基于网络药理学探讨参柴颗粒保肝护肝作用的主要成分和靶点

Discussion on the Major Ingredients and Targets of Shenchai Granules for the Hepatoprotective Based on Network Pharmacology

关键词:  参柴颗粒  网络药理学  肝病  活性成分  靶点

Key words:  Shenchai granules  network pharmacology  liver diseases  active ingredients  targets

摘要:

目的 对参柴颗粒进行网络药理学研究，以探讨其保肝护肝的作用机制。方法 利用TCMSP和TCM Database@Taiwan数据库并结合药动学参数对参柴颗粒中的活性成分进行筛选，结合成分及疾病相关数据库（Drugbank、GeneCards、TTD、Pubmed和PharmGKB）对成分相关靶点进行预测，对得到的靶点进行基因功能和通路注释分析，同时构建靶点间的蛋白互作网络，筛选出核心靶点，并构建参柴颗粒成分-靶点-通路网络，探讨参柴颗粒的保肝护肝作用。结果 从参柴颗粒中共预测得到49个化合物，并筛选出了176个成分作用于肝病的相关靶点。其中槲皮素、山奈酚、黄苓苷、豆甾醇、β-谷甾醇、千层纸黄素、芒柄花黄素可能为主要的活性成分，ALB、IL-6、TNF、JUN、AKT1、TP53、VEGFA、MAPK3、SRC、PTGS2可能为保肝护肝作用的主要靶点。KEGG通路富集分析表明、参柴颗粒可能是通过调控靶点作用于肿瘤通路，乙型肝炎，丙型肝炎，非酒精脂肪肝，胰岛素抵抗，TNF、HIF-1、FoxO、PI3K-Akt、ErbB信号通路等通路发挥保肝护肝作用的。参柴颗粒成分-靶点-通路网络表明，参柴颗粒活性成分作用于多个靶点，影响不同的代谢通路、相互作用、相互协调，从而起到对肝脏的保护机制。结论 参柴颗粒可通过多成分-多靶点-多通路的调控网络发挥保肝护肝的功效，对参柴颗粒保肝护肝作用的网络药理学研究期望可以为中医药对肝病治疗的分子机制研究提供参考。

Abstract:

OBJECTIVE Network pharmacology strategy was applied to study the hepatoprotective effect and underlying mechanisms of Shenchai Granules(SCG). METHODS The active ingredients of SCG were selected by the TCMSP and TCM Database@Taiwan, and the related targets of these ingredients were predicted by the Drugbank, GeneCards, TTD, Pubmed and PharmGKB database. The gene ontology, KEGG pathway analysis was performed by DAVID, protein protein interaction network of the targets and ingredient-target-pathway network of SCG were also constructed. RESULTS Forty-nine ingredients were predicted from the SCG, 176 SCG ingredients related targets with hepatoprotective effect were screened from the database. Among the active ingredients, quercetin, kaempferol, baicalin, stigmasterol, β-sitosterol, oroxylin A, formononetin were the main ingredients. And ALB, IL6, TNF, JUN, AKT1, TP53, VEGFA, MAPK3, SRC, PTGS2 might be the main targets for protect effect on liver. The KEGG pathway enrichment analysis showed that SCG related targets were correlated with pathways including cancer, Hepatitis B, Hepatitis C, non-alcoholic fatty liver disease, insulin resistance, TNF, HIF-1, FoxO, PI3K-Akt, ErbB signaling pathway ect. The ingredient-target-pathway network of SCG showed that the active ingredients of SCG acted with multiple targets, affected multi-pathways, interacted and coordinated with each other, and thus played a protective role in the liver. CONCLUSION SCG serves as a multi-ingredients, multi-target, multi-pathway treatment for liver diseases. Network pharmacological study of SCG on hepatoprotective effect was expected to provide reference for the study of mechanism of traditional Chinese medicine in the treatment of liver diseases.