基于网络药理学研究扶正化瘀方抗肝纤维分子机制

Study on the Molecular Mechanism of Fuzheng Huayu Prescription Against Liver Fiber Based on Network Pharmacology

目的:基于网络药理学方法分析扶正化瘀方抗肝纤维化分子机制研究。方法:利用OMIM、GeneCards等数据库获得肝纤维化相关靶点,采用Venn图对扶正化瘀方活性成分作用靶点和肝纤维化相关靶点进行交互处理;利用String数据库和metascape数据库对交互靶点进行基因和信号通路注释,明确扶正化瘀方抗肝纤维化的分子机制。结果:选择了扶正化瘀方中的抗肝纤维化成分:有桃仁中的苦杏仁苷、丹参中的丹酚酸B和虫草菌丝中的虫草等。其中丹参主要化学成分为水溶性成分(丹参素、丹酚酸A及B、迷迭香酸、原儿茶酸、原儿茶醛等)和脂溶性成分(二氢丹参酮I、丹参酮IIA等)。丹参酮类是丹参的主要脂溶性成分,主要包括TanⅡA、隐丹参酮(cryptotanshinone,CPT)、丹参酮Ⅰ、二氢丹参酮等。TanⅡA是含量最多、目前研究最为深入的丹参酮。TanⅡA属二萜醌类化合物,具有抗炎、抗肿瘤、心血管保护等多种活性。通过TCMSP数据库对扶正化瘀方的这些活性成分进行筛选,并获得扶正化瘀方活性成分作用靶点。将获得的作用靶点,通过UniProt数据库将其转换为基因名,并将其导入String数据库获得作用靶点互作数据,利用Cyctoscape3.4.0构建互作网络。通过OMIM、GeneCards数据库获得肝纤维化相关靶点蛋白,对化合物靶点与肝纤维化靶点进行交互处理,获得重叠靶点。结论:体现了扶正化瘀方多靶点-多通路的作用特点,其所作用的多条通路均存在关联性,为进一步研究提供了良好的基础。

Objective: To analyze the molecular mechanism of Fuzheng Huayu prescription against liver fibrosis based on network pharmacology. Methods: Using OMIM, GeneCards and other databases to obtain liver fibrosis related targets, Venn diagram was used to interact the action targets of the active components of Fuzheng Huayu prescription and liver fibrosis related targets;using String database and metascape database to annotate the genes and signal pathways of the interactive targets, and clarify the molecular mechanism of Fuzheng Huayu prescription against liver fibrosis. Results: The anti-liver fibrosis components in Fuzheng Huayu prescription were selected:including amygdalin in peach kernel, salvianolic acid B in salvia miltiorrhiza and cordyceps sinensis in cordyceps mycelium. The main chemical components of salvia miltiorrhiza are water-soluble components(tanshinol, salvianolic acids A and B, rosmarinic acid,protocatechuic acid, protocatechuic aldehyde, etc.) and fat soluble components(dihydrotanshinone I, tanshinone IIA, etc.). Tanshinones are the main fat soluble components of salvia miltiorrhiza, mainly including Tan IIA, cryptotanshinone(CPT), tanshinone Ⅰ,dihydrotanshinone, etc. Tan IIA is tanshinone with the most content and the most in-depth research at present. Tan IIA is a diterpene quinone compound, which has many activities, such as anti-inflammatory, anti-tumor, cardiovascular protection and so on. These active components of Fuzheng Huayu prescription were screened through TCMSP database, and the action targets of the active components of Fuzheng Huayu prescription were obtained. The obtained action target is converted into gene name through UniProt database, and it is imported into String database to obtain action target interaction data, and the interaction network is constructed by using Cyctoscape3.4.0.The target proteins related to liver fibrosis were obtained from OMIM and GeneCards databases, and the compound targets were interacted with liver fibrosis targets to obtain overlapping targets. Conclusion: This study reflects the characteristics of Fuzheng Huayu prescription’s multi-target and multi-channel action, and its multiple pathways are related, which provides a good basis for further research.