基于“活性成分-靶点-通路”网络药理学,探讨蒙药四味石榴散治疗高脂血症的作用机制

Mechanism of Treating Hyperlipidemia by Siweishiliu Powder Based on Network Pharmacology

目的利用网络药理学手段预测四味石榴散作用靶点,探索其治疗高脂血症的作用机制。方法以口服生物利用度>30%及类药性>0.10为建立筛选标准,利用TCMSP数据库和化学专业数据库筛选出四味石榴散符合标准的主要活性成分;利用Swiss Target Prediction预测活性成分的潜在靶点,并于OMIM、DisGeNET、DiGSeE和GeneCard四个疾病靶点数据进行比对,获得四味石榴散治疗高血脂的潜在靶点;结合String分析靶点蛋白交互关系,采用Matascape平台对潜在靶点的GO注释和KEGG Pathway进行富集分析。利用Cytoscape软件构建四味石榴在降高血脂功效的"活性成分-作用靶点-通路"网络结构图。结果从蒙药四味石榴散中共筛选出16个高活性化合物,预测分析到35个与降高血脂相关作用靶点,主要参与了脂质合成、转运、排泄及激素水平调节等多种降血脂的生物过程,富集到31条KEGG相关通路,涉及了脂质合成及代谢通路,Th17细胞分化等免疫通路,花生四烯酸代谢等炎症通路,体现其多成分-多靶点-多通路治疗高脂血症的作用机制。结论蒙药四味石榴散可通过干预脂肪酸代谢,激素调节,免疫稳态等相关通路,起到祛巴达干赫依的作用来治疗高脂血症。

Objective To predict the target of Siweishiliu powder and explore its mechanism of treating hyperlipidemia.Methods the screening criteria were established with oral bioavailability>30%and medicinal property>0.10.The active components of Siweishiliu powder that met the screening criteria were screened from TCMSP database and chemical database.The website of Swiss Target Prediction was used to predict the potential target of the active components and compared with the four disease databese of OMIM,DisGeNET,DiGSeE and GeneCard to obtain the potential Target of Siweishiliu powder for treating hyperlipidemia.The interactive analysis of target proteins was analyzed by String website;meanwhile,The GO annotation and KEGG Pathway enrichment analysis of potential targets were conducted by Matascape platform.Cytoscape software was used to draw the network structure diagram of"ingredients-targets-pathways"of Siweishiliu powder in treating hyperlipidemia.Results From Siweishiliu powder,a total of 16 compounds with high activity were screened out,and 35 targets related to lowering hyperlipidemia were predicted and analyzed,which were mainly involved in the biological processes of lipid synthesis,transport,excretion and hormone levels regulation.Thirty-one kegg pathways were enriched,including fatty acid metabolism pathways,Th17 cell differentiation and other immune pathways,arachidonic acid metabolism and other inflammatory pathways,reflecting the mechanism of its multi-component,multi-target and multi-pathway in the treatment of hyperlipidemia.Conclusion Siweishiliu powder may play the role of removing badakan heyi by regulating fatty acid metabolism,hormone regulation,immune homeostasis or other pathways to cure hyperlipidemia.