National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Beijing, China.
Front Cell Infect Microbiol. 2024 Sep 13;14:1458913. doi: 10.3389/fcimb.2024.1458913. eCollection 2024.
Hepatocellular carcinoma (HCC) is a pressing global issue, with Hepatitis B virus (HBV) infection remaining the primary. Emodin, an anthraquinone compound extracted from the natural plant's. This study investigates the molecular targets and possible mechanisms of emodin in treating HBV-related HCC based on network pharmacology and molecular docking and validates the screened molecular targets through experiments.
Potential targets related to emodin were obtained through PubChem, CTD, PharmMapper, SuperPred, and TargetNet databases. Potential disease targets for HBV and HCC were identified using the DisGeNET, GeneCards, OMIM, and TTD databases. A Venn diagram was used to determine overlapping genes between the drug and the diseases. Enrichment analysis of these genes was performed using GO and KEGG via bioinformatics websites. The overlapping genes were imported into STRING to construct a protein-protein interaction network. Cytoscape 3.9.1 software was used for visualizing and analyzing the core targets. Molecular docking analysis of the drug and core targets was performed using Schrodinger. The regulatory effects of emodin on these core targets were validate through experiments.
A total of 43 overlapping genes were identified. GO analysis recognized 926 entries, and KEGG analysis identified 135 entries. The main pathways involved in the KEGG analysis included cancer, human cytomegalovirus infection and prostate cancer. The binding energies of emodin with HSP90AA1, PTGS2, GSTP1, SOD2, MAPK3, and PCNA were all less than -5 kcal/mol. Compared to normal liver tissue, the mRNA levels of XRCC1, MAPK3, and PCNA were significantly elevated in liver cancer tissue. The expression levels of XRCC1, HIF1A, MAPK3, and PCNA genes were closely related to HCC progression. High expressions of HSP90AA1, TGFB1, HIF1A, MAPK3, and PCNA were all closely associated with poor prognosis in HCC. experiments demonstrated that emodin significantly downregulated the expression of HSP90AA1, MAPK3, XRCC1, PCNA, and SOD2, while significantly upregulating the expression of PTGS2 and GSTP1.
This study, based on network pharmacology and molecular docking validation, suggests that emodin may exert therapeutic effects on HBV-related HCC by downregulating the expression of XRCC1, MAPK3, PCNA, HSP90AA1, and SOD2, and upregulating the expression of PTGS2 and GSTP1.
肝细胞癌（HCC）是一个紧迫的全球问题，乙型肝炎病毒（HBV）感染仍然是主要原因。大黄素是一种从天然植物中提取的蒽醌类化合物。本研究基于网络药理学和分子对接技术，探讨大黄素治疗乙型肝炎病毒相关 HCC 的分子靶点和可能机制，并通过实验验证筛选出的分子靶点。
通过 PubChem、CTD、PharmMapper、SuperPred 和 TargetNet 数据库获得与大黄素相关的潜在靶点。通过 DisGeNET、GeneCards、OMIM 和 TTD 数据库确定与 HBV 和 HCC 相关的潜在疾病靶点。使用 Venn 图确定药物和疾病之间的重叠基因。通过生物信息学网站对这些基因进行 GO 和 KEGG 富集分析。将重叠基因导入 STRING 构建蛋白质-蛋白质相互作用网络。使用 Cytoscape 3.9.1 软件可视化和分析核心靶点。使用 Schrodinger 对药物和核心靶点进行分子对接分析。通过实验验证大黄素对这些核心靶点的调控作用。
共鉴定出 43 个重叠基因。GO 分析识别出 926 项，KEGG 分析识别出 135 项。KEGG 分析主要涉及癌症、人巨细胞病毒感染和前列腺癌等途径。大黄素与 HSP90AA1、PTGS2、GSTP1、SOD2、MAPK3 和 PCNA 的结合能均小于-5 kcal/mol。与正常肝组织相比，肝癌组织中 XRCC1、MAPK3 和 PCNA 的 mRNA 水平显著升高。XRCC1、HIF1A、MAPK3 和 PCNA 基因的表达水平与 HCC 的进展密切相关。HSP90AA1、TGFB1、HIF1A、MAPK3 和 PCNA 的高表达均与 HCC 的不良预后密切相关。实验表明，大黄素可显著下调 HSP90AA1、MAPK3、XRCC1、PCNA 和 SOD2 的表达，同时显著上调 PTGS2 和 GSTP1 的表达。
本研究基于网络药理学和分子对接验证，表明大黄素可能通过下调 XRCC1、MAPK3、PCNA、HSP90AA1 和 SOD2 的表达，上调 PTGS2 和 GSTP1 的表达，对乙型肝炎病毒相关 HCC 发挥治疗作用。
