese medicine (TCM) Ligusticum wallichii to improve IPF.
MATERIALS AND METHODS
The main chemical components and targets of Ligusticum wallichii were obtained from TCMSP, Swiss Target Prediction and Phammapper databases, and the targets were uniformly regulated in the Uniprot protein database after the combination. The main targets of IPF were obtained through Gencards, OMIM, TTD and DRUGBANK databases, and protein interaction analysis was carried out by using String to build PPI network. Metascape platform was used to analyze its involved biological processes and pathways, and Cytoscape3.8.2 software was used to construct "component-IPF target-pathway" network. And molecular docking verification was conducted through Auto Dock software.
RESULTS
The active ingredients of Ligusticum wallichii were Myricanone, Wallichilide, Perlolyrine, Senkyunone, Mandenol, Sitosterol and FA. The core targets for it to improve IPF were MAPK1, MAPK14, SRC, BCL2L1, MDM2, PTGS2, TGFB2, F2, MMP2, MMP9, and so on. The molecular docking verification showed that the molecular docking affinity of the core active compounds in Ligusticum wallichii (Myricanone, wallichilide, Perlolyrine) was <0 with MAPK1, MAPK14, and SRC. Perlolyrine has the strongest molecular docking ability, and its docking ability with SRC (-6.59 kJ/mol) is particularly prominent. Its biological pathway to improve IPF was mainly acted on the pathways in cancer, proteoglycans in cancer, and endocrine resistance, etc.
CONCLUSIONS
This study preliminarily identified the various molecular targets and multiple pathways of Ligusticum wallichii to improve IPF.
背景
目前，除肺移植外，尚无其他药物可有效治疗特发性肺纤维化（IPF）。川芎，又名川穹，已广泛应用于各种纤维化领域。我们的目的是使用网络药理学和分子对接来探索中药川芎改善 IPF 的药理机制。
材料和方法
从 TCMSP、SwissTargetPrediction 和 Phammapper 数据库中获取川芎的主要化学成分和靶点，并在 Uniprot 蛋白质数据库中统一整合后进行靶点调控。通过 Gencards、OMIM、TTD 和 DRUGBANK 数据库获得 IPF 的主要靶点，并使用 String 进行蛋白质相互作用分析，构建 PPI 网络。使用 Metascape 平台分析其涉及的生物学过程和途径，并用 Cytoscape3.8.2 软件构建“成分-IPF 靶点-途径”网络。并通过 AutoDock 软件进行分子对接验证。
结果
川芎的活性成分有杨梅酮、川芎内酯、川芎嗪、蛇床子素、正丁烯基苯酞、豆甾醇和 FA。它改善 IPF 的核心靶点有 MAPK1、MAPK14、SRC、BCL2L1、MDM2、PTGS2、TGFB2、F2、MMP2、MMP9 等。分子对接验证表明，川芎中核心活性化合物（杨梅酮、川芎内酯、川芎嗪）与 MAPK1、MAPK14 和 SRC 的分子对接亲和力均<0。川芎嗪的分子对接能力最强，与 SRC 的对接能力（-6.59 kJ/mol）尤为突出。其改善 IPF 的生物途径主要作用于癌症中的途径、癌症中的蛋白聚糖和内分泌抵抗等途径。
结论
本研究初步鉴定了川芎改善 IPF 的多种分子靶点和多个途径。
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