基于生物分子网络调控研究柴芪益肝方治疗肝纤维化的作用机制

Study on the Mechanism of Chaiqi Yigan Prescription in the Treatment of Liver Fibrosis Based on Biomolecular Network Regulation

目的基于生物分子网络研究柴芪益肝方治疗肝纤维化的作用机制。方法检索TCMSP、TCMID、Swiss Target Prediction数据库,挖掘柴芪益肝方的潜在活性成分及其作用靶点,并基于OMIM和Gene Cards数据库筛选肝纤维化的相关靶点。运用String数据库和Cytoscape软件对PPI进行可视化及拓扑学分析。借助clusterprofile对交集靶点行GO分析以及KEGG富集分析,运用Autodckvina软件进行分子对接。结果筛选出柴芪益肝方137种潜在活性成分以及257个对应靶点,肝纤维化相关靶点6807个,其抗纤维化作用可能与丝裂原激活蛋白激酶MAPK1/3/8、原癌基因酪氨酸激酶Src、激活子蛋白c-Jun、热休克蛋白HSP90α、表皮生长因子受体、p53抑癌基因、血管内皮生长因子、连环蛋白β1、肝细胞生长因子等靶点有关。柴芪益肝方抗纤维化的靶点显著富集于PI3K-Akt、TNF、IL-17、MAPK/NF-κB、HIF-1α/VEGF等信号通路中。分子对接结果表明,柴芪益肝方的主要活性成分槲皮素、白藜芦醇、山柰酚、木犀草素、丹参酮ⅡA等对丝裂原激活蛋白激酶MAPK1/3/8、原癌基因酪氨酸激酶Src、激活子蛋白c-Jun、热休克蛋白HSP90α、表皮生长因子受体、p53抑癌基因、血管内皮生长因子、连环蛋白β1等靶点表现出显著性亲和作用。结论柴芪益肝方中槲皮素、白藜芦醇、山柰酚、木犀草素、丹参酮ⅡA等活性成分可能作用于丝裂原激活蛋白激酶MAPK1/3/8、原癌基因酪氨酸激酶Src、激活子蛋白c-Jun、热休克蛋白HSP90α、表皮生长因子受体、连环蛋白β1、肝细胞生长因子等靶点,参与PI3K-Akt、TNF、IL-17、MAPK/NF-κB、HIF-1α/VEGF等信号通路,调控氧化应激反应、肝脏炎症反应、肝再生等生物过程,最终发挥治疗肝纤维化的作用。

Objective To study the mechanism of Chaiqi Yigan Prescription in the treatment of liver fibrosis based on biomolecular networks.Methods Potential effective components and targets of Chaiqi Yigan Prescription were obtained from TCMSP,TCMID and Swiss Target Prediction database.The screened potential targets of Chaiqi Yigan Prescription for liver fibrosis treatment based on GeneCards and OMIM were input into String database for PPI network,and the active components-targets network of liver fibrosis was further established via Cytoscape.Finally,GO and KEGG enrichment analysis were performed using clusterprofile.Molecular docking of active components of Chaiqi Yigan Prescription on target proteins were carried out through Autodock vina.Results 137 potential active ingredients and 257 corresponding targets of Chaiqi Yigan Prescription were screened out,6807 targets related to liver fibrosis,and its anti-fibrosis effect may be related to mitogen-activated protein kinase MAPK1/3/8 and proto-oncogene tyrosine.Src,activator protein c-Jun,heat shock protein HSP90α,epidermal growth factor receptor,p53 tumor suppressor gene,vascular endothelial growth factor,cateninβ1,hepatocyte growth factor and other targets are related.The anti-fibrotic targets of Chaiqi Yigan Prescription are significantly enriched in PI3 K-Akt,TNF,IL-17,MAPK/NF-κB,HIF-1α/VEGF and other signal pathways.The molecular docking results showed that the main active components of Chaiqi Yigan Prescription,quercetin,resveratrol,kaempferol,luteolin,tanshinoneⅡA,etc.,have an effect on mitogen-activated protein kinase MAPK1/3/8 and protooncogene tyrosine kinase Src Activator protein c-Jun,heat shock protein HSP90α,epidermal growth factor receptor,p53 tumor suppressor gene,vascular endothelial growth factor,cateninβ1 and other targets showed significant affinity.Conclusion Quercetin,resveratrol,kaempferol,luteolin,tanshinoneⅡA and other active ingredients in Chaiqi Yigan Prescription may act on mitogen-activated protein kinase MAPK1/3/8,proto-oncogene tyrosine kinase Src,activation C-Jun,heat shock protein HSP90α,epidermal growth factor receptor,cateninβ1,hepatocyte growth factor and other targets,involved in PI3 K-Akt,TNF,IL-17,MAPK/NF-κB,HIF-1αSignal pathways such as VEGF regulate oxidative stress,liver inflammation,liver regeneration and other-biological processes,and ultimately play a role in the treatment of liver fibrosis.