Xu Ziheng, Wang Can, Luan Zuxiang, Zhang Dapei, Dong Baiqing
School of Public Health and Management, Guang University of Chinese Medical, Nanning, Guangxi, China.
Guangxi Key Laboratory of Veterinary Biotechology, Guangxi Veterinary Research Institute, Nanning, Guangxi, China.
Front Vet Sci. 2023 Mar 23;10:1155677. doi: 10.3389/fvets.2023.1155677. eCollection 2023.
Hepatitis E is a disease of public health significance caused by the cross-species transmission of zoonotic hepatitis E virus (HEV) infection. There are no specific drugs. In this study, network pharmacology was used to reveal the mechanism of treatment of the active constituents of the Hance on hepatitis E. Based on the previously published representative components of Hance, we were screened the active components with OB ≥ 20% and DL ≥ 0.1 in Hance based on the TCMSP, predicted the target online through Swiss target prediction, and integrated the hepatitis E target in the GeneCards and DisGenet databases. Then, the core target was screened and the GO and KEGG enrichment and the network of the drug-active-ingredient-disease-pathway-target analysis were performed by the Cytoscape software. There were 11,046 hepatitis E targets, including PI3K-AKt, SRC, MAPK, PTPN11, EGFR, STAT1 and so on. The core ingredients include Oleanolic acid, Butin, β-sitosterol, Soyasapogenol E, 5,7-dihydroxy-2-methyl-8-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxychromen-4-one, Stigmasterol, Emodin, Physcion, and Enoxolone. A total of 1,410 GO enrichment results of core targets, including 1,246 biological process, 51 cell composition and 113 molecular function results. KEGG pathway was enriched in 150 related pathways, suggesting that Hance acts on cancer signaling pathway, endocrine resistance pathway, PI3K-AKt signaling pathway, MAPK, TNF and other signaling pathway. Through key components such as Oleanolic acid, Butin, β-sitosterol, Stigmasterol, and Enoxolone and other components interferes with AKT1, IL-6 and TNF, and regulates pathway in cancer, PI3K-AKt signaling pathway and MAPK pathway to play a therapeutic role in hepatitis E.
戊型肝炎是一种具有公共卫生意义的疾病，由人畜共患戊型肝炎病毒（HEV）感染的跨物种传播引起。目前尚无特效药物。本研究采用网络药理学方法揭示了虎杖活性成分治疗戊型肝炎的作用机制。基于先前发表的虎杖代表性成分，依据中药系统药理学数据库与分析平台（TCMSP）筛选出虎杖中口服生物利用度（OB）≥20%且药物相似性（DL）≥0.1的活性成分，通过瑞士靶点预测在线预测靶点，并整合了基因卡片（GeneCards）和疾病基因数据库（DisGenet）中的戊型肝炎靶点。然后，筛选出核心靶点，并利用Cytoscape软件进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析以及药物-活性成分-疾病-通路-靶点网络分析。戊型肝炎靶点有11,046个，包括磷脂酰肌醇-3激酶-蛋白激酶B（PI3K-AKt）、肉瘤病毒癌基因（SRC）、丝裂原活化蛋白激酶（MAPK）、蛋白酪氨酸磷酸酶非受体型11（PTPN11）、表皮生长因子受体（EGFR）、信号转导和转录激活因子1（STAT1）等。核心成分包括齐墩果酸、芦丁、β-谷甾醇、大豆皂醇E、5,7-二羟基-2-甲基-8-[(2S,3R,4S,5S,6R)-3,4,5-三羟基-6-(羟甲基)氧杂环己烷-2-基]氧基色原酮-4-酮、豆甾醇、大黄素、大黄酚和甘草次酸。核心靶点共有1410个GO富集结果，包括1246个生物学过程、51个细胞组成和113个分子功能结果。KEGG通路富集于150条相关通路，提示虎杖作用于癌症信号通路、内分泌抵抗通路、PI3K-AKt信号通路、MAPK、肿瘤坏死因子（TNF）等信号通路。通过齐墩果酸、芦丁、β-谷甾醇、豆甾醇和甘草次酸等关键成分干扰AKT1、白细胞介素-6（IL-6）和TNF，并调节癌症、PI3K-AKt信号通路和MAPK通路中的相关途径，从而在戊型肝炎治疗中发挥作用。
