基于中药网络药理学及分子对接研究红花防治肝纤维化的成分与作用机制

Based on the Pharmacology and Molecular Docking of Traditional Chinese Medicine Network, the Components and Mechanism of Action of Safflower in the Prevention and Treatment of Liver Fibrosis Were Studied

目的:基于中药网络药理学原理,探究红花防治肝纤维化的主要活性成分与作用靶点。方法:通过GeneCards数据库搜集肝纤维化治疗靶点;根据TCMSP数据库获得红花含有的活性成分,并利用PubChem、Swiss Target Prediction数据库预测活性成分作用的靶蛋白,找到红花与肝纤维化的共同靶点,构成Venn图;采用Cytoscape 3.9.1软件构建“红花–成分–靶点”网络;基于string数据库绘制蛋白互作网络(PPI)并进行GO和KEGG富集分析,选取重要成分和关键靶点进行分子对接。结果:从红花中筛选出Baicalein (黄芩苷)、Luteolin (木犀草素)、6-Hydroxykaempferol (6-羟基山奈酚)、Quercetagetin (槲皮素)、Kaempferol (山奈酚)等20个活性成分,这些有效成分可能通过调节AKT1、TNF、SRC、EGFR、CASP3等91个潜在靶蛋白,而发挥防治肝纤维化作用,涉及癌症的通路、脂质和动脉粥样硬化、EGFR酪氨酸激酶抑制剂耐药、内分泌抵抗、乙型肝炎等152条通路。分子对接显示重要成分和关键靶点对接良好。结论:中药红花中的多种成分可作用多个靶点,通过多条通路防治肝纤维化。

Objective: To explore the main active components and targets of safflower in the prevention and treatment of liver fibrosis based on the pharmacological principles of traditional Chinese medi-cine networks. Methods: Liver fibrosis therapeutic targets were collected through the GeneCards database. According to the TCMSP database, the active ingredients contained in safflower were obtained, and the target proteins of the active ingredients were predicted by PubChem and Swiss Target Prediction databases to find the common targets of safflower and liver fibrosis, which constituted a Venn chart. Cytoscape 3.9.1 software was used to build a “safflower-ingredient-target” network;Based on the string database, the protein interaction network (PPI) was plotted and the GO and KEGG enrichment analysis was carried out, and important components and key targets were selected for molecular docking. Results: 20 active ingredients such as Baicalein, Luteolin, 6-hydroxyKaempferol, Quercetagetin, and Kaempferol were screened from safflower, which may play a role in preventing and treating liver fibrosis by regulating 91 potential target proteins such as AKT1, TNF, SRC, EGFR, CASP3, etc., involving cancer pathways, lipids and atherosclerosis, EGFR tyrosine kinase inhibitor resistance, endocrine resistance, hepatitis B and other 152 pathways. Molecular docking shows that important components and key targets are well connected. Conclusions: A variety of components in traditional Chinese medicine safflower can act on multiple targets to prevent and treat liver fibrosis through multiple pathways.