Zhao Mengyuan, Fu Yun, Liu Lili, Hou Yong, Shi Mei, Zhou Hao, Zhang Guoliang
Anhui University of Chinese Medicine, Hefei, China.
Department of Infectious Disease, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, China.
Evid Based Complement Alternat Med. 2022 Mar 27;2022:5399766. doi: 10.1155/2022/5399766. eCollection 2022.
Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) has poor prognosis and high mortality rate. Curcumae Rhizoma, a classic Chinese medicinal herb, is often used to treat tumors.
Active ingredients of Curcumae Rhizoma were extracted from the Traditional Chinese Medicine Database and Analysis Platform (TCMSP) database, and potential targets were predicted by the TCMSP database and Swiss Target Prediction database. The key drug targets were filtered by intersecting predicted targets, DEGs, and genes in important modules from WGCNA. Besides, the key drug targets were used to construct a network of "herb-active ingredient-target-disease" interactions and subjected to enrichment analysis and protein-protein interaction (PPI) analysis. The hub targets based on PPI analysis was evaluated by the KMplotter database.
Three active ingredients of Curcumae Rhizoma were collected with OB ≥ 30% and DL ≥ 0.18, including hederagenin, wenjine, and bisdemethoxycurcumin. The key drug targets were mainly enriched in cell cycle checkpoint, DNA integrity checkpoint, and peptidyl-serine modification. Besides, Curcumae Rhizoma treatment of HBV-related HCC mainly involved the p53 signaling pathway and arachidonic acid metabolism. Finally, ESR1 and PTGS2 were identified as hub targets from PPI analysis. ESR1 was found to be correlated with survival in liver cancer patients with hepatitis.
Based on WGCNA and network pharmacological analysis, our results illustrated that Curcumae Rhizoma might work through regulating multitargets and multipathways in HBV-related HCC.
乙型肝炎病毒（HBV）相关的肝细胞癌（HCC）预后较差，死亡率较高。莪术是一种经典的中药材，常用于治疗肿瘤。
从中药系统药理学数据库与分析平台（TCMSP）数据库中提取莪术的活性成分，并通过TCMSP数据库和瑞士靶点预测数据库预测潜在靶点。通过将预测靶点、差异表达基因（DEGs）和加权基因共表达网络分析（WGCNA）重要模块中的基因进行交集筛选关键药物靶点。此外，利用关键药物靶点构建“药物-活性成分-靶点-疾病”相互作用网络，并进行富集分析和蛋白质-蛋白质相互作用（PPI）分析。基于PPI分析的枢纽靶点通过KMplotter数据库进行评估。
收集到3种口服生物利用度（OB）≥30%且类药性（DL）≥0.18的莪术活性成分，包括常春藤皂苷元、温郁金碱和双去甲氧基姜黄素。关键药物靶点主要富集在细胞周期检查点、DNA完整性检查点和肽基丝氨酸修饰。此外，莪术治疗HBV相关HCC主要涉及p53信号通路和花生四烯酸代谢。最后，通过PPI分析确定雌激素受体1（ESR1）和环氧合酶-2（PTGS2）为枢纽靶点。发现ESR1与肝炎肝癌患者的生存相关。
基于WGCNA和网络药理学分析，我们的结果表明莪术可能通过调节HBV相关HCC中的多靶点和多通路发挥作用。
